Exelixis (EXEL) saw its share price cut in half last week, due to a regulatory setback. Based on what others have published and questions I received there appears to be some confusion with respect to the implications for the company. I decided to address this issue using a questions and answers format, based on the many inquiries I received. Hope this format sheds some light on the situation.
Last week BMS (BMY) increased its stake in BMS-936558 (formerly MDX-1106) by regaining worldwide marketing rights for the drug except in Japan, Korea and Taiwan. This was the result of a deal with Ono Pharmaceutical, who originally held ex-US rights for the drug. In return, Ono received marketing rights for Orencia, a BMS drug for Rheumatoid arthritis which is already in the market. BMS’ decision to exchange its stake in a product with real sales in return for a candidate in mid stage clinical development might seem odd at first glance, but a quick look at BMS-936558’s data is enough to understand the deal was a brilliant move.
Last week, Sanofi-Aventis (SNY) announced disappointing results from a phase III trial evaluating iniparib in breast cancer. The drug failed to improve survival and progression-free survival (PFS) in breast cancer patients and although actual data were not published, approval is unlikely even for a subset of patients. Failed phase III trials are quite common in oncology, a field with one of the highest attrition rates in the pharmaceutical industry. Nevertheless, iniparib’s failure is particularly disturbing, as the phase III was supported by compelling results from a randomized controlled phase II trial as well as strong scientific rationale. Importantly, this trial could have broader implications as it raises questions regarding the role of randomized phase II trials as a go/no go decision point for pivotal trials.
In the pharmaceutical industry, it is very common to see multiple drugs in development that go after the same target. Usually, there is a direct correlation between the recognition a target has and the number of competing agents. This is the case with “hot targets” such as PI3K,RAF and mTOR, which are pursued by many pharma and biotech companies.
In most cases (especially with targeted therapies), the different compounds are being developed in parallel, and there is no way of identifying a clear winner. This can persist even after approval. For instance, both BMS Pfizer and Novartis (NVS) have an mTOR inhibitor on the market for the treatment of renal cancer. It is clear both drugs are active but each compound was approved based on a different trial in a different patient population, so neither can claim superiority.
After a challenging year, Exelixis (EXEL) is finishing 2010 on a positive note, with the help of promising data for its lead agent, XL184. Last week at the EORTC conference, the company published data from a large phase II study in multiple cancer types. The results came at a crucial time for Exelixis, as many were questioning the value of XL184 following BMS’ (BMY) decision to opt-out of its development. As discussed in a previous post, when a partner like BMS dumps a late stage clinical asset after a licensing payment of over $150M, the alarm bells start ringing.
XL184 inhibits several targets, primarily VEGFR2 and Met. As a multi-targeted kinase inhibitor, the drug has some overlap with other drugs, primarily VEGFR inhibitors. There are two drugs that inhibit VEGFR (in addition to other targets) currently in the market as well as a long list of VEGFR inhibitors in late stage clinical testing from GSK (GSK), AstraZeneca (AZN), BMS and Aveo (AVEO). The main question regarding XL184 is whether the drug has a differentiated clinical profile in comparison to other VEGFR inhibitors. Based on recent data presented at EORTC the answer is a resounding “YES”. (more…)
Array’s (ARRY) shares keep on fluctuating in the $2.5-$3.5 range, relatively unchanged from the beginning of 2010. It seems that the market is having trouble assessing the real value of the company and its pipeline, which includes 13 (!) drugs in clinical trials. With a market cap of ~$170M, the market puts an average price tag of $13M per asset, a ridiculously low valuation (assuming no value is assigned to the company’s discovery platform). The company’s long term debt (due in 2014) could be partially blamed for this anomaly, but the problem seems to be more related to the company’s business model. The good news is that during the next year the company is looking at multiple events that might change the way Wall Street views Array. (more…)
Immunogen (IMGN) is still trying to recuperate from the controversial rejection of T-DM1’s accelerated approval filing. The message Immunogen was trying to convey is that nothing has changed in terms of T-DM1’s long term potential. According to the company, the FDA’s problem was not with the drug’s stellar activity but the patient population enrolled on the trial. In just over a week from now, it could have the data to prove it.
The FDA’s decision to reject Roche’s filing for accelerated approval of T-DM1’s had quite an impact on Immunogen’s (IMGN) stock. There is no doubt that T-DM1 represents the company’s most valuable, even if it is in the form of a mid single digit royalty rate, due to its blockbuster potential and impressive clinical activity. This justifies to some extent last week’s market reaction, as the next potential approval for T-DM1 will is anticipated in mid 2012. Nevertheless, T-DM1 is facing multiple potential value creation events in the coming year, including an important data set for T-DM1 next month. In addition, the company is involved in 6 clinical stage programs (#7 is expected to enter the clinic this month), some of which are expected to generate data in the coming months. Although none of these programs are nearly as exciting as T-DM1, some of them could become more attractive with time.
Last week, Roche announced that the FDA was unwilling to accept T-DM1’s accelerated approval filing for breast cancer, sending Immunogen’s (IMGN) shares tumbling almost 40%. The filing was based on impressive results from a single arm phase II trial in 3rd line HER2 breast cancer. Typically, gaining regulatory approval requires a large, randomized phase III study but in cases of highly unmet need where patients are bereft of effective treatment options, the FDA may consider approval in a limited patient population.
Yesterday Pfizer (PFE) announced that Sutent failed to prolong survival of lung cancer patients when given in combination with Tarceva. The drug led to an increase in progression free survival (PFS), which was the secondary endpoint of the study. The results are not published and there are several open questions such as the extent of PFS improvement, benefit across different subtypes and use of Sutent in patients from the placebo cohort after progressing on Tarceva. Nevertheless, chances to see Sutent+Tarceva as a standard of care for 2nd/3rd line NSCLC are slim.
Pfizer’s failure provided some clarity for Arqule (ARQL) and its partner Daiichi Sankyo, who plan to initiate a phase III study for ARQ-197 in combination with Tarceva. The indication Arqule is pursuing is very similar to that pursued by Pfizer, so had the Sutent trial been successful, it would have adversely affect ARQ-197’s prospects in general and potentially the required clinical route. (more…)
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