Bear Sterns Summary of this weeks meeting:
Summary
Agouron hosted an analyst meeting yesterday, provididng updates for its three key compounds-Viracept, AG3340 and AG2034. In our opinion, the outlook for Viracept appears quite robust, while regarding AG3340 and AG2034 we are somewhat cautious. Below, we go over each of these in turn:
Viracept
Based on IMS and other data, we estimate that Viracept has about 28% share of the US protease inhibitor market, and that this share is still growing slowly. This translates into a $290 million run rate (as of October) in the US alone. What is more exciting, however, are Viracepts prospects for the future. Depending on the survey, doctors indicate that 8-13% of patients under care are on dual protease inhibitor therapy, but that 12-23% are expected to be on be on dual protease inhibitor therapy twelve months out. Currently, this translates 80% of the time to Invirase/Norvir used as a salvage regimen in those failing antiviral treatment. However, with additional data, we believe
that Viracept will participate to a greater extent in this expansion of the market. We also note that today, Viracept is the clear drug of choice for patients and physicians initiating traetment with a PI for the first time. 90% of physicians surveyed (admittedly by Agouron) indicated they plan to expand use of Viracept in 1998, while between 30% and 40% indicated similiar sentiments for Crixivan, Invirase and Norvir. While we are not enthusiastic about either Crixivan or Viracept twice daily regimens, we note that interim data from the Viracept study intended to support a sNDA should be available in Febuary.
AG3340
This compound is Agouron's selective matrix metalloprotease inhibitor (MMPI), set to begin combination studies with Taxol in non-small cell lung cancer and Carboplatin in hormone refractory prostrate cancer patients in 1998. MMP activity is important for primary tumor growth, metastasis (cancer spread) and angiogenesis, although certain members of this family of enzymes play specific roles. For example, gelatinase A is important in angiogenesis, but collagenase (a related MMP) is important in the day-to-day maintenance of joint integrity. Therefore, MMPIs that hit both of these enzymes can yield both anticancer effects and joint stiffness as a side effect. AG3340 is selective for the enzymes implicated in tumor growth and could therefore have a therapeutic window in which to provide anticancer effects without joint stiffness, etc. Thus far, in clinical trials lasting several weeks, the 5mg twice daily dose of AG3340 has yielded such a profile. Despite this, we remain cautious regarding AG3340. There is an obvious therapeutic window to the drug (10mg twice daily began to yield some adverse events) and we do not yet know the magnitude or duration of anti-tumor response at the best tolerated doses or in a variety of tumor/patient types.
AG2034
Tumors rely on what is known as the "do novo" purine pathway for growth. This biochemical process involves several enzymes, including GART, of which AG2034 is an inhibitor. For this reason, AG2034 is more toxic to cancer cells than normal cells. What is also very interesting about AG2034 is that it selectively kills cells which lack a protein known as P53. About 70% of colon cancer cells lack P53 and about 50% of all tumor types lack P53, although all normal cells are P53 positive. It has been shown that patients with cancer cells lacking P53 are much more likely to die than are those with P53 positive cells (e.g. 3 fold more likely in colorectal cancer). Therefore, there is much reason to believe AG2034 could be a very effective anticancer agent. At present, Agouron is wrapping up a Phase I dose-escalation study in which AG2034 is given as a one hour infusion every three weeks. In this study, fatigue and blood cell toxicity appear to be the limiting side effects, although it is not yet known what the safety/efficacy trade off will be for longer-term studies. While we are intrigued by AG2034's mechanism of action, we believe any proof of commercial promise must come from efficacy studies which Agouron is now planning, especially in light of AG2034's potential to generate side effects. |
