Pharmaceutical Approvals Monthly from Elsevier Business Intelligence

Is The Time Finally Right For Bispecific Antibodies?

e.hayes@elsevier.com — Tue, 16 Apr 2013 13:55:00 -0400

Merck, Lilly, Gilead and Celgene are among the companies striking deals that involve bispecific antibodies. The novel dual-acting drugs have been in development since the 1980s with little success, yet big pharma believes they may finally be coming of age.

Surveying The Landscape Of Bispecific Antibodies In Clinical Development

e.hayes@elsevier.com — Tue, 16 Apr 2013 13:30:00 -0400

Bispecific antibodies that can target two different disease antigens with one molecule come in many different formats and could be applied to a range of therapeutic areas. Oncology and inflammatory disease are at the forefront of clinical development (see related story, "Is The Time Finally Right For Bispecific Antibodies?" — Pharmaceutical Approvals Monthly, April 2013).

Deal Activity Highlights Interest In Bispecific Antibodies

e.hayes@elsevier.com — Tue, 16 Apr 2013 13:28:00 -0400

Bispecific antibodies can be developed using many different formats for multiple therapeutic areas (see related story, "Is The Time Finally Right For Bispecific Antibodies?" — Pharmaceutical Approvals Monthly, April 2013). Big pharmas have inked deals with modest upfront payments to explore the use of a variety of technology applications.

Cyclacel Reports On Sapacitabine Program: A Fly In The Ointment?

m.goodman@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

Cyclacel has made progress on its pivotal trial of lead candidate sapacitabine in AML. But there are questions about its potency as a monotherapy based on an under-reported European trial in which the sapacitabine arm was stopped for futility.

Making A Market In Women’s Health: Endometriosis, Fibroids Emerge As Rx Targets

b.silverman@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

Candidates like AbbVie’s elagolix and Actavis’ Esmya promise oral therapy without the drawbacks of the artificial menopause induced by available hormone suppression therapy – and may pave the way for newer approaches while expanding the market.

Randomization Required: Liver Signal Necessitated Kadcyla Trial With Control Arm

b.silverman@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

A pivotal trial with a control arm was necessary to evaluate a hepatotoxicity signal with Genentech’s Kadcyla, helping to derail a bid for accelerated approval based on a single-arm Phase II trial. Genentech’s strategy of running trials in different lines of treatment concurrently enabled a quick strategy shift as an ongoing controlled Phase III trial in another line was amended to meet FDA’s regulatory requests.

Acadia’s Persistence With Pimavanserin In Parkinson’s Psychosis Pays Off

e.hayes@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

After meeting with FDA, Acadia announces it needs only one pivotal study for pimavanserin. The company has canceled a second study and expects to file at the end of 2014.

Amgen’s Melanoma Vaccine Shows Durable Response; Survival Still A Hurdle

e.hayes@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

The vaccine acquired from BioVex at high cost still needs to demonstrate overall survival in Phase III and prove value in an increasingly competitive market for melanoma treatments.

A.P. Pharma Puts Off APF530 Launch To 2014 After Another FDA Rejection

e.hayes@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

A.P. Pharma faces a second commercial setback as FDA issues another “complete response” letter for its long-acting granisetron in chemotherapy-induced nausea and vomiting.

Bayer Finds U.S. Not A Fertile Market For Pre-Menopausal Women’s Health

b.silverman@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

Bayer, one of the world’s largest women’s health firms, is looking East and South for growth in its women’s health franchise, shifting its attention away from mature markets in the U.S. and Europe.

Cyclacel Novel/Novel Sequence Promising In Tough Cancers

s.haley@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

The combination of two novel drugs from Cyclacel inflicts a form of synthetic lethality in which sapacitabine causes DNA defects, rendering tumor cells vulnerable to seliciclib, which thwarts the repair process and is lethal in its own right, the lead investigator reported April 7 at the American Association for Cancer Research meeting in Washington, D.C.

Kadcyla Manufacturing Review Was A Production In Itself

b.silverman@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

The complex manufacturing required by Genentech’s antibody-drug conjugate trastuzumab emtansine pushed FDA’s review two months past the agency’s internal action timetable, required four review teams from three CDER offices and produced a veritable blizzard of information requests. But is that level of intensity sustainable as the expanding ADC pipeline matures?

Yervoy/Zelboraf Combo Trial Fails, But Sequential Study Continues

e.hayes@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

Small Phase I melanoma study testing a combination of Zelboraf and Yervoy was closed early due to an unexpectedly high rate of liver toxicity, investigators report in letter to the editor of the New England Journal of Medicine. A sequential study of Yervoy and Zelboraf and other combination studies proceed as planned.

Fostamatinib Skates Through OSKIRA-1 With Mixed Results

e.hayes@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

AstraZeneca/Rigel’s oral SYK inhibitor fostamatinib met a key primary endpoint in the first of three rheumatoid arthritis Phase III studies, but missed another. Investors and analysts are underwhelmed with the efficacy results, although President and COO Raul Rodriguez advises holding on for the other Phase III trials before passing judgment.

Ironing Out the Fine Points Of Endometriosis Trial Design

b.silverman@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

Given the paucity of drugs to treat endometriosis and uterine fibroids, it is not surprising that FDA is still feeling out the regulatory standards. Neurocrine and Abbott are testing endpoints along the way.

March ANDA Approvals

Mon, 01 Apr 2013 00:00:00 -0400

Full and tentative approvals of generic drugs.

Pharmaxis Faces New Study Requirement For CF Drug Bronchitol

s.sutter@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

In a “complete response” letter, FDA says efficacy has not been adequately demonstrated for use of dry powder mannitol in cystic fibrosis patients ages six years and older.

Repros’ Proellex Is Poised To Enter Phase III – Again

b.silverman@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

Telapristone was put on clinical hold due to liver toxicity, but the company’s pursuit of vaginal formulation and re-analysis of the initial oral studies allowed the oral program to resume.

Ribavirin Sponsors Fend Off FDAAA Safety Labeling Changes, For Now

s.sutter@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

FDA said information about ribavirin-related drug resistance may have an impact on a class of investigational hepatitis C compounds in development but agreed with Merck and Genentech that labeling changes were not warranted “at this time.”

Ziopharm’s Future Uncertain After Poor PICASSO Results

l.lamotta@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

The oncology company ends development of its Phase III candidate in soft tissue sarcoma after progression-free survival data fail to live up to earlier expectations. The company will now refocus on its mid-stage pipeline.

Ado-Over: FDA Uses Prefix To Get Ahead Of Pull-Down Menu Problem

b.silverman@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

The use of computer drop-down menus organized by generic name was identified as a source of medication errors in the clinical program, mixing up Kadcyla with unconjugated trastuzumab. The solution of adding a three-letter prefix to Kadcyla’s nonproprietary name also seems to be the fix for biosimilars.

March Full Approvals

Mon, 01 Apr 2013 00:00:00 -0400

Full approvals of NDAs and BLAs.

March Supplemental Approvals

Mon, 01 Apr 2013 00:00:00 -0400

Chart lists efficacy supplements and labeling supplements selected by the editors of Pharmaceutical Approvals Monthly. This is not a comprehensive list of all supplemental approvals.

Estimated FDA User Fee Review Goals For Pending NDAs/BLAs

Mon, 01 Apr 2013 00:00:00 -0400

User fee goals are calculated based on the date of receipt. For applications submitted Oct. 1, 2012 and later, the timeframes are extended two months, to 12 months for standard review new molecular entitites and novel biologic entities and eight months for priority review NMEs and NBEs.

“Complete Response” Letters

Mon, 01 Apr 2013 00:00:00 -0400

FDA stopped issuing “approvable” and “not approvable” letters in favor of “complete response” letters on Aug. 11, 2008. The following chart lists “complete response” actions that were recently announced, as well as still-pending “approvable” and “not approvable” actions.

Kadcyla Reviewers

Mon, 01 Apr 2013 00:00:00 -0400

FDA staff that participated in the review of Genentech’s ado-trastuzumab emtansine.

Kadcyla Development Timeline

b.silverman@elsevier.com — Mon, 01 Apr 2013 00:00:00 -0400

A chronology of events leading to the approval of Genentech’s antibody-drug conjugate ado-trastuzumab emtansine.

2013 FDA Advisory Committee Recommendations

Mon, 01 Apr 2013 00:00:00 -0400

Year-to-date tracking of drug review recommendations from FDA advisory panels, including regulatory actions.

New Molecular Entities Approved In 2013

Mon, 01 Apr 2013 00:00:00 -0400

Annual listing of novel drugs cleared by FDA’s Center for Drug Evaluation and Research.

Biologics Approved In 2013

Mon, 01 Apr 2013 00:00:00 -0400

FDA transferred review of most therapeutic biologics to the Center for Drug Evaluation & Research in 2003. The Center for Biologics Evaluation & Research continues to review other biologics, including vaccines, cellular products, antitoxins and immunoglobulins.

Aubagio Approval Reflects FDA’s Evolving View On Multiple Sclerosis Drugs

s.sutter@elsevier.com — Tue, 19 Mar 2013 16:05:00 -0400

Sanofi’s teriflunomide is indicated broadly for treating relapsing forms of MS. The claim marks a departure from previously approved MS drugs, in which the specific effects seen in clinical trials are described in the Indications section.

Beyond Hormone Therapy: Signs Of Life In Pipeline For Menopausal Women

b.silverman@elsevier.com — Tue, 19 Mar 2013 16:03:00 -0400

Conditions associated with menopause represent a huge market, yet the R&D pipeline has long been slim, despite the well-known drawbacks of marketed hormone replacement therapies. But new approaches with a tissue-selective estrogenic effect are emerging: Shionogi’s Osphena for menopause-related sexual dysfunction broke the long drought in NME approvals, and Pfizer’s broad NDA for bazedoxifene/conjugated estrogens is under review.

Vertex Phase III For CF Combo Shows Power Of “Breakthrough” Designation

j.haas@elsevier.com — Tue, 19 Mar 2013 16:00:00 -0400

Pivotal trials for the combination of Kalydeco and VX-809 will measure safety and efficacy over 24 weeks, whereas Kalydeco monotherapy gained FDA approval on the basis of 56 weeks of data; Vertex and FDA developed the protocol together following a recent “breakthrough therapy” designation for the two-drug combo.

FDA Looked To Arava’s Safety Experience In Gauging Aubagio’s Risks

s.sutter@elsevier.com — Tue, 19 Mar 2013 15:30:00 -0400

Agency’s assessment of teriflunomide for multiple sclerosis incorporated the known safety data for leflunomide, a chemically related drug with an extensive post-marketing record in rheumatoid arthritis. Despite hepatotoxicity and other safety concerns with the older drug, its clinical experience provided reassurance that Aubagio’s risks could be managed without a REMS.

Aubagio Clinical Development

Tue, 19 Mar 2013 15:01:57 -0400

A timeline chronicling the development history of Sanofi’s teriflunomide.

Nuvo/Mallinckrodt’s Pennsaid Setback Starts Clock On Generic Launch

s.haley@elsevier.com — Fri, 01 Mar 2013 00:00:00 -0500

With Nuvo’s new Pennsaid 2% formulation hung up at FDA, Apotex may be able to launch its generic of the old 1.5% formulation of the topical diclofenac product on April 1, 2014, under a settlement announced in January.

Apremilast Efficacy Results Disappoint But May Be Enough For Commercial Success

j.haas@elsevier.com — Fri, 01 Mar 2013 00:00:00 -0500

Celgene’s PDE-4 inhibitor met the primary endpoint in the first of two pivotal psoriasis trials, but analysts worried that the treatment effect was less than that seen in a Phase II study. Some analysts see a niche for apremilast in treatment-naïve patients before they move on to biologic therapy.

Current Class Of Risk Evaluation & Mitigation Strategies

Fri, 01 Mar 2013 00:00:00 -0500

Here is a general outline of the REMS FDA has mandated so far, as well as a listing of drugs where it has been announced that REMS are being developed or drugs with safety issues that could invoke a REMS.

Aubagio Reviewers

Fri, 01 Mar 2013 00:00:00 -0500

FDA staff that participated in the review of Sanofi’s multiple sclerosis drug teriflunomide.

Heplisav’s Hopes For U.S. Approval Could Rest On Narrower Population

s.sutter@elsevier.com — Fri, 01 Mar 2013 00:00:00 -0500

In a “complete response” letter for the novel, adjuvanted hepatitis B vaccine, FDA cites the need for more safety data in the broad population of adults for which approval was sought; however, Dynavax says the agency appears open to considering a more restricted use, such as in patients with chronic kidney disease.

February ANDA Approvals

Fri, 01 Mar 2013 00:00:00 -0500

Full and tentative generic drug approvals by FDA.

February Supplemental Approvals

Fri, 01 Mar 2013 00:00:00 -0500

Chart lists efficacy supplements and labeling supplements selected by the editors of Pharmaceutical Approvals Monthly. This is not a comprehensive list of all supplemental approvals.

Regenerating Interest In Novel Drugs For Postmenopausal Osteoporosis

b.silverman@elsevier.com — Fri, 01 Mar 2013 00:00:00 -0500

New bone-targeted agents for osteoporosis must clear significant obstacles to succeed in a highly generic market, but safety concerns with established agents like bisphosphonates and calcitonin offer a foothold. Phase III anabolic candidates from Amgen and Radius Health aim to build new bone, the holy grail of osteoporosis treatment, but R&D in new anti-resorptive mechanisms to halt bone breakdown also continues.

Rhenovia Aims To Boost Biosimulation Use In CNS R&D

j.davis@elsevier.com — Fri, 01 Mar 2013 00:00:00 -0500

France's Rhenovia Pharma will recruit talent in the U.S. and Europe and offer its biosimulation techniques for use in developing drugs that target CNS disease, a previously difficult area for computer modeling.

The Medicines Co.’s Cangrelor’s Full CHAMPION PHOENIX Results Bode Well For Filing

e.hayes@elsevier.com — Fri, 01 Mar 2013 00:00:00 -0500

After two failed studies, The Medicines Co.’s rapid-acting I.V. antiplatelet drug reduces events by more than 20% in the Phase III CHAMPION PHOENIX angioplasty trial against Plavix. However, the company is already facing demand for studies against the newer and more potent antiplatelet drugs Brilinta and Effient.

AcelRx Marches Toward NDA Filing For Pain Drug-Device

j.merrill@elsevier.com — Fri, 01 Mar 2013 00:00:00 -0500

The specialty pharma is planning to file an NDA in the third quarter for its sublingual sufentanil NanoTab system for pain after the first of two pivotal trials reads out positively.

Orion Bionetworks MS Project Plumbs Big Data To Revitalize CNS Drug Development

s.haley@elsevier.com — Fri, 01 Mar 2013 00:00:00 -0500

A diverse group of public and private institutions has launched a precompetitive data sharing and predictive modeling effort called Orion Bionetworks, using computational biology to sift through imaging, genetic and biologic data from thousands of patients to identify the molecular underpinnings of multiple sclerosis and accelerate the pursuit of cures. Johnson & Johnson provided $5.4 million to fund the project.

February Full Approvals

Fri, 01 Mar 2013 00:00:00 -0500

Full approvals of NDAs and BLAs.

“Complete Response” Letters

Fri, 01 Mar 2013 00:00:00 -0500

2013 FDA Advisory Committee Recommendations

Fri, 01 Mar 2013 00:00:00 -0500

Year-to-date tracking of drug review recommendations from FDA advisory panels, including regulatory actions.