I think it's INCY's first membership in an index that's tracked by a fund of substantial size. So it adds an owner that is hard to #$%$ on a day-to-day basis.
Nice. But May I suggest exiting gradually? INCY is a good candidate for a "January Effect" bump. (Have we just seen January in December? I think it's one of the seasonalities that has a good reason for happening when it does, so even if part of it has shifted, there's logic behind expecting some to stay put)
Nov/Dec is close enough to Fall. We know pretty much what the outcome will be: spleen reduction meets primary endpoint and constitutional signs greatly improved. Management opines that 20% of PV patients are sick enough that Jakafi might be appropriate, although that seems high.
When I speak of PaCa in a short time frame, Ruxo is implied. '110 is too far in the future, and since it isn't registered, there's no question that studies have to be designed with registerability as an early goal. PaCa is so dramatic that an already-registered drug would have a good chance of attracting off-label use.
I see nothing about FDA having granted IM any sort of fast-tracking. Clinicaltrials.gov shows a number of arguable p2 trials of IM, mostly suspended. None of the designs look especially compatible with expansion of the recent ASH results. I will accept your number of 375 patients--one case of aplastic anemia among 375 exposed patients would make a drug very unlikely to gain registration, so it will be necessary to set protocols that show the event was an anomaly, or at least completely avoidable.
Note that cure is not claimed. Also note that Tefferi has excellent rapport with patients (great in a clinician, not so great when assessing unreviewed public statements).
Jakafi probably gets PV onto the label come Fall. The GP vs hem/onc mix of treating physicians is a lot different for PV vs MF. It isn't at all clear that the specialty pharmacy distribution model will go over as well. A lot more judgment is needed to select PV patients who might be better off getting Jakafi (vs MF patients). Think there'll be a need to expand the sales force? If selling is too good, might there be a backlash (e.g. nearly all PV patients have JAK response mutations; could high prescription volume cause insurers to limit coverage in MF to only those patients with JAK response mutations or something like that?)
It's entirely possible that the follow-up study on Ruxo in PaCa starting this Spring could support label expansion. It would be faster and require fewer subjects not to create an opening for that. Relatively little of the potential market depends on bringing the indication on-label; success alone would do most of the job. The benefit of having PaCa on-label is that the company (and especially salesmen) can talk freely. We HAVE seen the benefit of keeping the company publicly in the conversation in the refinement of Jakafi dosing. Any comments on the trade-off? I personally favor the smaller, shorter study (but I've always over-estimated off-label sales possibilities).
There was supposed to be an announcement in June. The trial is structured in a way that could end quickly or drag on, and they were supposed to tell us which. Absent a statement from the company, this is unknowable.
Golly that's fun. But it's up to 20 replies and it's getting hard to follow.
I admit to having been surprised by the flat statement at the Oppenheimer conference that Jakafi doesn't cross the blood-brain barrier. Jakafi is relatively lipid soluble, which tends to increase likelihood of getting across. But there are a variety of active pumps kicking foreign molecules out, and apparently they catch Jakafi.
VERY rough rule of thumb: a drug given in a total amount of under 100 mg a day is unlikely to have off-target toxicity. There certainly haven't been reports published that suggest off-target toxicity of Jakafi.
I don't think I said anything inflammatory. Anyway, they seem to be having so much fun arguing among themselves that pretty soon this distraction will grow old.
COX-2 was significantly different. The toxicity was, let's call it "near-target." There are a bunch of pretty similar cyclooxygenases, Inhibiting COX-2(s) in preference to COX-1(s) spares the stomach, but it turns out that at least one COX-2 prevents minor blood vessel damage from setting off significant clotting. Safety became a question of fine tuning degrees of inhibition of very similar enzymes.
Here' we're looking at a completely off-target effect. Sanofi's drug is given in a large-ish dose and affects enzymes outside the JAK family.
Hey, someone told me that I had been mentioned here. I'm flattered. Maybe I should start a market advisory letter to capitalize on the fame.
Ok, Dan is confused. The Sanofi trial was stopped for a high incidence of Wernicke syndrome (which can induce headaches because of eyestrain--this is the collection of symptoms seen in severe alcoholics that makes them appear drunk even at 0% alcohol, and in alcoholics is caused by vitamin B1 deficiency combined with increased need for the vitamin)(The confusion was certainly abetted by the announcement calling the AE 'Wernicke's encephalopathy.' which SOUNDS like it should have lesions). It has been stated explicitly that Jakafi doesn't cross the blood-brain barrier. Wernicke syndrome in early stages is entirely functional, with no actual lesions. Google this stuff if you don't believe me.
Thinking more about it, because Sanofi's compound is structurally distinctive, it may be worth their while to try to salvage it. So in a year or two, we may hear exactly how it causes Wernicke's syndrome, and a study may start on how to avoid it. Not of business interest to Incyte holders.
Where do you get those numbers? I don't think that level of detail is available for Jakafi in the wild. The reported AEs of Jakafi treatment are overwhelmingly those of anemia and thrombocytopenia (for example black tarry stools are generally caused by intestinal bleeding, a complication of thrombocytopenia), and revised dosing has been helpful.
We are almost 100% sure that Sanofi's problem was an off-target toxicity. And not so much lesions as a functional adverse effect. I'm not sure that anyone cares enough to track down the exact mechanism of the side effect, but the guessing has been that intestinal effects unique to Sanofi's drug prevented absorption of thiamine from food. The incidence was enormous in the treated population. You couldn't miss even 1/5 that incidence.
I'm unlikely to learn much new from a blog by one of Tefferi's patients. By all accounts, they idolize him. But y'know, N=1. And even the patients he treats with hydroxyurea idolize him. And those patients improve, both in lab results and how they feel, while other hem/oncs basically break even with that drug. The man should treat patients and keep his typewriter closed.
I'd REALLY like a link to that review. Fatigue, thrombocytopenia and anemia are well-known AEs with Jakafi, and are manageable (note that despite the thrombocytopenia, Incyte representatives have stated that there have been no life-threatening bleeds). I'm pretty sure that if brain lesions were "commonly reported" we'd have heard of it before--one possibly-associated case of PML sure made a splash. Breathing difficulty is a little vague; I'd like to consider it secondary to other AEs, like anemia and pneumonia. Pneumonia is the interesting item on the list. JAK2 inhibition reduces the number of granulocytes produced (most importantly neutrophils, but other classes too) and JAK1 inhibition blunts immune response. All through testing and early adoption there was a lot of surveillance for opportunistic and/or rapidly-progressing infections. Nothing spectacular showed up. At the last analyst presentation, a hint was dropped that some sort of infection signal is being seen; that will certainly be followed up.
The problem with treating ET is that for most patients, the experience is fatigue and itching. The disease does not reduce average life expectancy. A small fraction of patients are much sicker, but not many. A 2-hour intravenous drug administration every other week is arguably as disruptive as the illness itself. Any risk at all of causing aplastic anemia is unacceptable. Any candidate treatment will have to go through a biggish trial to set an upper limit on rate of leukemic transformation.
A. Tefferi is a superb clinician. The personality traits that destroy him as a scientist don't harm that, and may even help. Patients, from what I have gathered, adore him. The only downside I get from gossip is that he sometimes tells patients that they're better based on lab work when they definitely don't feel better.
As for prognosis with Jakafi, it improves every time there's a clinical update.
My prediction that IM will not affect Incyte's business in a way we ought to care about has only the tiniest bit to do with science. Only if the ASH results were such a slam dunk that FDA was likely to shove procedure aside was there any chance of such a thing happening, and even the abstract from way back when showed that things weren't so spectacular. Take away Tefferi's editorializing and the full presentation was somewhat weaker than the abstract.
The prediction has a lot more to do with looking at investor behavior and analyst opinions for rather a while. A merely good ASH presentation might affect GERN, but wouldn't be expected to affect INCY.
I'm pretty sure he shorted Geron based on the company's long history of disappointing investors. That may have been misguided, as there as been a management shake-up since the last catastrophe, but many of us have seen both kinds of management changes.
I didn't used to know anything about Geron, but I've picked up at least a little. It seems unlikely that the company can survive as an independent. As a takeover target, you can't assign much value to the prospects of IM against essential thrombocythemia (the cure looks worse than the disease, and it'll take a lot of data to disprove that). I'll look at the rest of the company the way I have looked at Incyte in the past: management and long-term holders clearly think IM is very valuable. Right now, a potential acquirer is going to see it as having a large risk of failing in p2 (there may be no dosing schedule that can be given explicitly that offers attractive risk::reward). That doesn't have to be true, but it's what a potential acquirer has to 'fade.' Nothing other than the IM program looks valuable. So I don't think a price can be agreed upon until a p2 is completed. There appears to be just about enough cash to get there.
ONLY a rookie investor would think a stock should react because there is a chance that the company's main product MIGHT have competition more than 3 years in the future.
BA Harvard PhD Northwestern Former U of Chicago faculty "Scientific brother" of Robert Grubbs. Somewhat-respected gadfly in celiac disease research. I'm in Who's Who.
I feel so dirty.
Now go the @#$%^ away.