I had been looking forward to a readout in January, but 3 months ago the primary completion date was moved to April. At the time, I shrugged and said "pancreatic cancer trials are hard to fill with all the candidates around." Now, with too much time on my hands, I'm considering another possibility.
September would be around button-up time for the futility/slaughter analysis (which I guestimate started late June--such things are rarely announced unless they call for an end to the trial). The Clinicaltrials entry on Janus 1 says that data will be collected as long as there are eligible (read that as living) subjects. So this fits with a survival advantage (less than the slaughter threshold) seen at the midpoint. The trial is slightly over-powered, not by so much that there was real hope of termination for slaughter, but enough so that a survival benefit on the order of the length of the trial extension (or even a month less, to allow for the possible slow recruitment) would meet the objective (unless the controls are also doing much better than expected...that happens sometimes).
So anyway, I'm taking this as a hopeful sign and nudging my guess at the probability that Janus 1 will succeed from 75% to 89%
We're now in window dressing season, which ought to be good for INCY this year. After that comes January Effect (new money) season, and I expect that to be good for INCY too. The Lilly NDA filing may have some effect (hard to predict whether portfolio runners will connect it to INCY). Next unschedulable event likely to be combination results on Opdivo+epac. Since the cube rats have dismissed epac, that's more a risk than an opportunity. Next Q release ought to be received well because there ought to be enough milestones to turn the bottom line black. Serious risk [opportunity?], though: YoY Jakafi earnings comparison can hardly return to +69%, and isn't likely to match +65%; a decline there could become a hook for unfavorable reports [continued drastic growth could change estimates of ultimate market size].
After Feb, we're likely to be in a "Show me the money" environment. Janus-1 will report; it's likely to succeed, but I'd put the probability of that closer to 70% than to 90%. Showy success would mean immediate money while complete failure would at least take Janus-2 and its costs out of the picture. Trying to push my crystal ball farther causes overheating. One thing that doesn't matter much to us financially, but may affect the climate on the board: I expect that S,N oligonucleotide to be entirely redirected to MDSs around April (too many grade 3 AEs to push on against a target with other treatments available)
Spent some time looking at long-term charts (log scale). What we've seen so far is a little worse than the drop 2 years ago (If I remember right, that was prompted by doubts about the ability, both in financial strength and selling talent, of Incyte to introduce Jakafi for PV) or "the bad conference call" (2012? How time flies. The issue then was whether management was in touch with reality at all. In particular, Dr Paul gave a sloppy presentation and the fiction that the dark pipeline was genuinely secret was demolished). Not nearly as bad as the post-Lehman drop (stock lost about 3/4 of its value). The big moves before then were a different company with the same name. The run up from $25 to 65 looks like 2 up phases of about the size of the drop so far. That was driven by movement of Jakafi into routine clinical practice (immediately after the product was introduced, duration of treatment was short. CME spreading the titration protocol that eventually went on the revised label fixed that--the second stage of that rise was the actual label revision and PV approval).
I simply don't see a prospect of a 2008-scale overall event. That was a $40-50 TRILLION freeze-up, with $5-7T gone after the smoke cleared. The energy/heavy construction industries might wind up with a $multi-trillion hole in them, but probably a smaller total, in a larger world economy, and with enormously less confusion about who owes what to whom, when it's payable, and who'll still be solvent by then (The craps table scene in The Big Short tries and fails to capture the frenzy, which is where the $35-45T temporary loss happened).
My broker brought up 1987. To be sure, the feel is similar: a long-ish period of generally dull/bad market behavior followed by a crash, with no apparent trigger. That was worsened by the physical tape still being used by NYSE and by "portfolio insurance," which backfired in a fast market.
Well, perhaps a trace of optimism. With the filing in on bari, and the spectacular p 3 results, I'm calling it a product. The optimism is in the guess at peak sales, which I'm guessing will be enough to send over $1 B a year Incyte's way. With estimated peak sales of Jakafi for existing indications (+ Jakavi royalties) around $2.2 B a year, the share price now gives Incyte an enterprise value about 5x estimated peak sales of existing products. That's what ordinary drug development companies go for...leaving nothing for JAK inhibitors in solid tumors or for epac, to say nothing of the numerous other projects.
You could argue that Incyte has financing needs beyond its ability to generate the money [and I have], but with most of a year's expenses worth of cash on hand, a $35MM milestone coming in soon and a roughly $10MM/quarter bari research participation expense ended, the need for financing isn't imminent. It's likely that publication of the Comfort follow-ups reported at ASH will FINALLY get N.I.C.E. to approve Jakavi for MF, which should result in some milestone payments. And approval of the bari NDA triggers a big milestone...major new financing is unlikely to be needed before the memory of the 3 trading halts has faded (or until the people who lived through it have all moved to different jobs).
Not that the carnage will have to stop, but sellers are starting to sacrifice badly.
I'm not sure I heard even a word from an Incyte participant; all Lilly.
Had anyone heard about plans to try bari against lupus (sounds like a longshot to me) and atopic dermatitis (quite a large basket of stuff; more likely to work than lupus, but little room for high prices or safety risks). before today?
Effectiveness was spectacular. Pretty much, the closer you look the better. Safety is going to be talked about for a while. For both continuity of treatment and objective structure protection reasons, you'd like the combination of MTX with bari to do well, and that is naturally the only place there's a question. And of course, even when there are full publications, the patient-level safety results will be in on-line appendices. Clearly, recent zoster immunization will be suggested for all bari patients; probably annual derm examination too [neither one likely to get a black box]. It looks generally as if the more hydrophilic (relative to Jakafi) nature of bari is giving adequate reduction in marrow effects (the greater energy reported by bari patients compared to Humira ones is very encouraging)
Lilly doesn't expect to market bari in 2016, which might just be FDA relations (NEVER try to light a fire under them), or might reflect a decision that getting the best possible label is more important than reaching market at the earliest date.
Sure enough, there was a Xeljanz question.
Anyway, there is clearly no more "if" about regulatory filings.
1) we don't and can't know the language of the licenses. They may believe that a payment is due and the legalese might be obscure. At the time of the announcement, before the quarter began, there was no public disagreement with the statement that the payment was due. Anyway, there's still a week left in the quarter. I'd say to ask again after the CC, or at least after the JPM conf, but I hope you'll be gone.
2) Incyte doesn't dominate either index. The most believable origin of the truism "They will fluctuate" is that it was JD Rockefeller's answer to a question from William Poor about how the companies within the Standard Oil trust would do relative to each other. Same answer is even truer for components of an index.
Now go away.
Oral presentation 824 today at 4:45 PM. Combination of ruxoltinib with pegylated interferon alpha 2 produced CR in 4 of 10 MF patients. The Minnesnowtan has gotten a lot of criticism for his venom against interferon, and of course he hates ruxolitinib worse. If he survives the stroke, we can anticipate that he'll call for a meeting to redefine CR in myelofibrosis.
More realistically, this combination is unlikely to sweep the world immediately. The dosage form of interferon used in this Danish study isn't sold in the US (I don't know whether it could be), and the AE profile in the demo group (10 MF patients + 20 PV patients, all of whom had unsatisfactory response to interferon alone) was worse than you'd like for a first-line treatment (but not as bad as in the Mayo 33)
Lilly isn't exactly a pushover. The anti-TNFs have had a great run (and I made a lot of money in Immunex, which was bought by Amgen to get Enbrel). But they can't be given orally, they lose effectiveness (probably mostly by raising antibodies), they're inherently expensive and they have some jackpot side effects. When I say $1B annually to Incyte, that's Lilly getting just an equal dollar share as one of the big anti-TNFs. Really, I expect anti-TNFs to be historical curiosities in a few years. Bari may not be the last word, but it's a move in the right direction. More selective in action, oral, no sign of losing effectiveness, no sign of anything that might earn a black box. And cheap to make. Manufacturing cost comparable to MTX. I'd hate to see a race to the bottom, but bari would be wildly profitable at a price biosimilars couldn't approach.
And of course Lilly, who know a thing or two about diabetes, are giving bari a shot against diabetic nephropathy. Most expensive single syndrome in the US, and absolutely no specific preventive.
You got a financial interest here? Tell us about it.
I've tried written abuse. I'm not bad at it, but I'm SO much better at logical arguments that I hardly bother anymore. I don't mind the court jester reference, since traditionally the jester was the brightest guy around. On the other hand, nobody wants to see me swimming naked.
I'm getting tired of geroniacs here.
1) Easily read from the on-line appendix to the Tefferi NEJM paper: in a nominally 9-month study on 33 subjects, there were 48 grade 3-and worse adverse events.
2) Anything resembling that level of SAEs would mean that Imetelstat will never be used when there is an alterative.
3) Almost by definition, MF patients eligible for the J&J study are sick.
4) Some of those sick subjects are going to die (needn't be from drug effects)
5) Dead subjects, from whatever cause, are a problem for J&J
6) Imetelstat is very promising for MDSs, for which it would face little competition
7) Many potential trial subjects for MDS treatment aren't sick
8) Life will be a lot easier for J&J if they suspend the MF study at the earliest plausible opportunity
9) Half of the Jakafi market is PV, in which a major side effect from MF is a benefit
10) Pretty soon, Incyte will have just as much business unrelated to MPNs as related
11) So make like a shepherd and get the flock out of here.
I'm trying to be gently helpful, but I fear it will end badly.
You're getting breathless and shallow again here. I have some ADHD too, but yours shows more.
The real problem is with how weird it is to say that there's less competition in the RA field. You have a zoo full of NSAIDS and conventional DMARDs, and at the top of the heap Enbrel, Humira and I think it's up to 3 other anti-TNF drugs. Not to mention (I wish we could avoid mentioning it) Xeljanz.
And that brings up "more money" than what? Certainly, more money than MPNs, but a really general cancer drug can take the lead in total drug sales (Avastin has had it)(Jakafi for cancer cachexia is the unstated but unconcealed goal of the Janus-es). If it's "all" about the R/A prospect, what about epacadostat (which we've just seen gets a lot of attention; use against NSCLC could certainly mean a lot of money--and Incyte owns it 100% rather than the "high 20s%" for bari) or the possible use of bari to head off diabetic nephropathy (call it a single indication, break dementia and heart disease into multiple indications, and you have the costliest medical condition, with NO existing competition)?
I may have said it before: sometimes I decide something I've written just sounds wrong, delete it and start over. You might gain from doing something similar.
There was just a "Palliative care in oncology" symposium with a session on anorexia and cachexia. In other words, they discussed the problem that lots of cancer patients lose weight, some while not eating and some despite eating. There are a few relatively ineffective treatments. The problem is extremely distressing to family, but apparently less so to the patients themselves.
Anyway, this is a good time for awareness, because ruxo produced weight gain in terminal pancreatic cancer patients in the Recap study. Janus 1, remember, reports in April.
Tefferi pulled those patients out of his site in the phase 2 trial for reasons we can't know. Subsequently, phase 3 trials and follow ups have shown that those claimed results were unrepresentative, at best. One of the patients he pulled from the study nearly died from sudden return of MF after withdrawal of effective therapy, a result he lyingly described in print as a "novel withdrawal syndrome." (I'd use a milder description if The Great Hematologic Oncologist had suggested in any way in his paper that return of MF was involved. And it isn't jacosa saying that it was return of MF, that description was approved by FDA)
In an oral presentation this evening, Dr Nadja Jaekel (speaking for her group) reported that among a group of patients assigned to either hematopoietic stem cell transplant [read: curative treatment] or ruxolitinib treatment exclusively on the basis of donor availability (accidentally turned out to be comparable numbers--50 transplant, 58 ruxo), the ruxolitinib patients did not do significantly worse than the transplant patients in any way (six year study duration, 5 year coverage for inclusion; in general, patients were on study about 1.5 years before donor search was judged futile). The groups were generally well matched, except that the ruxo group were a bit older and started with bigger spleens (both negative prognostic indicators).
The phrase "tantamount to a cure" has been thrown around before...
Nice find. I haven't seen reports by Colin Bristow before, although I seem to remember Sara Blum.
The analysis of the RA opportunity is much too cautious. Baricitinib tests out superior to the best anti-TNF (and of course to MTX), is administered orally (in contrast to the anti-TNFs), is projected to cost somewhat less than the anti-TNFs and they project 3.5% market penetration? "Pull the other one, it has a bell on it." Yeah, yeah: they have market research and I only have a few anecdotes. RA patients will push back HARD to get pills vs shots, and as for infusions? Not bludy likely. Incyte may not be as good at playing insurance companies as the big boys, but Lilly IS a big boy.
The stated belief that JAK-1 exclusive drugs will be superior to JAK 1/2 bari is probably wrong. Yeah, the phase 2 results look that way, and I'm not going to tear up the trial designs at this stage, but given the proposed mechanisms, JAK-2 inhibition is helpful, especially for protection of joint structure (something that wouldn't show at all in a phase 2--and without structure protection, good luck with regulators).
It was interesting to see that rheumatologists like to rely on indices of disease activity. newer measures of RA activity (I'm most aware of Myriad's Vectra-DA, but there's at least one other) actually correlate with disease progression, and correlate little with traditional measures of RA activity. I think Rheumatology practice is going to be changing fairly fast.
The aside that Incyte hasn't opted in on psoriasis development is ne to me. From the context, I can't tell if that non-participation extends to the other use extensions. We may hear at the JPM conference.
Usually I wouldn't start a trivial topic like this. But here, I'm emulating T and V--I don't like that subject line, so I'll try to get it off the first page.
I think I'm the only jacosa on Yahoo. Try searching that on all boards. You'll find a lot of activity in a lot of places. The style is recognizable. I'm rather happy with my exchanges on the Myriad board in the past year with a poster whose identity contains 'herbst' [she(?) uses several similar identities for a reason I don't know].
That "comparable" is probably because of the comparisons vs Humira+MTX. There are some clues from the ASH presentations on how to reduce AEs from JAK inhibitor therapy (biggest is that steroids add more to infection risk than to effectiveness). I'm sure Lilly plans some supplementary studies.
Predicting an adoption timeline is silly. so I'll try. My scenario is a label that permits first use if there are reasons to expect MTX to be a poor choice, and use after one failed TNF inhibitor; pricing a little below the anti-TNFs. I expect that a noticeable fraction (1/5 - 1/3) of those who have just failed their first anti-TNF will try bari, and maybe 40% of those who've failed a second one. That should give a faster initial sell-in than Jakafi had for MF. The foot of the adoption curve may be long-ish, but I think soozanie's 18 months is an upper bound--the secret here is that JAK-1 inhibition just seems to make people feel good. I don't expect the steep part of uptake to reach the 65% YoY that Jakafi is now showing; maybe 50%, but for a long time (ok, I'm an enthusiast--until as many patients are on bari as on all other advanced DMARDs combined)(there should be a label change somewhere in the middle based on whatever Lilly's fill-in studies show)
There's a misalignment of interests between Lilly and Incyte. Lilly wants the highest peak sales while Incyte wants substantial sales soon. It's very unlikely, but possible, that Lilly could delay NDA filing to seek clinical results supporting a label that permitted first use in any circumstance.
In clinical trial NCT00310895, completed over 2 1/2 years ago with no published results, their candidate did nothing of interest against assorted relapsed solid tumors.
Five years ago, Incyte had patents on a drug candidate called ruxolitinib (we mostly called it '424ib' on this board. Good candidate, worth maybe $800MM. Today, the same patents constitute a monopoly on a marketed drug called Jakafi. Worst bearish value estimate around $7Bln. In keeping with the version of GAAP generally used by big drug companies, that patent portfolio is kept on the books at the legal cost of obtaining the patents--a constant. No earnings hit the reports in response to increased value of the patents.
One year ago Incyte had patents on a drug candidate called 'baricitinib,' in phase 3 trials (none completed). You can see where this is going.
I'll read it, but the 9/3 NEJM article pretty much speaks for itself: adverse events were far out of proportion for a usually-mild disease. The coupling of the lifting of the hold on IM with announcing that no further trials against ET were planned came about as close as FDA ever does to saying that such trials wouldn't be permitted.
Neutropenia in ruxo and Im contexts is an interesting issue. Apparent neutropenia caused by ruxo is due in substantial part to partial activation of neutrophils, which causes them to adhere to blood vessel walls, but does not greatly reduce their ability to respond to invasions (this was a major issue in clinical trials). Neutropenia seen with Im treatment seems to be due only to reduced neutrophil production.
Too close to quarterlies for a full report, but we get something.
Kind of odd. First straight answer I've seen about the low-CRP cohort in the colorectal study--the futility/slaughter analysis is event-driven in each separate cohort (presumably by number of subjects reaching a certain duration of treatment), and there have not been enough events to trigger it. So that part of the study continues.
Ying Huang had been the only analyst explicitly attributing substantial value ($26 a share) to the prospect of ruxolitinib being used to treat solid tumors. So on the basis of this setback, he has dropped his price target from $145 to $87, maintaining a buy recommendation (the best of the present crop of analysts is still covering his a.. rather than being honest).
There are some nasty words for how analysts are looking at the Recap results. I think maybe it'd be better to put the details elsewhere. Let's put in the placeholder that there's no honest justification for assigning a prior probability of success for Janus 1 that is much less than 70%. So all the analysts suddenly assigning zero probability to any use of ruxolitinib in solid tumors are using something other than functioning intelligence.
First, about HH. His accent, while obvious, was toned down for greater clarity. I knew he could do it. He presented a convincing sound of enthusiasm and excitement.
I didn't expect new candidates in this venue; we got two of 'em. With so many early stage candidates, it's hard to get very excited about two more. But public discussion of these maintains the difficulty of assigning a fair value to Incyte and indicates an intention to stay independent.
In the rapid exposition, both alopecia and GVHD were mentioned--both of these are potentially large markets, but not advanced enough to really want questions about them.
The sales growth chart for Jakafi is astounding. And HH pretty much promised that the next segment will maintain the 60+% YoY slope. We'll return to that after the quarterly report.
Comments on the Janus program could have used clarification. HH outright said that the PROGRAM is fully enrolled. He promised results this year. That might mean that Janus 1 has had slow enrollment and he's ignoring Janus 2, or that Janus 2 won't happen however Janus 1 turns out. On the positive extreme, it could mean that he is absolutely certain that Janus 1 will meet the standard set in the SPA. Or a lot of other possibilities. The remarks were early enough and prominent enough to suggest that he wants analysts to watch for developments, so I take that as hopeful.