MDV3100 shows 4.8 improvement in median overall survival

Sally Church, PhD on Pharma Strategy Blog interviewed David Hung, MD CEO of Medivation and discussed the MDV3100 clinical trial data presented at ASCO GU.

Sally has been following the development of MDV3100 for a while, and previously interviewed Dr Charles Sawyers one of the co-developers.

MDV3100 showed an improvement in median overall survival of 4.8 months in advanced prostate cancer, and offers a number of significant advantages over abiraterone acetate (Zytiga) due to its different mechanism of action on the androgen receptor.

One of the advantages is it’s ability to target splice variants:

You can read more about MDV3100 on Pharma Strategy Blog.

Is ARN-509 more effective than MDV3100? 

Another interesting compound in prostate cancer drug development is Aragon’s ARN-509.  Recent research published in the AACR journal, “Cancer Research” suggests that ARN-509 may be a more potent androgen-receptor antagonist than MDV3100.

Whether ARN-509 will make it to market remains in question given that Medivation claim the compound was part of the intellectual property it acquired from UCLA along with what became MDV3100.

You can read more about the potential of Aragon’s ARN-509 in prostate cancer on Pharma Strategy Blog.

Radium-223 (Alpharadin) significantly prolongs time to first Skeletal Related Event

Pieter Droppert has written on Biotech Strategy Blog about the radium-223 (Alpharadin) clinical trial data presented by Dr Oliver Sartor at ASCO GU.

Alpharadin is a bone targeted radiopharmaceutical that has shown not only a significant delay in the time to first skeletal related event (SRE) but an increase in overall survival.

Dr Sartor kindly offered some clinical perspective on the data that you can read on Biotech Strategy Blog.

In case you missed it, the video interview with Dr Chris Parker at ECCO/ESMO 2011 in Stockholm offers further information on radium-223 and the ALSYMPCA trial results:

Amgen fails to convince ODAC that Xgeva should have a prostate bone mets indication

If you were following the prostate cancer news this past week, then the ODAC 12:1 vote against granting an indication for denosumab (Xgeva) for the prevention of prostate cancer bone metastases was in the news

Pieter Droppert collated the Xgeva ODAC meeting tweets on Storify if you are interested in what was live tweeted during the meeting.

Once Alpharadin is approved will radiation oncologists now get more involved in the treatment of prostate cancer and how will this impact the market dynamics? Will urologists favor MDV3100 that does not require administration of prednisone at the expense of Zytiga?

Companies will need to adapt their marketing strategy as new prostate cancer new products come to market in 2012.

Sally Church, Ph.D on Pharma Strategy Blog has reviewed some of the recent advances in our understanding of colororectal cancer (CRC).

Resistance to chemotherapy in colon cancer

The transcription factor AP-2 epsilon (TFAP2E-DKK4) appears to be responsible for some of the resistance to chemotherapy that occurs during colon cancer.

As Sally noted, “the presence of the TFAP2E-DKK4 mutation may explain why some patients with colorectal cancer do better with chemotherapy than others.”

Inflammation linked to the early development of colon cancer

Researchers from MD Anderson Cancer Center have identified the role of inflammation and silencing of tumor suppressor genes in early colorectal cancer.

Understanding the biology of the disease could lead to the ability to identify those at high risk of developing colon cancer. Chemopreventative drugs could then be given to this subset of high risk patients to delay the onset of cancer.  An exciting prospect!

Understanding the role of CIMP in early colorectal cancer

CpG island methylator phenotype (CIMP) can occur in 30% of colorectal cancer patients and has been shown to be an independent predictor of survival with 5FU in early or adjuvant CRC.   CIMP may play an important role in tumor development. Expect to hear more on the link between inflammation, DNA methylation and early development of CRC.

Identifying subsets of patients will support rational drug development

Researchers have now shown that BRAF(V600E) mutations occur in 8-10% of colon cancers. The ability to identify this subset of patients could allow therapeutic options to be specifically targeted at them, in the same way that ALK+ lung cancer patients now receive crizotinib.  Previously though, we didn’t know why vemurafenib was showing lack of efficacy in this group. New research has now given us some pointers.

As Sally noted on Pharma Strategy Blog, “a combination of vemurafenib and and an EGFR inhibitor such as as erlotinib, cetuximab or gefitinib, might be a useful clinical approach to try therapeutically in patients with colon cancer harboring the BRAFV600E mutation.”

As we learn more about the biology and early development of colorectal cancer, the ability to undertake rational drug development will increase.  This is good news both for patients and for biotechnology and pharmaceutical companies who want to successfully bring new products to market.

Today, an external hard drive offers a 1TB capacity; a few years ago the same product offered 100GB.  A 10x increase in storage capacity for the same money in the space of a few years.

Data is now available from online posters, abstracts, webcasts and presentations. We also have Facebook, Twitter, Linkedin and other social media competing for our time.

What this means is that if you plan to attend a major medical or scientific meeting such as the annual meeting of the American Society of Clinical Oncology (ASCO), which offers a lot of data, you need to have a conference coverage strategy.

Here are a few tips we suggest you consider:

Don’t go for a “Data Dump”

Too often we see a “fear of missing out” (FOMO) mentality drive a “we must capture everything” policy.  All this results in is a mass of data that somebody has to analyze after the meeting.  Too often a 300+ page data dump report (when it finally is produced) ends up sitting on the metaphorical shelf.

Focus on Key Questions

Prior to a major medical or scientific meeting it’s important to develop a list of the key questions that a brand, commercial or new products team need answered.  The questions could be on competitor activity, developments in a pathway or impact of clinical data on the standard of care.  Data collection can then be focusoned on answering those key questions.

Insights cost more

Recently, staff at a top 20 pharma company told us they were paying $X for a conference “data dump” but only had 10% of $X available for strategic insights.  In Twitter speak, they had #LostThePlot as it should be the other way round since insights are more valuable than raw data.

As management consultants, we might produce a Powerpoint slide with a table or chart based on data from 20 posters. In order to select those 20 key posters, we could have reviewed perhaps 200 posters originally.  Which would you rather have, one slide with insights and analysis or 200 Powerpoint slides with data? Our philosophy is “less is more.” 

Insights cost more because it takes in-depth therapeutic area knowledge and expertise to condense data into a meaningful story and make strategic recommendations.

What is your conference coverage strategy for this year? Please contact us if you would like to learn more about our capabilities.

Although many of the corporate presentations will be webcast over the next few days, it is expected that a lot of the news and commentary will be shared on twitter.

We are aggregating the #JPM12 tweets. If you are unable to be in San Francisco, you can follow the conversation below:

ASH 2011 Poster Session

Two Bruton’s Tyrosine Kinase (BTK) inhibitors in clinical development (PCI-32765 & AVL-292) generated a lot of interest at the recent American Society of Hematology (ASH) annual meeting in San Diego.

Sally Church on Pharma Strategy Blog has been following BTK as a novel drug development target, and saw its potential in early data presented at ASH 2010 and ASCO 2011.

Bruton’s Tyrosine Kinase is a critical kinase for lymphoma cell survival and proliferation. It plays an important role in B-lymphocyte development, differentiation and signaling. As Sally noted on Pharma Strategy Blog:

“It is a critical part of the BCL pathway that leads to cell proliferation, so targeting it leads to cell death or apoptosis.”

Sally’s insightful blog post goes into more detail on the Bruton’s Tyrosine Kinase clinical data presented at ASH by Dr Susan O’Brien (MD Anderson Cancer Center).

A number of companies are now taking an interest in BTK inhibition. Johnson & Johnson announced a $1B licensing deal for PCI-32765 just prior to the meeting. Sally’s analysis of this was:

“Based on the data seen over the last two years, I thought they got a steal”

BTK inhibition looks to be a promising target for B-cell malignancies such as non-hodgkin’s lymphoma (NHL), mantle cell lymphoma (MCL) & chronic lymphocytic leukemia (CLL). This is good news for patients.

BTK inhibitors are a new class of targeted therapies that we can expect to hear more about in the future.

ASCO 2012 is in Chicago from June 1 – 5

While everyone is busy making predictions about what the New Year will bring, we are already thinking about what are going to be hot topics at the 2012 annual meeting of the American Society of Clinical Oncology (ASCO).

ASCO is the largest and most important meeting of the year for those involved in oncology new product development and marketing strategy.

Predicting what will be hot at a meeting and when new trial data will be presented is not easy.  However, positive or negative data from a major clinical trial can have a huge impact on a market or in the case of new products in development, the market potential.

Prior to ASCO 2011, Sally Church produced the following preview video. It’s still worth watching if you missed it the first time round.

Sally has already started working on her list of what may be hot at ASCO 2012 in preparation for this year’s video.

On Pharma Strategy Blog yesterday, Sally discussed the recent results for the VEGF inhibitor tivozanib (AVEO/Astellas) in advanced renal cancer (RCC).

Tivozanib showed a greater progression free survival (PFS) compared to sorafenib, but “the sorafenib arm did better than expected,” noted Sally.  You can read more analysis about what this means on Pharma Strategy Blog.

The tivozanib data has been submitted as an abstract for ASCO this year (abstract deadline is February 1st), leading Sally to conclude that:

“This year’s ASCO is going to be a most interesting meeting for renal cell cancer.”

Time perhaps to starting making your New Year predictions of what may be hot at ASCO in 2012?

What was hot at ASH in 2011?

In her pre-conference post, Sally Church on Pharma Strategy Blog outlined what she thought would be hot news and interesting data at ASH in 2011.

Amongst the topics she selected were:

• CML: updated phase II PACE trial results for ponatinib

• Myelofibrosis: updated phase III data from COMFORT-1 trial of ruxolitinib

• Myeloma: 5 year data from VISTA trial that compares the combination of Velcade, melphalan and prednisone (VMP) with melphalan and prednisone (MP) alone

• Lymphoma: the CD20 antibody obinutuzumab (GA101).

Sally also mentioned in her pre-conference post a few other compounds likely to be interesting in lymphomas such as the Bruton’s Tyrosine Kinase Inhibitor PCI-32765 (Pharmacyclics) and the aurora kinase A inhibitor, alisertib (Seattle Genetics).

What were your predictions pre-ASH 2011?

It’s not easy to analyze a conference program that contains over 4000+ posters and predict what is going to be a hot topic, and commit to this in public in advance!

To do so requires an understanding of new products in development, mechanisms of action, prior clinical trial results and the impact positive or negative data may have on the standard of care.

If you went to ASH 2011 – how do you think Sally’s predictions stacked up?  Sally will be writing her own retrospective assessment in due course.

Although the San Diego weather was much wetter and cooler than expected, there was a lot of interesting data presented at ASH this year that more than made up for it.

Review #ASH11 Twitter Coverage

If you want to read what others thought was hot during the meeting, the #ASH11 tweets have been aggregated on Pharma Strategy Blog.

This study combined two anti human epidermal growth factor receptor 2 (HER2) monoclonal antibodies, trastuzumab and pertuzumab with docetaxel.

Results showed a median progression-free survival of 18.5 months in the pertuzumab plus trastuzumab plus docetaxel group as compared to 12.4 months in the control group that received placebo plus trastuzumab plus docetaxel.

In other words the addition of pertuzumab improved PFS by 6.1 months.  As Sally Church writing on Pharma Strategy Blog noted in her second update from SABCS, this is “another stunning six month leap in survival.”

The two monoclonal antibodies have different mechanisms of action and as Sally discusses in her post,

“the idea behind combining pertuzumab and trastuzumab upfront is to enable a more comprehensive shutdown of the HER2 pathway and delay the resistance setting in.”

You can read more on Pharma Strategy Blog. There was a lot of new data presented at the San Antonio Breast Cancer Symposium this year, and seeing the improvement in patient survival from BOLERO-2 and CLEOPATRA is what all those involved in the industry live for.

Sally poignantly describes this in her summary of SABCS:

“This year’s San Antonio Breast Cancer Symposium was very uplifting and one of the more exciting meetings of the last five years.”

Please contact us If you are interested in learning more about the breast cancer market and the impact new products in development such as the antibody drug conjugate T-DM1 and HDAC inhibitor, entinostat may have.

José Baselga had previously presented the impressive results at ECCO/ESMO 2011 in Stockholm.

As Sally Church noted on Pharma Strategy Blog in her second update on “what’s hot at SABCS”:

“The trial data presented by Dr Gabriel Hortobagyi (MDACC) confirmed that the responses continue to be durable, with an improvement in PFS with the combination arm now up to 11.0 months, up from 10.6 months at ECCO. The results for the exemestane control arm remained at 4.1 months.”

The extra 6.9 months of survival benefit shown with exemestane plus the mTOR inhibitor everolimus is good news for advanced breast cancer patients.

One of the problems associated with aromatase inhibitor (AI) therapy in breast cancer is that patients develop resistance over time.  As Sally notes,

“The rationale behind this trial is that mTOR is a known cause of resistance to AI therapy, so the combination targets both the estrogen receptor and mTOR adaptive resistance pathway.”

You can read more on Pharma Strategy Blog about the BOLERO-2 trial presented at the San Antonio Breast Cancer Symposium and why this was a rationally designed study based on solid science.

Deserted River Walk due to San Antonio cold weather

If you are interested in news from the San Antonio Breast Cancer Symposium (SABCS) then Sally Church, PhD has a number of reports on Pharma Strategy Blog that are worth reading.

SABCS Video Preview

In her preview of the SABCS meeting (that you can also watch below), Sally reviews some of the BOLERO-2, CLEOPATRA and NEOSPHERE clinical trials, and what impact positive data may have on breast cancer patients. It is well worth watching.

SABCS Twitter Coverage

Although there is no wifi in the meeting rooms at SABCS, a few scientists, patients advocates and physicians are tweeting from the meeting including @drsteventucker and @teamoncology. You can easily follow the twitter conversation and check-out what’s been said through the #SABCS aggregator on Pharma Strategy Blog. As Sally would say, “check it out!”

As an example of how effective social media can be to share information, Pieter Droppert (@3NT) used storify to share some of the insights posted on twitter during the SABCS plenary lecture he attended on potential of macrophages as breast cancer drug development targets.

Breast Cancer and the Environment

Pieter also commented on the recent Institute of Medicine (IOM) report on “Breast Cancer and the Environment” which was somewhat disappointing to those hoping that it would highlight causal links.

Hot news at SABCS 

This year the San Antonio Breast Cancer Symposium had a lot of exciting new data. Two papers on the BOLERO-2 and CLEOPATRA trial data was published during the meeting.

Some of the interesting early data presented at the meeting included work on Notch inhibition to reduce aromatase inhibitor resistance, HER2 mutants and targeting HER3. You can read more updates from Sally Church on Pharma Strategy Blog.

Overall, this was one of the most interesting SABCS meetings of recent years with a good balance of science and clinical data.

Hopefully next year, there will be more discussants to put the data in context, as this would have made it an even better meeting.