Concerning epac: out-of-house combinations are "always and everywhere" tricky. I've used a parallel to SAP add-ons to show one model that works someplace for costly-costly combinations, but business software is a loooooonnnngg stretch from pharma. Until we see money flowing, I can't argue with skeptics who attach little value to epac. But one thing: if IDO inhibition is "a thing," epac has a big lead in maturity, and benign safety/tolerability.
Comparing recent analyst reports to older ones, I note that the value attributed to the Jakafi franchise against MPNs has dropped sharply (I think I've said it before--courage of one's convictions is an anti-survival trait for a sell-side analyst). I have a case that dropping valuations is wrong.
The old estimates were published before Jakafi turned in it's ~78% full year sales increase, which was not, to say the least, anticipated. At the earlier time, there was no reason to expect PV patients "adequately controlled" by less costly treatments to switch to Jakafi-now we know that many of them didn't agree that their disease was controlled adequately. The management estimate that 20% of PV patients were candidates for Jakafi was low; rather than an ultimate market composition of roughly equal numbers of MF and PV patients, it now looks like about 50% more PV. The standing management estimate of a $1.5 bln ultimate MPN market was made before the last 2 quarters of extraordinary sales growth. It's hard to estimate the top of a "stretched-out 'S' " adoption curve while you're in the steep part, but while adoption is accelerating (as it s now), it's realistic to guess that the peak will be more than twice the present rate (that's the bil an'a half). The potential competitive threat from pacritinib is gone; with a nasty peripheral neuropathy signal, momelotinib looks headed for strictly second-line use. I'm sure there are things other than pure business judgment at work, but Janssen's greatest money expectation with Imetelstat would be to drop the MPN target and go after MDSs exclusively (better chance of success, less competition, and most importantly, less chance of FDA holds as already-sick trial subjects have bad AEs). So effective competition for Jakafi is less likely than before. There are miscellaneous items to boost the MPN market: extra survival means higher prevalence, survival benefit of early treatment boosts addressables.
I wasn't talking about nastiness over continuing bullishness. I was anticipating "Sour grapes! Can't have life extension so now you're claiming it was about palliation." It ain't sour grapes. I was always looking more at palliation, and the story is there to be read. [Unfortunately, lack of life extension may put the payoff several years farther off]
And we have a first batch of semi-official "what went wrong"s. Basically, when the first trial subject got sick, there should have been much more information sharing RIGHT NOW.
I can just imagine imagine the nastiness coming my way, but the potential business completely lost with the cancellation of the phase 2s is modest. PLEASE search as far back as you can for "toxic cancer" and "cancer cachexia" in this board--I've had and stated the opinion underlying this topic since back when we called it '424ib.'
The main commercial opportunity for JAK inhibitors in solid tumors is (and at all times has been) to control paraneoplastic syndromes. It would have been a whole lot easier to get adoption of JAK inhibitors as palliatives if they also had a survival benefit, but we see that they don't. Paradoxically, the lack of a survival benefit may increase potential treatment duration because hospices are more receptive to use of drugs that don't promise life extension.
Safety and tolerability were secondary endpoints in Janus-1 and in the halted phase 2s. There was data collection and there will be analysis. There was sufficient trial duration for any effect to show up.
The only actual evidence bearing on whether JAK inhibitors affect solid tumor paraneoplastic syndromes that I have is the full presentation of Recap results, in which it was reported that treated subjects in the high-CRP subgroup gained weight. I don't have the journal publication [Dec 2015 Journal of Clinical Oncology (doi: 10.1200/JCO.2015.61.4578)], but I'll get it eventually. Weight gain in dying pancreatic cancer patients is, of course, extraordinary. I have learned separately that weight loss matters more to family and friends than to the patients themselves, but other aspects of paraneoplastic syndrome (like dependency) matter a lot to everyone. A large part of he morbidity in MF appears to be paraneoplastic syndromes, and unkind persons have suggested that relief of same is the main reason Jakafi is marketable.
Anyway, late this year there should be a read on the palliative value of ruxolitinib in solid tumors, and there may yet be a large market opportunity.
Sometimes it hurts to be reminded that Tefferi himself reported (in the online appendix to the NEJM paper) 48 adverse events of grade 3 or 4 among 33 subjects in a nominally 9-month trial (this may not include the1 grade 5 cytopenia with bleeding). That is not a record to stand on while predicting world conquest. (Similar statistics in a larger trial would probably force discontinuation).
Momelotinib has a record of association with poorly-reversible peripheral neuropathy, a hot-button issue with FDA and an equally large issue with patients.
Apparently there IS some notable read-out expected in April. The open label studies related to PI3K-delta inhibition may generate a proof of concept presentation at AACR. Not a whole lot of suspense (the concept has already generated candidates ELSEWHERE; the study allowed replacement of the Incyte candidate on the fly, and the new candidate is a purer reflection of the concept) B-cell malignancies are a desirable target, but enough treatment options exist so it'll take a lot more than a proof of concept to make investors' eyes light up. In contrast to the trials of ruxo against big 3 cancers, even overwhelming success wouldn't take Incyte into a different size category.
REALLY reaching for possible bad news:
The pattern for cancer immunotherapies is that they work for a relatively small fraction of patients, but have a relatively long period of effectiveness for the patients they help. In the phase 2 with Merck, the patients already treated are still being followed. In principle, duration of effectiveness could be lower than expected and jeopardize the phase 3. Only...it would pretty much have to be happening already to be meaningful (melanoma salvage patients don't have a real long life expectancy; the time since SITC is already substantial for them)
I haven't swept clinicaltrials, but I think all the trials that might have reported before June are gone. Next news items are likely to be the journal publication of the follow-up of the MF phase 3s, and the clinical plans dump in April. Neither one likely to generate price movement. "Other" epac phase 2s could come out any time, but we've been gently urged to expect them on a roughly 4-12 month time scale. Announcement of the plan for epac/pembro phase 3 also any time (but I'd guess April). For some reason, I don't expect it to generate much enthusiasm. Application to have N.I.C.E. reconsider Jakavi for MF should follow closely on publication of follow-up, but again, until it's in the can (June?) it's probably a yawn (I guess they could reject again, which would be a negative)
Anyone know the problem with low dose interferon in the US? Yeah, it's a possible competitor in MPNs by itself, but the combination with Jakavi looked miraculous.
Janssen going 100% for MDSs with IM maybe? Makes too much sense.
So maybe I care too much about corporate communication. During my second listen to the CC I tried to pick up any mention of how long it will remain available on the Incyte web site (I see no need for quarterly calls to go away EVER, and really, they stay useful for at least 13 months) (plenty of time to compare this year with last year). Transcripts are nice too, but slide decks just don't cut it.
Did you participate in the rumor campaign last Fall about ruxo patents expiring? That was disgusting.
If you want to understand this topic, look at other post around the same vintage
Take a moment Compare to previous CCs and those from other companies. What might have been there but wasn't? I don't recall anything but a chart appearance for the cMet inhibitor. No commentary around the 4% Jakafi price increase. I kind of expected a question about corporate communication policy. I was happy not to hear any new buzzwords.
Oh, in addition to the gorilla, there
s a feisty chimp in the room: the cMet inhibitor. I think Incyte is only in for teens royalties, but apparently it keeps chugging along toward market.
Ok, the actual sales numbers are super (they did warn that revenues reported in May are unlikely to grow quite as strongly).
Baricitinib is the 800-lb gorilla that everyone is ignoring. I can't see it having ultimate RA sales less than 1/3 of the anti-TNF market, and the non-failure of Xeljanz will make sell-in easier (they don't really compete with each other; both compete against anti-TNFs)
Epac remains the go-to companion IDO-1 inhibitor in immunotherapy combinations, but nothing else is as far along as the melanoma combo. But in melanoma, things look extremely promising. It sounds like Incyte is pre-recruiting locations to get the promised phase 3 a fast start. With success, there could be approval in 2017 (but commercial handling of epac is still a bit mysterious)
PI3K-delta is a validated target that has been shrouded by drug tolerability problems. Incyte's new entry looks like an important advance, and could go phase 3 in a year or so.
And just because Incyte is letting Novartis pull the plow on ruxo for GVHD, that won't prevent there being meaningful sales (say starting late Fall). It really is a condition where '110 would be preferable if it can be used at all, so it's reasonable for Incyte to put their trial effort there. A badly under-met need, with prevalence in the MPN range. I have a sad joke about one of the principal existing GVHD treatments: "watchful dying."
The 'broken pencils' chatter was edifying. What was left out was the fact that most analysts had already dropped their valuation of the ruxo in solid tumors program to zero (accompanying the CRC cohort discontinuation move), so instead of the stock paying for the discontinuation 3 times, it's paid 4 times. New specificity on bari participation-low end of the tiered range is 20% with an expected average of 25%. HH was clearly torn on whether to answer a question that amounted to whether bari will eventually sell over $6 Bln annually; I think he came down closer to yes than to no. (With the evident non-failure of Xeljanz, the vulnerability of RA biologics is clearer).
Since your mother has come up in this discussion, I'll ask whether she named you "reality_check_I" If not, you're at least as much a pseudo as I am. I say at least, because jacosa is pretty much my only online identity everywhere.