CP-690,550: Phase 2b data evaluating the activity of Pfizer’s small molecule JAK-inhibitor, CP-690,550 in combination with methotrexate in patients with rheumatoid arthritis will be in a late-breaking presentation by Dr. Joel Kremer, professor of medicine and head of rheumatology, Albany Medical College on Tuesday, October 28.
CP-690,550: Phase 2 data evaluating the tolerability and safety of JAK-inhibitor CP-690,555 in patients with moderate to severe rheumatoid arthritis will be presented by Dr. Carol Connell, associate director, Pfizer Inflammation Research Division on Sunday, October 26.
CP-690,550: Phase 1 results from a trial assessing the tolerability of oral JAK-inhibitor CP-690,550 with methotrexate in patients with rheumatoid arthritis will be presented in a poster session by Bethany Wilkinson, associate director, Pfizer Inflammation Research Division on Sunday October 26. <<
>>We'll see about the safety issues surrounding Rigel's R788. Given that it's a novel drug and works via a different mechanism than PFE or INCY's compounds, I think there's more of a safety margin. Also, the hypertension concerns appear to be overblown.<<
For what it's worth ...
"I thought the Pfizer data looked pretty good. I thought the Rigel data was pretty unimpressive, especially when you consider the tox issues they're dealing with, with the GI stuff in particular, going down even to the low relatively ineffective dose."
The field is getting crowded ...
>>Corporate JAK Inhibitor R&D Pipelines
Eli Lilly (SGX Pharmaceuticals)
Johnson & Johnson
Ligand Pharmaceuticals (Pharmacopeia)
We'll see about the safety issues surrounding Rigel's R788. Given that it's a novel drug and works via a different mechanism than PFE or INCY's compounds, I think there's more of a safety margin. Also, the hypertension concerns appear to be overblown. See:
As I am long RIGL, I'm curious to hear any opinions regarding the safety of R788.
>>and with rigel's prospects looking dimmer, i'm surprised the mkt doesn't see value and potential advantage in incyte's cmpd<<
Why do you think it doesn't?
Clearly Incyte's stock price is being hit more because of the cash/debt/capital markets situation than because people are concerned about their pipeline. They have ~$422M in debt! Incyte certainly has some burn runway, but if they don't raise significant cash during the next year (perhaps through outlicensing), the situation could begin to look more dire ...
Speaking of outlicensing, the Pfizer CCR2 outlicensing has been a huge disappointment. $40M upfront but what happened to the rest of the $800M (potentially) and the huge number of indications??? As I recall, Incyte was in multiple Phase II's at the time of the outlicensing, and none of those programs has gone forward, as far as I can tell. Pfizer is just beginning a new Phase II in ... osteoarthritic pain??? Wish management would clarify what happened there. The silence is deafening!
There is yet another oral RA drug candidate in trials. However, the target is novel and not Rigl's, nor Incy's, nor Pfe's. LX2391 will enter drug to drug interaction studies in RA patients first quarter of 09 after successfully completing all phase one studies.
The compound regulates lymphocyte trafficking:
>>LX2391 will enter drug to drug interaction studies in RA patients first quarter of 09 after successfully completing all phase one studies.<<
Wake me up when they get some ACR70's or 90's.
Also INCY has their financing in place for at least a year, management was smart to raise 100 million a few months back. They sold 12m shares @ 9.00, and you can buy today under 4.00, come on, thats bargain basement prices. Also thinking about buying a position in Amylin, but will wait because its in free fall mode.
I agree, I see value, I bought some INCY this morning, looks like they are throwing in the towel on Rigel. Nobody wants these small and mid cap biotechs, I just bought some Biomarin at 14.90. I repeat, 14.90. That is a steal if I ever saw one. That goes back to when they announced phenoptin(Kuvan) phase 3 data in March 2006.
If Pfizer's cmpd is a pan Jak inhibitor, it is important, because 18424 is NOT. They have stated many times that it is highly selective for Jak1/2 and not 3. It is believed by many that the side effects, seen by PFE and RIGL, come from inhibiting Jak3.
Pfizer encountered some serious infections (hypothesized as due to JAK-3 inhibition) and changes in liver enzymes (a mystery), neither of which Incyte saw. The liver enzymes problem is often enough to end a me-too drug development program; for the first oral agent comparably effective to TNF binders, they'll probably try to manage it. If Incyte could promise that the difference was real, they'd have a huge edge.
Incyte's hypothesis concerning neutropenia is that anything interfering with IL-6 activity (like a JAK inhibitor) allows a higher level of margination (which I had to look up). In effect, it isn't real neutropenia, it's a change in sampling behavior. The neutrophils are still there to do their jobs, but fewer of them are circulating freely.
By dose-response, I mostly mean that 15 mg BID seemed to get more response than 25 mg BID. Not a big shock in a tiny trial like this one, but it reminds viewers how big the error bars should be.
>>Skeptics are holding in reserve the objections that the lack of a dose-response curve leaves open the possibility that the results were random<<
If you look carefully at the slides, there is no way that the results are "random". The 15 mg BID, 25 mg BID and 50 mg QD doses (similar to 25 mg BID!) show very different results from placebo. The 5 mg BID (only 1/3 the dose of 15 mg BID) looks a lot like placebo, but so what?
>>the relative freedom from side effects may also be random so they should allow for side effects as bad as Pfizer has seen <<
I don't think there is sufficient info to compare AEs for the two drugs. Was any neutropenia seen with the Pfizer drug?
The reason for the stock price drop is apparently that the results showed nothing really new from what Incyte has disclosed previously. It is clear that Pfizer is ahead and Incyte's drug has no obvious differentiating characteristics at this point. But the big problem is that small, leveraged, cash flow negative biotechs are no longer in the driver's seat with respect to Big Pharma. Big Pharma has drugs expiring, but they also have cash - a lot of cash - and right now cash is king. Incyte will not get the sort of outlicensing deals they might have gotten a few months ago. At least not for another year or two.