A6 Research - Healthcare and Biotechnology

October - American Pharmacist Month

2018-10-01T17:05:00.000-04:00

Value of Medical Innovation

2017-08-08T19:17:00.000-04:00

Proteon Therapeutics - Vonapanitase: A potenial for AVF Hemodialysis Patients

2016-09-23T09:00:00.000-04:00

Written by: Shruti Desai (@shrutidesai99)

Proteon (NASDAQ: PRTO) is a biopharmaceutical company developing a therapy for patients with hemodialysis. Proteon has leading drug candidate in pipeline, VONAPANITASE (PRT-201). It is a therapeutic drug that inhibits the obstruction of the surgical AVF.

ACCESS POINTS FOR HEMODIALYSIS

Long term hemodialysis requires permanent access point to bloodstream.

Vascular access points: Arteriovascular fistula (AVF) and Arteriovascular graft (AVG)

Proteon R&D Presentation

WHAT IS AVF?

Arteriovenous Fistulas, a surgical procedure, are connections between blood vein to artery to increase the blood flow. This procedure allows an easy access to filter blood during hemodialysis. However, this surgical attachment causes injury to the vessel and causing narrowing of the vessel (patency loss) which reduces the flow of blood and also creates new vessels and also prevent hemodialysis. Typically, patency loss can occur in half of the patients within one year of surgical AVF. It is important to reduce/reverse AVF loss. Patency loss requires angioplasty and missing hemodialysis appointments.

WHAT IS PAD? (Secondary Indication)

Peripheral Artery Disease is a disease in which plaque builds up in the arteries causing occlusion and harder for blood to flow smoothly. Plaque can be a combination of cholesterol, fat, fibrous tissue, and other substances. Eventually, the plaque gets harder that narrows the vessels and decrease blood flow, decrease oxygen and increase pressure in arteries and/or veins.

MARKET POTENTIAL

Recent data suggests there are 20 million adults in the U.S. with some level of kidney dysfunction (also known as Chronic Kidney Disease). This disease may eventually lead to dialysis stage (also known as ESRD), which is stage 5 of CKD. Dialysis is needed when kidneys do not function (GFR <15). According to statistical data, about 600,000 adults are on dialysis. In 2012, Medicare (Part A and B) spent $44.6 million on CKD, and $28.6 million on ESRD, only. By 2050, there will be about 1.5 billion people in worldwide with CKD, and prevalence of ESRD will increase in parallel.

CURRENT TREATMENT FOR AVF

Current treatment for AVF are nonpharmacologic or invasive procedures such as forced saline flush, surgical thrombectomy, and exchange of catheter over guidewire.

VONAPANITASE (PRT-201)

Proteon Therapeutics’ Vonapanitase (PRT-201) is a recombinant human chymotrypsin-like elastase family member 1. It is administered to the surface of artery and vein

Elastin fibrin thought to attract proliferating cells
Inhibits cells from migrating to inner vessels and hindering the blockage of the vessel
Prevents artery from narrowing and obstruction of the blood flow

A multicenter, randomized, double-blind, placebo-controlled phase 1 and 2 clinical trial was completed in 2013. The trial evaluated the use of vonapanitase in patients undergoing arteriovenous graft (AVG). This is an alternative surgical procedure in patients who do not qualify for AVF. The results of the trial indicated statistically insignificant trend for AVG survival. Later, phase 2 trial was completed evaluating safety and efficacy of vonapanitase in single application administered immediately after radiocephalic or brachiocephalic AVF. This trial compared vonapanitase to placebo. Results suggest statistical significant improvement in AVF maturation at 12 weeks and “rate of corrective procedures over more than three years of follow-up. “

DRUG SAFETY

Drug side effects that were noted in trials were procedural pain, postprocedural edema, peripheral edema, sepsis, and hypoesthesia. The adverse effects of vonapanitase were consistent with CKD patients and medical events

PHASE 1 AND 2 TRIAL

“Application of human type I pancreatic elastase (PRT-201) to the venous anastomosis of arteriovenous grafts in patients with chronic kidney disease

Primary focus was safety and efficacy of the investigational drug and increase blood flow rate by increasing vein diameter. This study enrolled 89 patients. As per statistical analysis of the trial, comparing high with placebo group, the result of increasing vein diameter is statistically significant with p-value of 0.06. However, not significant with low and medium groups.
Results indicated that Intraoperative vein diameter increased by 5% (p=0.14) in placebo group compared to vonapanitase which increased diameter by 13% (p=0.01), 15% (p=0.07), and 12% (p<0.001), low, medium, and high groups, respectively. Low group received 0.01 and 0.03mg, medium group received 0.1, 0.3, 1.0mg and high group received 3.0, 6.0, and 9.0mg

PHASE 2 TRIAL

Primary focus was to evaluate the safety and efficacy of vonapanitase in patients with CKD undergoing surgical creation of an AVF (radiocephalic or brachiocephalic) for hemodialysis”
Enrolled 151 patients. It was a multicenter, randomized, double-blind, placebo-controlled clinical study. Placebo, 10 and 30mcg (1:1:1) randomization. Follow up at weeks 2,6,12 and then every 3 months. Primary endpoint of the study was to demonstrate a trend of prolonged primary patency. Secondary endpoint of the study was to unassisted maturation at 12 weeks, secondary patency, and AVF usability.
As per results and statistical analysis of primary endpoint, trend towards prolonging primary unassisted patency over three years of follow-up was statistically significant

o Primary patency (maintaining AVF access for sufficient blood flow and hemodialysis) is when partial or complete blockage of vein occur which leads to less to no blood flow and inhibiting hemodialysis. The only way to fix this occlusion is invasive procedure (surgery), but it has poor durability meaning veins can potentially block in future.

As per results and statistical analysis of secondary endpoint, improvement in secondary patency, AVF maturation at 12weeks and in rate of corrective procedure over three years of follow-up were all statistically significant

o Secondary patency (AKA AVF survival). Secondary patency loss is when procedure is done to restore AVF post primary patency loss. If a patient had secondary patency loss, then that patient can no longer fix the initial AVF. The patient either have to get a new AVF or AVG. This procedure cannot be done immediately, therefore in mean while patient undergo temporary catheter for hemodialysis.

META-ANALYSIS

“Recombinant Human Elastase Treatment of Cephalic Veins”

Goal of this study was a safety of vonapanitase and if it is applied to outflow vein during the AVF surgery could improve longevity of AVF surgery. The primary focus of the study was to investigate the pharmacology of the effective vonapanitase doses (3mcg-33mcg) on elastin of human cephalic vein. (Elastin contents are measured by desmosin content, which is protein cross linked to elastin using radioimmunoassay). As per results and statistical analysis, Mean desmosin content of vein treated with various concentrations of vonapanitase, which showed that the higher the concentration of vonapanitase, the greater the reduction of desmosin with p-value of <0.05, and p-value of <0.001 when compared to placebo. In conclusion, vonapanitase targets elastin in elastic fibers and reduces desmosin within 1-4 hours post administration

PERSONAL OPINION

My personal view on the drug is that vonapanitase has shown promising results in terms of increasing diameter of veins, prolonging primary patency, and reduction of desmosin. Additionally, vonapanitase has no other medication to compete against or to compare. It has shown significant results post single administration of the drug.

NEAR TERM CATALYST AND PRICE TARGET

Proteon is currently conducting Phase 3 (PATENCY-1 trial and PATENCY-2 trial).

PATENCY

Randomized, double blind, placebo controlled
300 patients in the US with 12 month followup
Vonapanitase 30mcg versus placebo (2:1)
Primary and Secondary endpoints being same as Phase 2 which was statistically significant.

In my opinion, Phase 3 PATENCY 1 trial should meet its primary endpoint since 3x improvement was observed in Phase 2 in radiocephalic AVFs and Phase 3 trial requires 2x improvement for p=0.0001. The PATENCY-1 should be fully enrolled in October 2015 with top line data in December 2016. In addition, PATENCY-2 should be fully enrolled in Q1 2017 with topline data in 2H 2018. As of May 9^th, 2016, Proteon Therapeutics has cash, cash equivalent ad available-for-sale investments totaled $59.4 million. According to CEO, cash is enough to fund operation until 1Q 2017.

With current market valuation and recent biotech selloff, this creates good opportunity for investor to go long PRTO with my price target of $10.53 (conservative DCF model)

REFERENCES:

Dwivedi, A.J. et al. Application of human type I pancreatic elastase (PRT-201) to the venous anastomosis of arteriovenous grafts in patients with chronic kindey disease. J Vasc Access 2014;15 (5): 376-384
Burke, S.K. et al. Vonapanitase (PRT-302, Recombinant Human Type 1Panreatic elastase. for improved arteriovenous fistula outcomes- Long Term Results
Wong et al., Recombinant Human Elastase Treatment of Cephalic Veins. Cardiovasc Pharm Open Access 2016, 5:2
Clinical Trials | Clinical Development | Proteon Therapeutics. (n.d.). Retrieved from http://www.proteontherapeutics.com/clinical-development/clinical-trials.php
National Kidney Foundation

Insmed's ARIKACE: A potential treatment for Chronic Lung Infections in Cystic Fibrosis

2015-02-20T13:00:00.000-05:00

Written by: Ankit Desai (@ankitdesai6) & Shruti Desai

Insmed (NASDAQ: INSM) is a biopharmaceutical company focused on developing inhaled therapies for patients with serious orphan lung diseases. Insmed has leading drug candidate ARIKACE^® (liposomal amikacin for inhalation) which is to treat rare lung infections due to Cystic Fibrosis and Non-tuberculosis mycobacteria.

What is Cystic Fibrosis?

Cystic Fibrosis (CF) is an autosomal recessive genetic disease that affects many organs in the body, most commonly the lungs, pancreas and sweat glands. CF is caused by mutation in a single gene on chromosome 7 which encodes for cystic fibrosis transmembrane conductance regulator also known as CFTR. These ion channels are primarily responsible for regulating the movement of chloride (Cl^-) ions across the cell surface membrane. The primary symptom of CF, resulting from abnormal transport of chloride anions in lung epithelia, is the accumulation of thick, adhesive mucous in the airway. The production of adhesive secretions leads to chronic respiratory infection then to pulmonary exacerbations and eventually respiratory failure.

Market Potential

Recent data suggests there are 30,000 adults and children in the U.S. and 70,000 patients worldwide suffering from CF. As mentioned earlier, nearly 10-20 million people in the U.S. carry the defective CFTR gene. This reflects a huge growth opportunity in the future market as new therapies are being developed. The global market size for CF was nearly $1.1 billion in 2010, which is estimated to reach $2.5 billion by 2018 (assumed growth rate of 10%). The current CF market is dominated by three major players: Novartis (TOBI inhalation solution), Genentech/Roche (Pulmozyme) and Vertex Pharmaceutical (Kalydeco).

Chronic Lung Infections in CF patients

All patients eventually develop repeated acute bacterial and viral infections that cause host inflammatory response and airway injury. There are 3 most common microorganisms: Staphylococcus aureus (also Methicillin resistant S.aureus), Haemophilus influenzae, and Pseudomonas aeruginosa (Pseudomonas). The H.influenzae is more prevalent in children (20-30%) whereas Pseudomonas is prevalent in 25% of children and >80% of adults. Since Pseudomonas is responsible for majority of chronic lung infection in CF population, most investigational drugs are being developed to eradicate Pseudomonas and prevent exacerbations.

Currently Marketed Products

Currently, there are only two FDA approved inhaled therapies for patients with chronic Pseudomonas infection: TOBI (tobramycin inhalation solution) by Novartis and Cayston (aztreonam inhalation solution) by Gilead. In clinical trials, both TOBI and Cayston have been shown to improve lung functions, respiratory symptoms and reduce hospitalizations. Both medications have its pros and cons. Cayston needs a special device and administered three times a day versus twice a day administration for TOBI. Cayston requires 3 minutes of administration time compared to 15 minutes for TOBI. There are many reasons why new inhaled treatment options for chronic Pseudomonas infections are warranted. First, some patients are not able to stay compliant with complex schedule and administration requirements. Second, some patients are not able to tolerate current treatment options due to allergic reactions or side effects.

ARIKACE:

Insmed’s Arikace (Liposomal amikacin) for inhalation is a sustained release formulation of amikacin encapsulated in liposomes.

Arikace provides:

Improved compliance (once daily dosing)
Increased efficacy (localized infiltration)\
Increased duration of effect (effects seen even after 28 day cycle)
Increased safety (due to localized effects and less drug needed to achieve same results)

In clinical studies, it has been shown to have better delivery and prolonged therapeutic effect in lungs. Insmed is currently conducting Phase 3 trials in Europe and Canada with results expected in mid-2013. In August 2011, FDA placed a clinical hold on US Phase 3 program based on review of the long-term rat inhalation carcinogenicity study. In May 2012, Insmed has reached agreement with FDA on a revised CF clinical trial population consisting of adult patients who have chronic Pseudomonas lung infections and FEV-predicted between 25% and 75%. The Company is continuing discussions with the FDA in an effort to finalize additional details of the cystic fibrosis program in the US.

Drug Safety:

Combined data from the two Phase 1/2 clinical trials (TR02-106 and TR02-105) indicated that Arikace was well tolerated and generally safe as adverse events were similarly distributed across Arikace and placebo groups. There were four discontinuations in the Arikace cohorts and one in the placebo group. Finally, it was reported that there was a trend towards mild to moderate dysphonia (8%) in the high dose Arikace group.

Phase 2 Trials:

The Phase 2 trials were carried out at 33 sites in the US and Europe were done to seek out an optimal dose of Arikace and overall safety/tolerability. Initially, trial TR02-106 included 70mg and 140mg cohorts; however DSMB review and the FDA recommended dropping lower treatment groups and continuing to monitor patients on a 1 x daily 560mg dose. Trial TR02-105 included patients treated at 280mg and 560mg doses of Arikace. All cohorts were compared to placebo.

The treatment stage for these trials was for 28 days, followed by 28 days off of treatment. Patient data was recorded weekly during the treatment stage and at days 36, 42, 49, and 56 after treatment.

As seen above, the pooled Phase 2 results showed statistically significant and clinically significant improvement in pulmonary function throughout 28 day treatment period. In addition, the effect was sustained in the off week (additional 28 days). Interestingly, one should observe the dip in mean relative change in FEV1% predicted at day 36 and 42, followed by a strong recovery by day 56 in the off treatment phase. The drop may be more indicative of the actual efficacy of Arikace, while the late recovery may just be noise in the data. It is interesting that Arikace presents this data at later presentations by removing all off treatment data except for the final day 56 data as seen below:

More encouraging data is seen in the open label extension of the TR02-105 study. In this extension, all patients randomized in the main study, who were compliant, continued to be monitored for six treatment cycles (28 days on, 56 days off) over 18 months. The data below indicates a continuous improvement in mean FEV1 % predicted vs. baseline.

While this open-label extension should be taken with a grain of salt the sustained efficacy over multiple treatment cycles is quite positive. This is primarily because the main competitors of Arikace, TOBI (Novartis) and Cayston (Gilead) appear to show diminishing improvement of FEV1% predicted over time. This is evident from the chart below, which depicts data comparing Cayston to Tobi over three treatment cycles from the Cayston Phase 3 clinical trial:

Phase 3 trial

In November 2012, Insmed has announced the completion of enrollment in the pivotal Phase 3 trial in Europe and Canada for Arikace in CF patients with Pseudomonas infection. The results are to be available in mid-2013.

There are approximately 300 patients who were randomized 1:1 to Arikace or TOBI (Novartis). It is randomized and open label study, which is appropriate since similar drug candidate are being evaluated. The Primary endpoint is relative change in FEV1 from baseline at the end of study (end of 24 weeks). In this trial, patients with history of chronic infection with pseudomonas (sputum confirmed) and FEV1≥ 25% at screening were included. This is an appropriate inclusion criterion due to increasing resistance to TOBI. According to Novartis (TOBI inhalation and TOBI Podhaler), resistance to TOBI has nearly doubled since 1999 which is nearly 85% increase. Arikace does not get inactivated by aminoglycoside-inactivating enzyme responsible for acetylation of amino group and adenylation or phosphorylation of hydroxyl group which provides a significant advantage over TOBI.

To achieve 80% power, nearly 260 patients will have to show non-inferiority to TOBI. Since TOBI only improves FEV1 by 7%, the bar is already set low to achieve non-inferiority. In Phase 2 ITT analysis, there was an average of 11% FEV1 improvement.

The reasons why I think the Phase 3 pivotal trial will succeed are:

For EMA approval, Arikace has to show non-inferiority to TOBI
Patients are allowed to continue AZI, DNAse and/or hypertonic saline which allows better baseline FEV1 analysis
Arikace is not inactivated by aminoglycoside-modifying enzyme

While I expect Arikace to display non-inferiority to TOBI (and potentially superiority) there is also good reason to believe Arikace will have commercial success. CF patients are burdened with daily administration of various therapies that can take up to 3 hours in total to complete. The 1x daily dose of Arikace requires about 13 minutes to administer compared to the 40 minutes required to complete the TOBI administration. This time doesn’t even include what is required to clean and sterilize all of the parts of the TOBI nebulizer equipment. Additionally, the nebulizer used to deliver TOBI is cumbersome, electric powered, and not discreet. The nebulizer used for Arikace delivery is battery powered and more portable, which could lead to improved compliance, a reduction in exacerbations, and in the long run a reduction in total cost of care.

Two upcoming barriers for Arikcace adoption include the eventual approval of the TOBI podhaler and the liklihood of generic TOBI in late 2014. While the TOBI podhaler is more portable and doesn’t require a power source it still requires 2 daily treatment sessions and the administration of 8 total caplets of the dry powder tobramycin formulation. Additionally, the efficacy of TOBI podhaler appeared to be slightly worse when compared to nebulized TOBI

Near term catalyst

According to the CEO, Insmed is expecting the topline Phase 3 pivotal results in mid-2013 (my prediction: July/August). They also have additional catalyst near end of 2013 which is a Phase 2 results from Non-TB mycobacteria (NTM) lung infections. In terms of Arikace’s IP and exclusivity, it has 3 orange book patents that are protected until 2029. It is also hard for generic manufacturers to manufacture liposomal product so I do not foresee any major competition from generic manufacturers.

Financial health of Insmed:

As of September 30, 2012, Insmed had total cash, cash equivalents, short-term investments, and certificate of deposits on hand totaling $91.9 million, consisting of $89.7 million in cash and short-term investments and $2.1 million in a certificate of deposit. This also include direct offering of 6.3 million shares of its common stock to Ayer Capital, RA Capital and Quaker Partners at $4.07/share. According to Whalewisdom.com the largest 13F filers holding Insmed stock include Fidelity, RA Capital, Ayer Capital, Deerfield Co., Vanguard, Blackrock, Broadfin, Palo Alto Investors and Baker Brothers Advisors.

Price Target:

$8.50*

*(Based on DCF model and conservative assumption)

Disclosure: No position – May initiate position in next 72 hours

References:

Insmed Investor Relations
31^st Annual JP Morgan Healthcare Conference (Jan 10, 2013)
PubMed
ClinicalTrial.gov
Whalewisdom.com
Cystic Fibrosis Foundation (www.cff.org)
DCF Model: Damodaran NYU Sterm School of Business, New York, NY

Top Potential Blockbuster Drugs of 2013

2013-01-15T13:41:00.003-05:00

-Shruti Desai, PharmD Candidate
A Blockbuster drug is defined as branded prescription drug that generate > $1 billion in revenue annually. They have served as catalysts for driving value within the global drug market during the past decade. Top biopharmaceutical companies have been especially reliant on developing these blockbusters for their growth; they have delivered the highest returns on R&D investments.

Despite industry concerns about fewer opportunities to develop billion dollar blockbusters, the number of drugs that reached blockbuster status has increased 6x in the past 15years – from 21 in 1995 to an estimated 123 in 2010. It seems like blockbusters have become the centerpiece of the biopharma industry, growing from 16% of global drug revenue in 1995 to 35% in 2010.

In my opinion, as science and market conditions continue to evolve and unmet needs shift to new territories, the face of the new blockbuster is likely to change again. Although 48 new drugs are expected to join the blockbuster category by 2015 the amount of revenue they generate is expected to account for less than 30% of global pharmaceutical sales.

As we have seen in many instances, a significant portion of smaller biotechnology startups ultimately get acquired by their pharma partners. However, most of these deals have happened after product launch, late in the commercial life cycle of the therapeutics. However, there is now a new business model that for pharmas to execute even earlier deals that provide full ownership for blockbusters to offset the potential shortcomings of the new blockbuster model and improve their chances of becoming the successful players of tomorrow

The year 2013 is off to a great start in terms of biotechnology and healthcare sector. In my opinion, we will see many volatility due to newer mandates. "The industry has done a lot to try and improve productivity and has corrected a lot of past mistakes," Deutsche Bank analyst Richard Parkes tells Reuters. "It's too early to say whether this is going to be a sustained break-out from the trend but the efforts that have been put in place should at least improve the efficiency of what is being spent."

Reuters' two top analysts, Ben Hirschler and Bill Berkrot, have scanned the horizons and identified a slate of the top potential blockbusters now in Phase III.

Multiple Sclerosis:

Biogen Idec's ($BIIB) MS drug BG-12 is expected to win FDA approval and go on to take up larger market share with best-in-class potential.

Diabetes:

Johnson & Johnson ($JNJ) is also tackling Endocrinology space with the SGLT2 diabetes drug canagliflozin, given a thumbs up at a recent advisory panel meeting with a good shot at penetrating a $7 billion market.
Also in line, Novo Nordisk's ($NVO) long-acting insulin Tresiba and separate blockbuster effort to get liraglutide for obesity.

Hepatitis C:

With a HepC bubble in mid-late 2012, Gilead ($GILD) and AbbVie ($ABBV) are also in race for a new hepatitis C drug that can quickly emerge as the new standard of treatment.

Cancer:

Roche ($RHHBY) has T-DM1 in Phase 3 which is a potent microtubule polymerization inhibitor conjugated to trastuzumab.

Others:

Lilly ($LLY) has 13 drugs in Phase III.
GSK ($GSK) now has 6 drugs up for regulatory approval.

I am mostly interested in the small cap biotechnology companies but I felt this article will provide a global picture on biotechnology sector.

Disclosure: No position in any of the companies mentioned above

Sources: FierceBiotech, Reuters, Google Finance

New Drug on horizon: Tedizolid by Trius Therapeutics

2012-12-27T14:00:00.000-05:00

-Shruti Desai, PharmD Candidate
Trius Therapeutics (NASDAQ: TSRX) is a biopharmaceutical company focused on the developing innovative antibiotics for life-threatening infections. The current drug named Tedizolid phosphate is in its late clinical stage.

Tedizolid phosphate is a 2nd generation oxazolidinone being developed for the treatment of serious gram-positive infections, including those caused by MRSA. There is also a strong growth of MRSA treatment days. In the day and age of cost-containment, the lower number of hospital days is highly preferred.

Tedizolid phosphate is a novel prodrug that is cleaved in the blood stream to the active compound from Tedizolid phosphate to Tedizolid. As a second generation oxazolidinone, tedizolid phosphate is chemically different from, and designed for improved potency, resistance and spectrum of activity over, the first generation oxazolidinones such as linezolid (Zyvox). There is only one approved first generation oxazolidinone, linezolid, which is currently the leading branded antibiotic for serious gram-positive infections, with reported worldwide sales of $1.3 billion in 2011.

A recent journal article has clearly demonstrated that there is an active emergence of linezolid-resistance Staphylococcus aureus. Linezolid remains active against >98% of Staphylococcus, with resistance identified in 0.05% of Staphylococcus aureus and 1.4% of coagulase-negative Staphylococcus (CoNS). The emergence of linezolid resistance in Staphylococcus poses significant challenges to the clinical treatment of infections caused by these organisms, and in particular CoNS (Gu B. J Antimicrob Chemother. 2012).

Tedizolid can be given IV or orally for the treatment of serious gram-positive bacterial infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). Tedizolid phosphate has successfully completed a Phase 3 trial in patients with acute bacterial skin and skin structure infections (ABSSSI).

Acute bacterial skin and skin structure infections (ABSSI) infections involve deeper tissue or require surgical intervention or are associated with a significant underlying disease (e.g., diabetes or systemic immunosuppression) that complicates response to therapy. A variety of pathogens may be identified in ABSSSI but the two most common Gram-positive pathogens are Staphylococcus aureus and Streptococcus pyogenes. The significant increase in the incidence of MRSA in community as well as hospital acquired infections has resulted in a need for therapy of ABSSSI that is effective against MRSA.

Tedizolid phosphate offers a number of important potential advantages over linezolid, including greater potency, once daily dosing, predictable drug exposure, a shorter course of therapy, in vivo bactericidal (i.e., bacterial killing) activity, lower frequency of resistance, activity against linezolid-resistant bacterial strains and an improved safety profile. TSRX is planning to develop this drug to treat multiple clinical indications, such as infections of the lung and blood, such as, hospital acquired pneumonia (HAP), ventilator acquired pneumonia (VAP) and bacteremia.

Some Advantages of Tedizolid

Greater Potency

Shorter Dosing Regimen and Once Daily Dosing.
Tedizolid Phosphate is administered once daily for six days for the treatment of cSSSI (now termed ABSSSI), as compared to twice daily for 10 to 14 days for linezolid. This tremendously help with patient convenience

Activity against Key Gram-Positive Drug-Resistant Strains and Select Atypical and Gram-Negative Bacteria.

Tedizolid phosphate is also active against gram-negative bacterium Legionella and strains of the atypical bacterium Chlamydia, and thus may have utility in treating lower respiratory tract infections involving these bacteria.

Favorable and Predictable Pharmacokinetics

There is little patient-to-patient variability in the concentration of tedizolid phosphate in blood, as compared to linezolid. As a result, we expect that tedizolid phosphate will have more predictable drug exposure which may lead to a more uniform efficacy and safety profile across different patients when compared to linezolid.

Fewer Drug-Drug Interactions

Unlike linezolid, tedizolid phosphate has not been shown to inhibit the monoamine oxidase system which mediates the metabolism of tyramine, SSRI's and vasoconstrictors.

Tedizolid phosphate may provide MDs with a safe antibiotic for the treatment of serious gram-positive infections that is more potent and more convenient than linezolid and other currently available alternatives.

1st Pivotal Phase 3 trial (ESTABLISH-1):

Trius has announced positive top-line results from our first Phase 3 clinical trial in acute bacterial skin and skin structure infections, or ABSSSI. The study was looking at Tedizolid vs. Linezolid for the Treatment of Acute Bacterial Skin and Skin Structure Infections. (ABSSSI). This was a randomized, double-blind, double dummy, multicenter Phase 3 study of oral Tedizolid 200 mg once daily for 6 days versus oral Zyvox (linezolid) 600 mg every 12 hours for 10 days for the treatment of ABSSSI in adults.

Primary objective: To determine the noninferiority in the early clinical response rate (see the image below)

Patients with systemic signs of infection diagnosed with acute bacterial skin and skin structure infection (ABSSSI) and patient diagnosed with Cellulitis/ erysipelas, major cutaneous abscess, or wound infections were included in the study. Patients with uncomplicated skin infections, severe sepsis or septic shock and ABSSSI solely due to gram-negative pathogens were excluded to clearly assess the primary endpoint.

Results:

In the Intent to Treat (ITT) analysis set, tedizolid achieved the primary objective of non-inferiority (10% non-inferiority margin) to linezolid in the primary and secondary efficacy endpoints. The primary endpoint was cessation of lesion spread and resolustion of fever at 48-72hours after initiation of study drug.

Top-Line Data from the TR701-112 Trial

CE = Clinically Evaluable

Both tedizolid and linezolid were generally well tolerated with comparable overall safety profiles, with drug-related treatment emergent adverse events (TEAE) reported in 24.2% of tedizolid patients versus 31.0% of linezolid treated patients.

*Statistically Significant (p=0.004).

In terms of adverse events, they were higher in linezolid group (31.0%) vs tedizolid (24.2%). Tedizolid showed improved GI tolerability and nausea, vomiting, and diarrhea were statistically significantly in favor of tedizolid (16.3%vs 24.4%, p<0.05)

Tedizolid also had less of a detrimental effect on platelet count (-9.2% for tedizolid vs. -14.9% for linezolid), including percent consider abnormally low (<75% LLN) at 2.3% for tedizolid vs. 4.9% for linezolid.

The data suggest that tedizolid also had less of a detrimental effect liver function. ALT above the normal limit was 27.7% for tedizolid at EOT versus 33.0% for linezolid.

The data from this trial was presented at 52nd Annual Interscience Conference on Antimicrobial agents and Chemotherapy (ICAAC) in September 2012.

2nd Phase 3 trial (ESTABLISH-2)

TSRX is currently running a 2nd Phase 3 trial which expects to report top-line data in early 2013. This is also a randomized, double-blind, double-dummy, multicenter, global Phase 3 study of IV to oral TR-701 FA 200 mg once daily for 6 days versus IV to oral Zyvox® (linezolid) 600 mg every 12 hours for 10 days for the treatment of ABSSSI in adults. Patients are to start treatment with at least 2 IV doses and may receive IV therapy for the entire treatment duration. The 113 study is the first clinical trial conducted in collaboration with Bayer HealthCare and will recruit patients in North and South America, Europe, Australia, New Zealand, and South Africa.

The primary endpoint for the 2nd phase 3 pivotal trial is to determine the noninferiority (NI) in the early clinical response rate of intravenous (IV) to oral 6 day TR-701 free acid (FA) compared with that of IV to oral 10-day linezolid treatment at 48-72 hours after the first infusion of study drug in the intent-to-treat (ITT) analysis set in patients with acute bacterial skin and skin structure infections (ABSSSI).

In this trial, patients requiring IV antibiotic therapy and with systemic signs of infection diagnosed with ABSSSI and diagnosed with Cellulitis/ erysipelas, major cutaneous abscess, or wound infections were included. Patients with uncomplicated skin infections, severe sepsis or septic shock and ABSSSI solely due to gram-negative pathogens were excluded. As you can the inclusion and exclusion criteria are similar to 1st pivotal phase 3 trial. With this in mind it the chances of this trial being successful are very high.

Trius reported 3rd quarter which ended on September 30, 2012, with approximately $70.9 million in cash and investments. During the first nine months of the year, Trius burned approximately $46.7 million in cash from operating and investing activities. At the same time, TSRX has offset this by raising proceeds totaling $48.9 million through financing activities. On August 31, 2012, the company participated in a common stock purchase agreement (CSPA) with Terrapin Opportunity, L.P. to sell Terrapin up to $25 million in registered shares of common stock over a 24-month period. On January 17, 2013, TSRX announced a public offering of 6.3M shares of its common stock $4.75 per share. The gross proceeds to Trius from this offering are expected to be approximately $29,925,000 million. The offering is expected to close on or about January 24, 2013. Certainly, no one likes dilution but TSRX is being conservative and keeping enough cash on hand for its potential NDA submission and other clinical development program.

I strongly believe that commercial success for tedizolid in the U.S. to have peak sales in the $350M - $400M range (with positive ESTABLISH-2 results). The current market share is dominated by vancomycin, linezolid and off-label daptomycin. In US the combined market share of linezolid, daptomycin, cefteroline, and vancomycin is estimated to be $2 billion. Use of Cubicin and Zyvox is up 40%-50% over the past 12 months versus a near 50% decrease in use for generic vancomycin. Now there are many concerns about Vancomycin resistant S. auerus (VRSA). If TSRX is able to get the indications into pneumonia and bacteremia, it would provide tremendous success to the company.

TSRX has already a commercialization deal with Bayer in Asia market. This deal would give TSRX $25million upfront with 25% of the development cost and another $69million in development milestones. In US, they may plan to launch the drug themselves and license to a major pharmaceutical company in Europe which would also bring in additional licensing revenues. The news about Europe market will certainly lift the stock prices. While the price of TSRX may not show any strength since the results are expected in 2013 but this allows for a great opportunity for a strong run up into the 2nd PhaseIII results.

With all that said, TSRX has a great potential to run up to $6 range as we near February before ESTABLISH-2 data.

Price Target: $7

Disclosure: Long TSRX

Resources: Trius Therapeutics Investor Presentation and Corporate presentations, PubMed, Bloomberg, MicroMedex drug database, Clinicaltrial.gov

Is the pullback in Biotechnology sector an opportunity?

2012-10-25T09:30:00.000-04:00

Written by: Ankit Desai (@ankitdesai6)

The year 2012 has been great for the Biotechnology sector. The NASDAQ Biotech Index (NBI) has advanced 31.0% since the beginning of the year, clearly outperforming the broader S&P 500, which has so far gained 12%. In year 2012, large and small biotech companies have launched a number of novel new products and released promising clinical data for drugs in late stage clinical pipeline. After the impressive 31% gain on the index, a healthy pullback in my opinion is warranted. After spending more than 5 years in stock market and 3+ years in biotechnology sector, I have seen that a healthy pullback after stellar upside is very healthy.

In month of October 2012, we have seen a tremendous pullback in small cap biotechnology stocks with pending regulatory catalysts. Several small-cap biotechnology/pharmaceutical companies that I follow or have invested in have seen -10% to -20% declines in month of October 2012. Not only biotechs, Apple Inc. lost 8 percent from the start of the quarter; Google Inc. fell nearly 10 percent; and upscale fast food restaurant Chipotle Mexican Grill fell 25.6 percent to a 20-month low

Will this be an opportunity for traders or small term investor to take a position into their pending regulatory catalyst? I believe so.

Zogenix ($ZGNX)

Possible FDA Advisory Meeting in December 2012
PDUFA on March 1, 2013

Alexza Pharmaceutical,

PDUFA date on December 21, 2012

Vanda Pharmaceutical

Two Phase 3 trial results to be announced in 1^st Q of 2013
Reply to CHMP in October 2012 and expected European approval November 2012

Dynavax Technologies

The FDA advisory panel on November 15, 2012
PDUFA date on February 24, 2013 under standard 10-month review

EXACT Science Corporations

Pivotal study expected late Q4 of 2012

With a healthy pullback in month of October 2012, I will be looking to add position or add more to the existing position in the companies mentioned above.

Disclosure: Long ZGNX, VNDA. May initiate long position in $ALXA, $DVAX, $EXAS in next 72hours

Resources: Reuters, Bloomberg, FDA, Google Finance Charts

Analysis of Catalyst Pharmaceutical (NASDAQ:CPRX)'s Vigabatrin (CPP-109) Pivotal trial sucess

2012-09-28T12:58:00.000-04:00

Written by: Ankit Desai (Twitter: @ankitdesai6)

Catalyst Pharmaceutical Partners (NASDAQ: CPRX) is a specialty biopharmaceutical company focused on the development of drugs targeting diseases and disorders of the central nervous system (CNS), with a focus on the treatment of addiction, infantile spasms, epilepsy and other CNS indications.

Catalyst is developing vigabatrin (CPP-109) for the treatment of addiction to cocaine, methamphetamine and other addictive substances. Catalyst is also developing a more potent vigabatrin analogue (designated CPP-115 by Catalyst) for the treatment of cocaine addiction, infantile spasms and epilepsy, as well as other addiction and CNS indications.

CPP-109 or Vigabatrin

Vigabantrin is an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the metabolism of the inhibitory neurotransmitter GABA. This action results in increased levels of GABA in the central nervous system. This increase in amount of GABA typically has relaxing, anti-anxiety, and anti-convulsive effects. By giving this drug to a cocaine-addict or methamphetamine addict, it prevents them from having withdrawal symptoms and eventually allows them to become free from drug addiction.

Vigabatrin is currently being marketed as Sabril by Lundbeck Pharmaceutical in the US, Canada and EU. Sabril is indicated as adjunctive therapy for adult patients with refractory complex partial seizures (CPS) who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss. I understand the Sabril has a black box warning for irreversible vision loss. You have to keep in mind the risk vs benefit when we are talking about drug addiction patients. The vision loss may be from the dose accumulation which there is not a lot of conclusive results. This will be the focus when they are running a Phase III trial in large population. Since now we are only focusing on Phase IIb trial, I feel this will not be a major hurdle in stock price appreciation.

Catalyst Pharmaceutical is trying to get an initial indication for treating cocaine addiction with expanded indication for methamphetamine later. The patent for CPP-109 is protected until 2018 via “method of use” patent. But, the Waxman Hatch provisions would likely extend protection for five years following its introduction, which might extend protection to 2019 or 2020

Market Potential

According to the National Institute on Drug Abuse Illicit drug use in America has been increasing. In 2010, an estimated 22.6 million Americans aged 12 or older—or 8.9 percent of the population—had used an illicit drug or abused a psychotherapeutic medication. This is up from 8.3 percent in 2002. The increase mostly reflects a recent rise in the use of marijuana, psychotherapeutics and cocaine. The treatment for substance abuse in the United States is likely to increase by 2.5x in the aging population by the year 2020.

Currently, there is a FDA approved medication for opioid addiction called Suboxone (buprenorphine/suboxone) which has annual sales of more than $1B. By doing a simple inference calculation assuming that there will be 1.36M cocaine abuse in coming years will give you an estimate of $600M potential revenue for CPP-109. Since there is not cocaine addiction drug in market, this will prove a tremendous advantage to Catalyst Pharmaceutical

Clinical Trials

CPRX has completed a Phase II trial (not pivotal trial) that was published in American Journal of Psychiatry in 2009 in which primary endpoint (abstinence during last 3 weeks of treatment phase) was met with p value <0.05.

Limitations of this Phase II clinical trial were: study was done in Mexico; the patients were required to visit the treatment center twice a week to give urine and at that time were given their daily dose under observation. For the other five days of the week, they self-administered the drug. See below for the summary of this trial.

These Mexican studies led to a phase II trial in the US (2006-2009) which was similar in design to the phase II Mexican trial. This trial failed to produce a positive topline result which was mainly due to trial design rather than lack of activity of the drug.

The primary endpoint was being abstinent in weeks 11 and 12 of the 12 week study. This was determined by patient self-reporting and also measuring levels of benzoylecgonine, the major metabolite of cocaine, in urine samples. Treatment adherence was evaluated through pill counts and patient self-reporting.

The study failed to meet its primary endpoint. In a post hoc analysis which looked at urine samples, it was found that 48% of the 61 CPP-109 patients that stayed in the trial were not compliant with their medication. This lack of compliance had a profound negative influence on the trial outcome. The main reason why I think the study failed is because Mexican trial included patient who were prisoners and were required to follow-up with the clinician twice a week. In the US trial, patients were recruited by academic medical centers through radio and TV ads and who were paid for their participation. In addition, US patients were generally unobserved taking their medicine and were less motivated overall to take their medication.

CPP-109 Phase IIb Pivotal Trial

Catalyst Pharmaceutical is now conducting the pivotal phase IIb trial of CPP-109 in which 200 patients will be enrolled. This time the trial is only enrolling truly motivated patients who have a strong incentive to quit. In this trial, patients will receive no payment for participating in the trial. The endpoint of the study is abstinence at 8-9 weeks with patients then being followed through 24 weeks in total.

In addition, this trial is also co-sponsored by National Institute of Drug Abuse (NIDA) and Department of Veteran Affairs. The company had a PR on July 12, 2012 “Catalyst Pharmaceutical Partners, Inc. (Nasdaq:CPRX) today announced that it expects to report top-line results from its CPP-109 (vigabatrin) Phase II(b) trial around the end of September 2012 versus the previous guidance of early in the first quarter of 2013.”

On September 26, 2012 Catalyst Pharmaceutical announced that it has been advised by the Department of Veterans Affairs Cooperative Studies Program (VACSP) (also a co-sponsorer) that the availability of top-line results from Catalyst's CPP-109 (vigabatrin) Phase II(b) trial for cocaine addiction to be delayed until November 2012. VACSP now expects to provide the top-line results to the Company during the first half of November 2012.

With this press release, the stock price which closed at $1.81 on 09/25 opened at $1.44 (~15% down from its close). After carefully looking at their financials and the pivotal clinical trial design, I think the selling is overdone here. On August 28, 2012 Catalyst Pharmaceutical already raised $6M in registered direct offering for each share at $1.50. This $1.50 price makes a really good support for this company in short term. In addition, CPRX also released a PR on August 30th announcing the closing of $6M registered direct offering. As you can see, the risk of dilution is very very low. Since we are only 1.5 months away from its top-line pivotal trial results, I believe we will see a potential upside to the stock to at least $1.90-2.00.

The company has market cap of approximately $51M. Since this is a low float company, the hedge fund managers and traders can manipulate it very easily. The company currently has $13.0M in cash so the risk for offering and/or dilution is not there.

In my personal opinion, the company will see an appreciation in price once we are middle of October which will give it an exact 1 month period. I am planning on taking a Long position in this company at $1.35-$1.40 area if it goes there.

Price Target: $2.00 (This is a very conservative price target)

Once again, before you invest please read the disclaimer. This is analysis is my own opinion.

Disclosure: Long $CPRX

References:

National Institute of Health. National Institute on Drug Abuse (NIDA). Drug Facts: Nationwide Trends. August 2012. http://www.drugabuse.gov/publications/drugfacts/nationwide-trends

Catalyst Pharmaceutical Partners – Investor Relations

Sabril (Vigabatrin) Product Package Insert. http://www.lundbeck.com/upload/us/files/pdf/Products/Sabril_PI-CPS_US_EN.pdf

Google Finance

Bloomberg

Reuters

New Drug on horizon: Zogenix (NASDAQ: ZGNX)'s Zohydro ER (extended release Hydrocodone bitartrate)

2012-09-21T11:47:00.001-04:00

Written by: Ankit Desai (@ankitdesai6)

Zogenix, Inc. (NASDAQ: ZGNX) is a pharmaceutical company commercializing and developing products for the treatment of central nervous system disorders and pain. Zogenix’s lead product candidate, Zohydro (hydrocodone bitartrate, formerly ZX002) is a 12-hour extended-release formulation of hydrocodone without acetaminophen for the treatment of chronic pain requiring opioid therapy. It has completed its pivotal phase 3 clinical trials in 2011 and submitted its NDA with PDUFA date in March 2012. $ZGNX also has approved Sumavel DosePro product which offers needle-free subcutaneous administration of sumatriptan for the treatment of migraine and cluster headache in a pre-filled, single-use delivery system. ZGNX is also developing its second DosePro investigational product candidate, Relday, which is an injectable formulation of risperidone for the treatment of schizophrenia.

Zohydro ER (Hydrocodone bitartrate ER)

Zohydro ER is an oral agent without acetaminophen and extended-release formulation of various strengths of hydrocodone dosed every 12 hours for around-the-clock management of moderate-to-severe chronic pain. Zohydro ER could be the first hydrocodone product to offer the benefit of less frequent dosing and the ability to treat chronic pain patients without the risk of liver injury associated with the use of acetaminophen in high dosages or over long periods of time.

image: suuplements-daily.com

Chronic pain is ongoing or recurrent pain that adversely affects an individual's wellbeing. An estimated 116 million people in the United States are burdened with chronic pain, at a national economic cost of $560 to $635 billion annually. Currently, hydrocodone is only available in immediate-release, combination products, most commonly with the analgesic acetaminophen, and requires dosing every 4 to 6 hours. There is an established need for a single-entity (non-acetaminophen) hydrocodone medicine to provide people suffering from moderate-to-severe chronic pain with an effective option to manage their pain without the significant risk of liver injury associated with the use of acetaminophen in high dosages or over long periods of time. Research has shown that approximately 30-35% of hydrocodone combination products are taken on a chronic basis, for which there is ample evidence that this presents a health risk.

In 2012, there was a large study that was published by the University of Cincinnati Drug and Poison Information center that looked at the trends in hepatic injury associated with unintentional overdose of acetaminophen in products with and without opioids. There were total of 119,731 cases that were identified in which patient used acetaminophen with opioid containing product. The incidence of cases increased 70% from year 2000 to 2007. In this study, acetylcycteine treatment was used to treat hepatic injury caused by acetaminophen. Recommendations for acetylcysteine rose 252%, minor injuries rose 833%, severe injuries rose 280% and both together rose 500% (all trends p<0.01). This tells you that the hepatic injury is a serious issue when acetaminophen is used in excess. In this study, acetaminophen with opioid-related hepatic injuries rose much faster than acetominophen without opioid-related injuries (500% versus 134% over year 2000-2007). Injuries rose even though an increasing percentage of patients are being treated with acetylcysteine.

This study supports the FDA panel's recommendation to remove acetaminophen from opioid products but not to remove acetaminophen from non-prescription combination cough and cold products. While it has always been true that removing acetominophen from opioid combination products would eliminate these products as a source of acetominophen-related injury, this study provides additional motivation, demonstrating that these products represent a significant and growing portion of those unintentionally injured from overuse of acetaminophen. As you can see, FDA has a strong support for removal of acetaminophen from the opioid products. Currently, there are many opioids products that are in the market and personally I see 30-40% of Rx at the pharmacy being acetaminophen containing opioid products.

Hydrocodone is the only opioid not currently available in ER form and available only in combination with APAP/NSAID; FDA advisory committee noted single entity formulation of hydrocodone would be logical substitute. FDA has recently asked manufacturers to limit acetaminophen to 325 mg in combination products and will require updated labeling information warning about the risk of severe liver injury

ZGNX completed its pivotal Phase III trial in October 2011. Below is the summary of the study design and the results:

Title: Phase 3 Study of Hydrocodone Bitartrate Controlled-release Capsules in Subjects With Chronic Low Back Pain

A randomized Phase 3, placebo-controlled multi-center study to evaluate the safety, efficacy and tolerability of Hydrocodone Bitartrate controlled-release capsules in subjects with chronic low back pain. Subjects will go through an open-label conversion and titration phase followed by a randomized double-blind treatment phase of HC-CR vs. Placebo. The trial will consist of a Screening Phase (up to 14 days), an open-label Conversion and Titration Phase (up to 6 weeks), a 12-week placebo-controlled Treatment Phase, and a 2-week Follow-Up Phone Call.

Inclusion Criteria:

Subjects must have a clinical diagnosis of moderate to severe CLBP
Subjects must be classified as non-neuropathic, neuropathic, or symptomatic for more than 6 months after LBP surgery
Subjects must in the Investigator's opinion qualify for around-the-clock opioid therapy for treatment of their CLBP.
Subjects must have been taking opioids for at least 5 days/week for the past 4weeks
Subjects must have an average Clinic Pain Score of ≥ 4 on the 11-point (0-10) NRS as an average for the last 24 hours of Screening
Subjects, in the opinion of the Investigator, must be considered to be in generally good health other then CLBP at Screening
Female subjects of childbearing potential must have a negative urine pregnancy test at the Screening Visit, and must consent to use a medically-acceptable method of contraception throughout the entire study period.
Subjects must voluntarily provide written informed consent.

Exclusion Criteria:

Any clinically significant condition that would, in the opinion of the Investigator, preclude study participation or interfere with the assessment of pain and other symptoms of CLBP or increase the risk of opioid-related adverse events
A medical condition that, in the opinion of the Investigator, would compromise the subject's ability to swallow, absorb, metabolize, or excrete the study drug
A surgical procedure for back pain within 6 months
A nerve or plexus block, including epidural steroid injections or facet blocks
A history of chemotherapy or confirmed malignancy within past 2 years
Any other chronic pain condition other than CLBP that, in the Investigator's opinion, would interfere with the assessment of LBP e.g. fibromyalgia, osteoarthritis, rheumatoid arthritis, migraine headaches requiring opioid treatment
Uncontrolled blood pressure, i.e., subject has a sitting systolic blood pressure >180 mmHg or <90 mmHg, and/or a sitting diastolic blood pressure >120 mmHg or <50 mmHg at Screening
A Body Mass Index (BMI) >45 kg/m2
A Hospital Anxiety and Depression Scale (HADS) Index score of >12 in either depression or anxiety subscales or an established history of major depressive disorder that is poorly controlled with medication
A clinically significant abnormality in clinical chemistry, hematology or urinalysis

Location: only United States

Results:

The pivotal phase 3 successfully met its primary efficacy endpoint, demonstrating that Zohydro ER resulted in significantly (p=0.008) improved chronic pain relief compared to placebo. The two key secondary endpoints in this study - the proportion of patients with at least 30% improvement in pain intensity and the improvement of overall satisfaction of medication - were also met.

Additional study endpoints were supportive of the efficacy of Zohydro ER compared to placebo. Overall, the most commonly reported adverse events (≥2%) in the placebo-controlled pivotal Phase 3 efficacy Study 801 in opioid-experienced patients were consistent with those typically seen with chronic opioid therapy and were constipation, nausea, somnolence, fatigue, headache, dizziness, dry mouth, vomiting and pruritus. Study 802, in which patients received Zohydro ER for up to 12 months, further investigated Zohydro ER's tolerability and safety profile and showed that the incidence of adverse events was consistent with that seen in the pivotal Phase 3 efficacy study.

The PDUFA for Zohydro is in March 01, 2013 with potential FDA advisory panel meeting (http://www.fda.gov/AdvisoryCommittees/Calendar/ucm153468.htm). With these two strong catalyst, there is a strong possibility of $ZGNX stock to make a run in anticipation of FDA results and AdCom decision.

Financial Standings

Zogenix currently has $22M in cash as of 06/30/2012 which excludes the net proceeds of $65.5M from July 2012 equity offering and $21.2M repayment of term loan debt obligations to Oxford and Silicon Valley bank. In my opinion, the company has enough cash position into the PDUFA date. Since they recently completed equity offering of ~$65M, the possibility of another dilution is very little. Once again, with the small cap Biotechnology Company there is always a risk of additional dilution and/or ATM. With these two strong upcoming catalysts we will see a dramatic appreciation in stock price as we get near AdCom meeting in December 2012.

Price target: $4.00

Disclosure: No position, may initiate a position in next 72hours

Reference:

Zogenix Corporate Presentation
Bond GR et al. Drug Saf. 2012. Feb 1; 35 (2): 149-57
Chronic Pain. American Chronic Pain Association. Accessed 12 April 2012.
Available at: http://theacpa.org/conditionDetail.aspx?id=74
Institute of Medicine Report from the Committee on Advancing Pain Research, Care, and Education: Relieving Pain in America, A Blueprint for Transforming Prevention, Care, Education and Research. The National Academies Press, 2011.Accessed 12 April 2012. http://books.nap.edu/openbook.php?record_id=13172&page=1
Farrell, SE. Acetaminophen Toxicity. Medscape. 6 February 2012. Accessed 12 April 2012.
Available at: http://emedicine.medscape.com/article/820200-overview
Micromedex. Thompson Reuters. 2012
Reuters, Yahoo Finance

Excellent mid-term investment opportunity: Trius Therapeutics (NASDAQ:TSRX) and its late stage lead drug Tedizolid

2012-09-17T11:08:00.004-04:00

Written by: Ankit Desai (twitter:@ankitdesai6)
Trius Therapeutics (NASDAQ: TSRX) is a biopharmaceutical company focused on the developing innovative antibiotics for life-threatening infections. The current drug named Tedizolid phosphate is in its late clinical stage.

Tedizolid phosphate is a 2^nd generation oxazolidinone being developed for the treatment of serious gram-positive infections, including those caused by MRSA. There is also a strong growth of MRSA treatment days. In the day and age of cost-containment, the lower number of hospital days is highly preferred.

Tedizolid can be given IV or orally for the treatment of serious gram-positive bacterial infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). Tedizolid phosphate has successfully completed a Phase 3 trial in patients with acute bacterial skin and skin structure infections (ABSSSI).

VisualDx - ABSSI

Acute bacterial skin and skin structure infections (ABSSI) infections involve deeper tissue or require surgical intervention or are associated with a significant underlying disease (e.g., diabetes or systemic immunosuppression) that complicates response to therapy. A variety of pathogens may be identified in ABSSSI but the two most common Gram-positive pathogens are Staphylococcus aureus and Streptococcus pyogenes. The significant increase in the incidence of MRSA in community as well as hospital acquired infections has resulted in a need for therapy of ABSSSI that is effective against MRSA.

Greater potency

Shorter dosing regimen and once daily dosing

· Tedizolid Phosphate is administered once daily for six days for the treatment of cSSSI (now termed ABSSSI), as compared to twice daily for 10 to 14 days for linezolid. This tremendously help with patient convenience·

· Activity against gram-positive drug-resistant strains and select atypical and gram-negative bacteria

· Tedizolid phosphate is also active against gram-negative bacterium Legionella and strains of the atypical bacterium Chlamydia, and thus may have utility in treating lower respiratory tract infections involving these bacteria.

· Favorable and predictable pharmacokinetics

· There is little patient-to-patient variability in the concentration of tedizolid phosphate in blood, as compared to linezolid. As a result, we expect that tedizolid phosphate will have more predictable drug exposure which may lead to a more uniform efficacy and safety profile across different patients when compared to linezolid.

· Fewer drug-drug interactions

· Unlike linezolid, tedizolid phosphate has not been shown to inhibit the monoamine oxidase system which mediates the metabolism of tyramine, SSRI's and vasoconstrictors.

1st Pivotal Phase 3 trial (ESTABLISH-1):

Trius has announced positive top-line results from our first Phase 3 clinical trial in acute bacterial skin and skin structure infections, or ABSSSI. The study was looking at Tedizolid vs. Linezolid for the Treatment of Acute Bacterial Skin and Skin Structure Infections. (ABSSSI). This was a randomized, double-blind, double dummy, multicenter Phase 3 study of oral Tedizolid 200 mg once daily for 6 days versus oral Zyvox (linezolid) 600 mg every 12 hours for 10 days for the treatment of ABSSSI in adults.

Primary objective: To determine the noninferiority in the early clinical response rate (see the image below)

Results:

In the Intent to Treat (ITT) analysis set, tedizolid achieved the primary objective of non-inferiority (10% non-inferiority margin) to linezolid in the primary and secondary efficacy endpoints.

TSRX is currently running a 2nd Phase 3 trial which expects to report top-line data in early 2013.

This is also a randomized, double-blind, double-dummy, multicenter, global Phase 3 study of IV to oral TR-701 FA 200 mg once daily for 6 days versus IV to oral Zyvox® (linezolid) 600 mg every 12 hours for 10 days for the treatment of ABSSSI in adults. Patients are to start treatment with at least 2 IV doses and may receive IV therapy for the entire treatment duration. The 113 study is the first clinical trial conducted in collaboration with Bayer HealthCare and will recruit patients in North and South America, Europe, Australia, New Zealand, and South Africa.

The primary endpoint for the 2nd phase 3 pivotal trial is to determine the noninferiority (NI) in the early clinical response rate of intravenous (IV) to oral 6 day TR-701 free acid (FA) compared with that of IV to oral 10-day linezolid treatment at 48-72 hours after the first infusion of study drug in the intent-to-treat (ITT) analysis set in patients with acute bacterial skin and skin structure infections (ABSSSI).

In this trial, patients requiring IV antibiotic therapy and with systemic signs of infection diagnosed with ABSSSI and diagnosed with Cellulitis/ erysipelas, major cutaneous abscess, or wound infections were included. Patients with uncomplicated skin infections, severe sepsis or septic shock and ABSSSI solely due to gram-negative pathogens were excluded. As you can see the inclusion and exclusion criteria are similar to 1st pivotal phase 3 trial. With this in mind it the chances of this trial being successful are very high.

On August 6, 2012, $TSRX reported that they have $84M in cash and R&D expense for the three month (April, May and June) was $16.4M so when we extrapolate that or multiply that by 4 it gives us a rough estimation of their burn rate compared to their net cash that they have. $16M x 4 = $64M. Since they have enough cash on their hand going into the top-line Phase 3 trial results, I believe the possibility of offering is low. The share price has gone up 8%-10% in month of September 2012. They recently reported data on Broad-spectrum Antibiotic at 52nd Annual ICAAC Meeting. With the release of the abstracts and various presentations at academic centers and financial firms, TSRX is creating a lot of buzz in the investor community, medical community as well as retail investors. The upcoming Phase 3 (ESTABLISH-2) trial will certainly add on to the anticipation and excitement to the company. I also feel strong about the management and their expertise and seeing great potential in TSRX. Once again, I am looking forward to the announcement by TSRX soon about the potential completion PR or more update on their Phase 3 trial result.

Resources: Trius Therapeutics Investor Presentation and Corporate presentations, PubMed, Bloomberg, MicroMedex drug database, Clinicaltrial.gov

Disclosure: May initiate a position in next 72hours

ACADIA Pharmaceutical (NASDAQ:ACAD) Phase III data to be released in November 2012

2012-09-05T18:25:00.000-04:00

ACADIA (NASDAQ: ACAD) announced the completion of enrollment in its ongoing pivotal Phase III trial with pimavanserin in patients with Parkinson’s disease psychosis (PDP). Top-line results from this trial are expected to be announced by the end of November 2012.

http://news.acadia-pharm.com/phoenix.zhtml?c=125180&p=irol-newsArticle&ID=1731607&highlight=

Reasons why I think the Phase III (-020) trial will be successful:

The trial will test only 40mg pimavanserin vs. placebo in a 1:1 randomization compared to 3 arms in the previous phase failed trial. It should help reduce the statistical complexity

This trial also has two-week lead-in period which include social therapy in order to help pull initial placebo responses ahead of the assessment period. This will help rule out placebo effect

The trial has new Scale for the Assessment of Positive Symptoms (SAPS) endpoint through analysis of the two previous trials -012 and -014. The new trial will focus on 9 items compared to 20 items in previous failed trials. The SAPS endpoint was accepted by the FDA

Most importantly, this trial will enroll a more homogeneous patient population (US patient population ONLY). The previous failed trial enrolled patients in seven different countries (U.S., U.K., France, Bulgaria, India, Russia, and Ukraine)

Since now we have a clear timeline of the phase III data release. This poses a great near term opportunity for us to take a stock position. I feel as we get near end of October and early November, we will see good number of press releases about this drug. I can see this stock trading near $2.00 to $2.20 range as we get near the data release and once day trader starts scanning this stock. I also feel the that data will be positive due to very careful modification of clinical trial.

I was surprised to see ACADIA (NASDAQ:ACAD) hold its 1.80 support all day today (September 5th, 2012). Normally, small biotech companies like this tend to sell off after a news release. This can be a positive for this stock. Once again, this drug has a unique mechanism of action and has an unmet need.

Pimvanserin

Pimavanserin is a new chemical entity that can be taken orally as a tablet once-a-day. Pimavanserin selectively blocks the activity of the 5-HT2A receptor, a drug target that plays an important role in psychosis.

Parkinson’s disease psychosis, or PDP, is a debilitating disorder that develops in up to 60 percent of patients with Parkinson’s disease. PDP is characterized by the presence of hallucinations and delusions.

Disclosure: May initiate position in next 72 hours

Resources: Reuters, Acadia Pharmaceutical Investor Relations, Google Images, Journal of Clinical Psychiatry, Abilify Package Insert

NASDAQ: IRWD - Linaclotide wins FDA Approval

2012-08-30T15:19:00.005-04:00

Ironwood Pharmaceuticals Inc. (IRWD) and Forest Laboratories Inc. (FRX) won U.S. regulatory approval of their linaclotide treatment for irritable bowel syndrome with constipation.

The therapy was also approved for chronic constipation, the Food and Drug Administration said in a statement on its website today. As many as 11 million Americans have irritable bowel syndrome with constipation, a disorder that causes abdominal pain, according to Cambridge, Massachusetts-based Ironwood.

Linaclotide will compete with Takeda Pharmaceutical Co. (4502)’s Amitiza, which generated 18.7 billion yen ($237.6 million) for the Japanese drugmaker in the 12 months ended in March. Peak sales for linaclotide may reach $1.35 billion, Edward Nash, an analyst with Cowen & Co., said in an Aug. 28 interview. The drug may help reduce patients’ pain, an important element in the treatment of IBS-C, he said.

“That’s the really big differentiator for the drug,” Nash said by telephone. “At the end of the day, why is a patient going to even come to the doctor? Yes, it’s because they’re constipated or have diarrhea, but it’s the pain associated with that that’s so significant.”

Linaclotide was developed by Ironwood with New York-based Forest Labs, and the companies will co-promote the drug in the U.S. Ironwood licensed the drug in Europe to Barcelona, Spain- based Almirall SA (ALM), and to Tokyo-based Astellas Pharma Inc. (4503) for several Asian countries.

Forest rose 1.2 percent to $35.06 at 11:54 a.m. New York time. Ironwood shares were halted before the news.

Linaclotide was shown in studies to help alleviate abdominal pain and symptoms of constipation. The most common side effect was diarrhea, which might be expected “as a side effect for treating constipation; you’re going to overshoot the mark,” Nash said.

Source: Businessweek

A great near term opportunity - Exelixis (NASDAQ:EXEL) - novel treatment for medullary thyroid cancer

2012-08-13T18:16:00.002-04:00

Exelixis, Inc. (Exelixis) is a biotechnology company engaged in developing small molecule therapies for the treatment of cancer. The Company is focusing its resources and development efforts on cabozantinib (XL184).

Cabozantinib is a potent inhibitor of MET, VEGFR2 and RET. RET is a receptor tyrosine kinase that is frequently activated by point mutation in medullary thyroid carcinomas.

The therapeutic role of cabozantinib is also currently being investigated across several tumor types.

MET Oncogene

MET is a proto-oncogene that encodes hepatocyte growth factor receptor protein. MET is upregulated in many tumor types, thus facilitating tumor cell escape by promoting the formation of more aggressive phenotypes, resulting in metastasis.

MET-driven metastasis may be further stimulated by hypoxic conditions in the tumor environment, which are often exacerbated by selective VEGF-pathway inhibitors.

Simultaneous inhibition of MET and VEGFRs by cabozantinib is desiged to provide broad spectrum anti-tumor acitivity, blockade of a key mechanism of evasinve resistance, and reduced metastatis and improved survival.

In preclinical studies, cabozantinib has shown powerful tumoricidal, antimetastatic and antiangiogenic effects, including:

Extensive apoptosis of malignant cells
Decreased tumor invasiveness and metastasis
Decreased tumor and endothelial cell proliferation
Blockade of metastatic bone lesion progression
Disruption of tumor vasculature

Medullary thyroid carcinoma (MTC)

MTC is a distinct thyroid carcinoma that originates in the parafollicular C cells of the thyroid gland. These C cells produce calcitonin.
Medullary thyroid cancer (MTC) is usually diagnosed on physical examination as a solitary neck nodule, and early spread to regional lymph nodes is common.

In addition to producing calcitonin, MTC cells can produce several other hormones, including corticotropin, serotonin, melanin, and prostaglandins; moreover, paraneoplastic syndromes (eg, carcinoid syndrome, Cushing syndrome) can occur in these patients.
Medullary carcinoma of the thyroid (MTC) is prevalent in approximately 4% of all thyroid cancers in the United States. This figure translates into approximately 1000 diagnoses per year. Various clinical trials have shown promising results and tolerable toxicity. However, these studies are still in the early stages, and these therapies are not yet FDA approved. Surgery remains the standard treatment for medullary thyroid carcinoma (MTC)
Patients with distant metastases have a median survival of ~2 years.
Radiographically progressive MTC is an unmet medical need not previously studied in a phase 3 trial
Hepatocyte growth factor receptor (MET) and vascular endothelial growth factor receptor 2 (VEGFR2) pathways have been implicated in the pathogenesis of MTC.

In June 2012, Exelixis reported data from the phase 3 pivotal trial of cabozantinib in patients with progressive, unresectable, locally advanced or metastatic medullary thyroid cancer (MTC).

Trial design:

Eligibility Criteria:

The trial met its primary endpoint of improving progression-free survival (PFS), with patients in the cabozantinib arm achieving a median PFS of 11.2 months compared with 4.0 months for patients in the placebo arm.

Overall response rate (ORR), a secondary endpoint, was 28% in the cabozantinib arm and 0% in the placebo arm. Estimated PFS at one year was 47.3% with cabozantinib vs. only 7.2% with placebo. Data for overall survival (OS), another secondary endpoint, are not yet mature. Patients on the cabozantinib arm of the trial received a dose of 140 mg (free base equivalent).

Adverse events were generally manageable allowing for treatment with cabozantinib for prolonged periods of time.

On July 30, 2012 the FDA granted priority review for Cabozatinib in Medullary Thyroid Cancer with PDUFA date of November 29, 2012.

On August 06, 2012, Exelixis unveiled plans to offer 20 million shares and $225 million in debt to raise funds for clinical trials and other general corporate purposes. Exelixis, had said on the 6^th that it expected to raise about $105.6 million in net proceeds from the common stock offering, based on an assumed offering price of $5.58 a share.

On August 09, 2012, Exelixis Inc.'s (EXEL) upsized 30 million share offering priced at a 0.7% discount to Wednesday's close. The company said it anticipates its aggregate net proceeds from the concurrent offerings will be $361.9 million after deducting the underwriting discount and estimated offering expenses.

Exelixis has said it could use the proceeds for research and development, capital expenditures and working capital, as well as to fund the escrow account to be used for the first six scheduled semi-annual interest payments.

With this raising off the table and enough cash thru the PDUFA, the stock price is likely to go up 20-30% as we near the November. Since Exelixis has a priority review, the result may come as soon as October 2012. The most recent example was Curis Pharmaceutical (NASDAQ:CRIS). The stock has taken a very bad hit in last week down almost 25%-30%. This may pose a great opportunity for small investor to take a position and get nice return on their investment. In the past, EXEL has been very volatile so keep in mind to not to take a large position now, try to scale in smaller positions and average down.

Disclosure: May initiate a position in next 72hours

Resources: Wall Street Journal, Exelixs Investor Presentation, Reuters, ASCO – Cabozantinib Presentation 2012

A Promising Drug on horizon: Acadia Pharmaceutical (NASDAQ:ACAD) and treatment of Parkinson's disease psychosis

2012-07-30T22:23:00.001-04:00

ACADIA Pharmaceuticals (NASDAQ: ACAD) is a biopharmaceutical company focused on innovative small molecule drugs that address unmet medical needs in neurological and related central nervous system disorders. They are developing pimavanserin, which is in Phase III development as a potential first-in-class treatment for Parkinson's disease psychosis (PDP).

www.chemnet.com

Brief background on Parkinson’s disease Psychosis (PDP)

Parkinson’s disease is a chronic and progressive neurodegenerative disorder that affects about 1 million people in the United States and from 4-6 million people worldwide.

It is the second most common neurological disorder after Alzheimer’s disease.

Parkinson’s disease involves the death of neurons in a region of the brain that controls movement, creating a shortage of an important neurotransmitter known as dopamine, thereby rendering patients unable to direct or control their movements in a normal manner.

Parkinson’s disease is characterized by well known motor symptoms, including rest tremor, bradykinesia, rigidity, and disturbances of balance and posture, as well as by non-motor symptoms, including psychosis, depression, sleep disturbances, compulsive behaviors and dementia. Among these the onset of psychosis is considered a particularly poor prognostic sign.

Current standard of care is to reduce or withdraw dopaminergic therapy. Use of antipsychotics has been drug of choice for management of symptoms but they tend to counteract the anti-parkinson’s therapy making the therapy even worse. The drug currenly used are Clozapine, Seroquel (quetiapine) and Abilify (aripiprazole) but they come with very bad side effects mainly being agranulocytosis (severely low amount of white blood cell important for immune system and fighting infections)

cnsspectrums.com

Current State of Pimavanserin

In late 2009, Pimavanserin failed to show statistically significant result to prove its efficacy in Phase III trial for PDP when compared to placebo. That trial did not meet its primary endpoint but the key secondary endpoint of motoric tolerability and pimavanserin was generally safe and well tolerated in the study.

In July 2010, they started a new Phase III trial with new trial design. The redesigned study will include only patients from North America, and will exclude mildly psychotic patients. The main goal of the ongoing study is to reduce psychotic symptoms in Parkinson's disease patients. The secondary goal is to check tolerability to the drug pimavanserin.

The study will now enhance the main goal, which Hacksell (CEO) said has already been approved by the U.S. Food and Drug Administration. The CEO Uli Hacksell, has repeatedly said , "We believe pimavanserin has an ideal profile to effectively treat PDP without impairing motor function and, therefore, provides the potential for an important advance in therapy for patients suffering from this large unmet medical need."

The Trial design can be viewed here (NCT01174004), “http://clinicaltrials.gov/ct2/show/NCT01174004?term=acadia&rank=3”

Reasons why I think the Phase III (-020) trial will be successful:

The trial will test only 40mg pimavanserin vs. placebo in a 1:1 randomization compared to 3 arms in the previous phase failed trial. It should help reduce the statistical complexity

This trial also has two-week lead-in period which include social therapy in order to help pull initial placebo responses ahead of the assessment period. This will help rule out placebo effect

The trial has new Scale for the Assessment of Positive Symptoms (SAPS) endpoint through analysis of the two previous trials -012 and -014. The new trial will focus on 9 items compared to 20 items in previous failed trials. The SAPS endpoint was accepted by the FDA

Most importantly, this trial will enroll a more homogeneous patient population (US patient population ONLY). The previous failed trial enrolled patients in seven different countries (U.S., U.K., France, Bulgaria, India, Russia, and Ukraine)

In my opinion, the stock prices should start to run as we approach August 31, 2012. According to their last quarterly result webcast they are projecting on clinical trial completion near end of August 31, 2012. The final data will be released 3 months after that so the final data release will be November 2012. Since we have strong timeline of data release, the stock price should go up considerably.

As we get closer to the mid 4Q 2012 we will start to see more news around ACAD. A recent PR was released on Reuters, http://www.reuters.com/finance/stocks/ACAD.O/key-developments/article/2573125. I am predicting more PRs like this will make this stock very volatile.

Disclosure: May initiate position in next 72 hours

Resources: Reuters, Acadia Pharmaceutical Investor Relations, Google Images, Journal of Clinical Psychiatry, Abilify Package Insert

A great Biotech investment opportunity: Amicus Theraputics (NASDAQ: FOLD) - Migalastat HCl for Fabry Disease

2012-07-25T18:08:00.001-04:00

Amicus Therapeutics (NASDAQ: FOLD) is a biopharmaceutical company focused on the discovery, development and commercialization of novel small molecule, orally administered drugs known as pharmacological chaperones, for the treatment of a range of human genetic diseases.

Amicus (NASDAQ: FOLD) is focused on three key strategic priorities:

The Phase 3 development of its lead program, AT1001 (migalastat HCl) for the treatment of Fabry disease;

A Quick overview of Fabry Disease

Fabry disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called α-galactosidase A (α-GAL).

Nature.com

The role of α-GAL within the body is to break down a complex lipid called globotriaosylceramide (GL-3). Reduced or absent levels of α-GAL activity leads to the accumulation of GL-3 in the affected tissues, including the central nervous system, heart, kidneys, and skin.

This accumulation of GL-3 is believed to cause the various symptoms of Fabry disease, including

Pain
Kidney failure
Increased risk of heart attack and stroke.

Most individuals with Fabry disease have missense mutations in the GLA gene. Missense mutations can alter the structure of α-GAL, which results in the accumulation of the enzyme in endoplasmic reticulum (ER).

As a result of the accumulation of α-GAL in the ER, the enzyme is unable to reach the lysosome, the part of the cell where α-GAL does its work of breaking down substrate.

Market opportunity

It is currently estimated that Fabry disease affects approximately 5,000 to 10,000 people worldwide. The market opportunity is endless with number of Fabry patients on treatment projected to grow by 12%.

Fabry disease is an X-linked recessive genetic disorder that affects both men and women.

Amigal (migalastat HCl)

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=47206758

Migalastat HCl bind to destabilized α-galactosidase A enzyme (α-GAL) and thereby restore its intended biological function of degrading globotriaosylceramide (GL-3) substrate in lysosomes.

Amicus completed multiple Phase 2 studies of AT1001 for the treatment of Fabry disease.
In total, 26 male and female subjects were treated for either 12 or 24 weeks.
Twenty-three of the 26 subjects continued to receive treatment in an ongoing Phase 2 Extension Study designed to evaluate the long-term safety and efficacy of AT1001.
Results from the Phase 2 studies of Amigal indicated that there were no drug-related serious adverse events. The most common adverse events were headache, arthralgia and diarrhea.
In subjects identified as responders to AT1001, treatment resulted in increased levels of the target enzyme (α-Gal A), as measured in white blood cells and in the kidney, and reduced levels of the target substrate (GL-3), as measured in renal interstitial capillary cells from kidney biopsies and in urine.
Additional preliminary results from Phase 2 extension study showed that eGFR has remained stable out to 2-3 years for all subjects continuing in the extension study and the average annual rate of change in eGFR in subjects identified as responders to migalastat HCl, excluding hyperfiltrators, was +2.0 mL/min/1.73m2. Additionally, trends of reduced proteinuria continued to be observed in subjects identified as responders to AT1001

Phase 3 design:

Purpose: compare the effect of AT1001 (migalastat hydrochloride) versus placebo on kidney globotriaosylceramide (GL-3).
Study design: double-blind, randomized, placebo-controlled study will be conducted in 60 patients at approximately 40 sites worldwide. The study will consist of two stages and an open-label treatment extension phase
Primary outcome: kidney GL-3 (assessed histologically in kidney biopsy samples)
Secondary outcome: urine GL-3 levels, renal function (assessed by iohexol GFR, eGFR, and 24-hour urine protein) , and safety and tolerability
Estimated Primary completion date: July 2012

For more info: http://clinicaltrial.gov/ct2/show/NCT00925301?term=NCT00925301&rank=1

Results expected in 3Q of 2012. It is also being evaluated in different indication in Study 013 with results expected in 3Q-4Q of 2012.

In terms of fundamentals of this company, they have $108.2M in cash as of March 31, 2012. The company is planning on spending around $37-43M in R&D. I do not believe the company will need additional capital through its Phase 3 data release and/or NDA submission.

From the Phase 2 results, and the design of Phase 3 trial, I believe the data should be positive. Since 65% of the patients from phase 2 remained on the migalastat HCl monotherapy shows a strong efficacy and safety in this patient population. So far from the observation, there is low dropout rate which significantly strengthens the potential for positive data of phase 3 trial. In addition, GlaxoSmithKline invested additional $18.6million equity investment in this company which now brings their ownership to 19.9%. With positive phase 3 result, they may buyout this company due to its smaller size.

In my opinion, this company should do well in near term as it approaches its phase 3 data release. I strongly believe that the share prices should reach $7-9 with positive result but once again we should see more momentum in share price as the company updates on specific date of data release. Once again, this company can possibly be bought out by GlaxoSmithKline on a positive result and its deep pipeline with various candidates.

Price target: $8

Disclosure: Long

Resources: Amicus Theraputics Website, Reuters, Stockcharts, Clinicaltrial.gov, Pubmed Chemical, and nature.com

New Drug on Horizon: Linaclotide for Chronic Constipation and Irritable Bowel Syndrome - Constipation (Ironwood Pharmaceutical: IRWD)

2012-07-19T18:24:00.000-04:00

Ironwood Pharmaceuticals, Inc., (NASDAQ: IRWD) an entrepreneurial pharmaceutical company, discovers, develops, and commercializes human medicines.

Its lead product candidate, linaclotide, is a guanylate cyclase type-C agonist that completed Phase III clinical trials for the treatment of patients with irritable bowel syndrome with constipation (IBS-C) and chronic constipation (CC).

Ironwood Pharmaceuticals (NASDAQ: IRWD) has collaboration and license agreements with Forest Laboratories, Inc. to co-develop and co-market linaclotide in North America; Almirall, S.A to develop and commercialize linaclotide for the treatment of IBS-C, CC, and other lower gastrointestinal conditions; and Astellas Pharma Inc. to develop and commercialize linaclotide for the treatment of IBS-C, CC, and other gastrointestinal conditions in Japan, South Korea, Taiwan, Thailand, the Philippines, and Indonesia.

More about Linaclotide:

Linaclotide is a GC-C agonist in development for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic constipation (CC).

Complications of chronic constipation include haemorrhoids, faecal impaction (shown here on CT scan) and intestinal perforation | Photo: SPL

The clinical efficacy portion of the linaclotide development program is complete and two long-term safety studies are still ongoing.

Across four Phase 3 efficacy trials in patients with IBS-C or CC, linaclotide met all primary and secondary endpoints encompassing abdominal and bowel symptoms.

In these trials, diarrhea was the most commonly reported adverse event and the most commonly reported adverse event that led to study discontinuation. Most occurrences of diarrhea were reported as mild to moderate. More than 3,200 patients have enrolled in one of two ongoing 18-month open label safety studies.

In April 2012, US FDA notified the companies that it will require a three-month extension to complete its review of the data supporting the New Drug Application (NDA) for linaclotide for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic constipation (CC).

An additional analysis of existing data was recently requested by the FDA to further characterize the relative effect of the two doses of linaclotide that were studied in the Phase 3 CC clinical trials.

Since this analysis was submitted to the FDA within three months of the user fee goal date, the date has been extended by three months, in accordance with applicable regulation. No new data have been requested by the agency to complete the review. FDA action is now expected by September 2012. Ironwood and Forest continue to plan for a 2012 launch.

Ironwood is a relatively mid-cap pharmaceutical company with market capital of $1.43B as of July 2012. It currently has revenue of $71.22M with quarterly revenue growth of 29.70% and gross profit of $65.87M. In addition, it has total cash of $157.65millon which equates to about 1.47 cash per share. If the Linaclotide gets an FDA approval, Ironwood Pharmaceutical company will get $85M milestone payment from Forest Laboratories and $20M milestone from Almirall.

In my opinion, they have enough cash to reach their anticipated PDUFA date on September 2012. According to their recent 2^nd quarter highlights, they also have European MAA under review which we should be able to get a decision in the 2^nd half of 2012. They are also planning on gaining more market share by expanding global access to patient by filing CTA (FDA of China) which is also accepted for review.

I believe that management is very confident in launching the product commercially in 2^nd half of 2012. During Digestive Disease Week of 2012 which showcases more than 5,000 abstracts and lectures in Gastrointestinal research, medicine and technology also had positive reviews for the Linaclotide.

Market Need

IBS-C and Chronic constipation (CC) are chronic conditions characterized by frequent and bothersome abdominal and/or constipation symptoms. Patients with IBS-C experience frequent and recurrent abdominal pain and/or discomfort and constipation symptoms, such as infrequent bowel movements, hard/lumpy stools, and straining during defecation.

In 2010, approximately 40 million people in the U.S. suffered from symptoms of IBS-C or CC, of whom an estimated 18 million patients sought medical care. Patients are often treated with fiber and laxatives; however, according to market research, over 70 percent are not satisfied with current treatment options. This large, highly symptomatic, and dissatisfied patient population could benefit from new treatments.

In my opinion, this company should fare well in upcoming months. I definitely see an upside in stock price from this levels. After reading the recently published randomized trial results (http://www.nejm.org/doi/full/10.1056/NEJMoa1010863), I feel more confident in approval of this drug. There is definitely a need for new treatment in IBS-C and CC since current standard of therapy lacks patient satisfaction. After close consideration and research, my price target for this company is $16-17 in upcoming months with relative volatility due to its midcap.

Disclosure: May own shares in this company in next 72hours.

Sources: Ironwood Pharmaceutical, New England Journal of Medicine, Yahoo Finance, Reuters, Google images

GlaxoSmithKline to invest additional $18.6million in the Amicus Theraputics (NASDAQ:FOLD)

2012-07-18T18:24:00.004-04:00

GlaxoSmithKline to invest additional $18.6million equity investment in the Amicus Therapeutics (NASDAQ: FOLD) for its experimental therapy for Fabry disease, bringing GSK’s total ownership stake to 19.9 percent. They invested $60millon in cash in 2010.

Amicus will commercialize the drug (Migalastat HCL), currently in Phase II and III trials, in the U.S. and GSK will handle marketing in the rest of the world.

Fabry disease, estimated to affect 5,000 to 10,000 people worldwide, is caused by an enzyme deficiency and lists various symptoms – including kidney failure and increased risk of heart disorders.

Migalastat HCl is now in two late-stage studies for Fabry disease, with pivotal data expected in the third quarter.

Three Studies underway for NASDAQ: FOLD

Sources: Amiscus Theraputics, Reuters, FierceBiotech

Vivus Pharma (NASDAQ: VVUS) awaits FDA approval for its obesity drug

2012-07-17T17:21:00.000-04:00

Shares of weight-loss drug makers Vivus Inc (NASDAQ:VVUS) fell ahead of an anticipated deadline by the end of Tuesday for the U.S. Food and Drug Administration to decide on approval of Vivus's diet drug Qnexa.

The stock of VVUS has seen heavy, volatile trade in the days leading up to the decision on the second of three new drugs aimed at tackling America's obesity epidemic.

The FDA last month approved a rival obesity drug called Belviq from Arena Pharmaceuticals Inc (NASDAQ:ARNA), making it the first prescription weight-loss pill to receive U.S. approval in over 13 years. In addition, there was also rumor of possible buyout from Pfizer (NYSE: PFE)

Share of Vivus fell 9.8 percent to $25.90 in early trading on the Nasdaq. They recouped most of those losses midday after a USA Today story appeared online saying the drug had been approved. The story quoted Vivus President Peter Tam saying it would be available to consumers later this year

The story was removed from USA Today's website about an hour later and replaced by a statement that the story had been prepared "in anticipation of FDA approval, but at this hour that approval is still pending." Vivus shares traded down 2.9 percent.

"The timing of the USA today report fits with (Vivus shares) recovering that 10 percent briefly," said Jonathan Aschoff, analyst with Brean Murray Carret & Co.
FDA officials were not immediately available for comment. Vivus declined comment.

Source: Reuters, Google images

Alnylam Pharma (ALNY)'s ALN-TTR02 able to knockdown TTR proteins by 94%

2012-07-16T21:39:00.002-04:00

Alnylam Pharmaceuticals Inc. (ALNY), the developer of a treatment for a rare genetic disorder, rose the most ever after the drug showed promise in an early clinical trial.

Alnylam Pharmaceuticals Inc announced the achievement of positive clinical results from its Phase I trial with ALN-TTR02, an RNAi therapeutic targeting the transthyretin (TTR) gene for the treatment of TTR-mediated amyloidosis (ATTR).

My analysis: As the pharmacogenomics and personalized medicine are coming in the forefront the companies like Alnylam Pharma (ALNY) are benefiting a lot from it. Due to smaller market capitalization of these companies, they tend to rise exponentially on positive press release.

I feel this rally will not last too long before investors realize that this is just the Phase I trial data which are mainly toxicity data. This data may get presented at various investor conferences but this drug still has lots of clinical inspection to go thru.

This company is certainly not a M&A target due to its specific focused pipeline. It will be intersteing to see in coming months how this company pans out.

TTR medicated amyloidosis

The disease is caused by a mutation in the gene responsible for producing the transthyretin protein. In people with the genetic defect, transthyretin made by the liver breaks apart, forms into clumps, and damages the nerves and heart. Currently a liver transplant is the only available treatment.

Alnylam’s drug, called ALN-TTR02, stops production of transthyretin. The company is focusing on patients with TTR-FAP, or transthyretin familial amyloid polyneuropathy. The company estimates that as many as 10,000 patients have the disease. In TTR-FAP, the protein attacks the body’s longest nerves first, often killing them within a decade as the body shuts down.

Results from this study show that administration of ALN-TTR02 leads to robust knockdown of serum TTR protein levels of up to 94%; the overall results were highly significant (p<0.00001 by ANOVA). Suppression of TTR, the disease-causing protein in ATTR, was found to be rapid, dose dependent, durable, and specific after just a single dose.

Alnylam recently reported that it has initiated a Phase II study of ALN-TTR02 in patients with ATTR and has guided that its goal is to start a pivotal trial in 2013.

The primary objective of the study was to evaluate the safety and tolerability of a single dose of ALN-TTR02, with subjects being enrolled into five sequential cohorts of increasing doses ranging from 0.01 to 0.50 mg/kg. In addition, pharmacodynamic activity was evaluated with serial measurements of serum TTR protein levels through at least day 56.

Preliminary data from this study showed that a single dose of ALN-TTR02 resulted in rapid, dose-dependent, durable, and specific knockdown of serum TTR levels. Even at doses as low as 0.15 mg/kg, substantial serum TTR suppression was achieved, with a mean 81.9% knockdown at nadir.

Sources: Reuters and Bloomberg

Welcome to a6

2012-07-14T18:45:00.001-04:00

My name is Ankit Desai. I am a 4th year PharmD candidate at UNC School of Pharmacy in Chapel Hill, NC. I have a great interest in Healthcare and Biotechnology Drug Research and Development. I enjoy learning about innovative drug candidates in late stage clinical trials and ones that are already on market.My main interests include oncology ,cardiology and neurology drugs. Along with learning about late stage clinical drug candidates, I also try to find investment opportunities in publicly traded biotech/pharma companies that I cover. In my opinion, you can generate good return on your investment if you do proper due diligence.

With this blog, I am planning on focusing and various late stage drug candidates and writing a research report on them. Not only this will help me learn more about the innovative products but it will also give my audience (you) a chance to see how drugs come market and what it takes to bring a chemical entity from lab bench to pharmacy counter. All the opinions expressed in this blog are solely my own opinions.

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A6 research or “a6research.blogspot.com” is not an investment advisory service, nor a registered investment advisor or broker-dealer and does not purport to tell or suggest which securities customers should buy or sell for themselves. The analysts and employees or affiliates of Company may hold positions in the stocks or industries discussed here. You understand and acknowledge that there is a very high degree of risk involved in trading securities. The Company, the authors, the publisher, and all affiliates of Company assume no responsibility or liability for your trading and investment results. Factual statements on the Company’s website, or in its publications, are made as of the date stated and are subject to change without notice. It should not be assumed that the methods, techniques, or indicators presented in these products will be profitable or that they will not result in losses. Past results of any individual trader or trading system published by Company are not indicative of future returns by that trader or system, and are not indicative of future returns which be realized by you. In addition, the indicators, strategies, columns, articles and all other features of Company’s products (collectively, the “Information”) are provided for informational and educational purposes only and should not be construed as investment advice. Examples presented on Company’s website are for educational purposes only. Such set-ups are not solicitations of any order to buy or sell. Accordingly, you should not rely solely on the Information in making any investment. Rather, you should use the Information only as a starting point for doing additional independent research in order to allow you to form your own opinion regarding investments. You should always check with your licensed financial advisor and tax advisor to determine the suitability of any investment.