Biotech Values

[mcbio]

Re: R788 side effects

Neutropenia is a big issue too. Are you going to have patients on Neupogen and hypertension drug while taking R788? Its still not clear how the drug causes hypertension. If you don't understand the MOA, other unknown AE will pop up in the long run. You can argue that 90% of patients will be eligible for the treatment. However, FDA is now extremely anal on drugs designed for chronic use after viox, I just don't think RIGL will get a good deal in RA unless they do a 2 or 3 yea trials studying the long term effect of R788. Again I might just be biased since ARNA's Lorcaserin can not get a partnership even with positive phase 3 data.

I looked at their slides for the Phase 2a results again related to the primary dose they are carrying forward (100 mg bid). Neutropenia actually occurred in about 10% of patients. I believe the neutropenia was resolved just by lowering the dose of the drug (i.e., no other drug was needed). Hypertension occurred in about 4%. Again, I understand this was resolved by increasing blood pressure medication or by reducing the dose. Notwithstanding, you're right in that unknown AEs could pop up given longer duration clinical trials. It should also be noted that the drug is apparently contraindicated for pregnancy.

So, the drug clearly isn't entirely clean from a safety perspective. But, I think it has a legitimate place in a big market space, given that the side effects appear manageable. Longer-term studies will of course provide a definitive answer on this, but I think the Phase 2b results due next month will go a long way as one of these trials is a 6-month trial (the prior Phase 2a was just 3 months). I think this will give a partner enough confidence to pull the trigger if the results merit that.

Separately, I would just point out that R788 is a multi-indication drug and has also shown Phase 2 activity against a few lyphomas in Phase 2. Any side effects would presumably be much more acceptable in this setting. Plus, RIGL has a decent pipeline behind R788 so I think this helps to minimize risk.