Nothing looks out of the ordinary. Many subjects given single dose. Enough delay so they could have done pharmacology & metabolism, then a cohort of 6 given multiple doses...and catastrophe. It that's rushing things, then everyone rushes things. It may come out that the interval was adequate for pharmacology and metabolism but that they were done inadequately, but that's barging ahead of facts.
In the variant of the Hippocratic aphorism that I prefer, "Life is short and the art long, the occasion instant, the experiment perilous, the decision difficult"...but you don't get reelected (or keep your funding) by conceding that.
David Kroll has some speculation in Forbes about what went wrong. He leaves out that according to early reports the people harmed were the first ones to receive multiple doses of the trial drug. So far, there is no obvious "this precaution was left out."
An old one: back when there were 3 implantable pacemaker companies, over a span of a few years, one had a problem with leads breaking. Another had batteries short out and a third had leads that were too stiff and stabbed people. All 3 got slammed for each single-company problem (one exception as I recall).
This is starting out pretty dramatic. I expect a lot of re-examination of rules for first-in-human trials. And yeah, Incyte has a lot of those scheduled.
I too suspect that this may turn out to have been avoidable, but there are known examples of things that could have gone wrong this way simply by bad luck and uniqueness of humans (I believe the blood pressure drug Benicar has a toxic effect only in humans, and only in a small fraction of humans).
6 grade 4 and 5 AEs in a first-in-humans trial of a neurologic drug. It's early enough so there's some hope remaining for improvement in the victims. Preliminary reports are that illnesses developed after several doses, suggesting that the explanation may not be simple. Neurotoxicity of a neuro drug may be on-target or target-related, probably not completely off-target.
Crassly, this is bad for the whole drug industry. At least it's a weekend.
Yeah, the volume is high for non-event times. Still only a patch on the "patent expiration rumor" panic or the SITC panic. But every highly leveraged institutional with over 30% of holdings directly or indirectly oil biz is one hell of a pool size to get margin calls.
We can hope that post-options expiration there'll be a breather; maybe long enough to appreciate that Iran isn't a stair-step.
In the bad old days, options expiration weeks were when I used to get margin calls.
I'm REALLY weak on the oil industry, but I thought most countries now own their within-borders oil reserves, so stock market risk of regional wars is less than it once was (at least so long as supply is abundant) (no company's reserves will get trashed, because the company doesn't own them).
My defense: most of the overall market downdraft seems to be from forced selling. EVERYBODY serious has lots of exposure to the oil biz, while direct exposure to the Chinese economy is less serious, especially in the US. So to a meaningful degree, Incyte is drowning in oil.
There's a lot of public concern that return of Iranian oil to world markets may drive prices lower. I throw this up for discussion: Iranian oil has never left world markets. It has just needed to be disguised. So lifting sanctions won't bring a stair-step in supply.
The clinicaltrials entry has changed from "recruiting" to "active, not recruiting." Actual enrollment is 318 vs 310 anticipated. The completion date remains April. The Janus 2 entry was not changed.
With 230 study locations, I attribute the slight over-enrollment to loose coordination. With study completion and AACR so close to each other, some sort of flash result may appear at the meeting. It is legitimate, for example, to present a version of the midway futility/slaughter analysis immediately after the full study ends (in the nature of things, the study wouldn't have gone to completion if the midway analysis was very dramatic either way regarding the primary endpoint). As a reminder, because it's been so long since RECAP reported, the rules here are that the study must satisfy on the primary (overall survival) outcome measure, but marketability of the drug [combination] depends on the "safety and tolerability" outcome. The study would not have been halted for dramatic over or under performance on S&T.
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.
And a comment about the tweak. Incyte may be trusting the Novartis-aided investigators to do everything worth doing to show the value of ruxo in GVHD. The indication is desperate enough so good evidence will generate plenty of use even off-label. Meanwhile, Incyte has already stated that the first principle of choosing what JAK inhibitor to try against a given condition is to prefer JAK-1 selective drugs against conditions that include marrow suppression. Check! That's in addition to '110 being fully owned, so Novartis don't own XUS rights.
I'm sure you expected me to tell you to read the Imetelstat articles in the sept 3, 2015 issue of NEJM to disabuse yourself of that fantasy.
I thought HH's presentation was the better one. De gustibus, we can disputandum forever. Both were trying to stuff 10 pounds of it into a 5 pound bag.
It was explicitly stated that the NDA filing for bari will be this year. One of the last tables listed FDA approval of the bari application as expected this year, but Lechleiter was skimming wildly by that stage of the presentation and he didn't read that box. Presuming that they expect a "normal" 9 months to approval, that implies a Q1 filing.
Now there's a thumbs down. I feel better. That patent rumor gets no explicit acknowledgements from anyone. I don't think there's even been a clear statement of what it might have referred to.
The BoA/ML guy groups GVHD among "other," so he wouldn't call anything out. Novartis kicked in on the ruxo vs GVHD studies, so they may drag this ahead.
Bari participation payments to Incyte will get up to at least $1 bln a year; with the top possibility as high as $5B (recent informed guesses run around $2B). So that's generally a realistic price, but lacking optimism. After listening to the Lilly JPM presentation, I don't think they'd pay up. Frankly, I don't think Lilly would have made the partnership with Incyte if given a do-over. So Gilead would probably have a choice of keeping the asset or selling at a sacrifice. There's a catch here: Lilly cares A LOT about diabetic nephropathy, and to the extent bari might have chances of staving that off, Lilly'd want to keep the part they don't own now in friendly hands.
Roadmaps and long-term plans with catchy names seem to be the current fad in businesses that I look at (I suspect that these are being peddled by McKinsey and Company--most one size fits none business fads of the last couple decades have started there or at least been spread from there) No roadmap is going to include getting in the faces of Amgen, AbbVie and Janssen on products they care about, with cheap methotrexate lurking in the wings. Leaving the bari franchise [ahem] a drug on the market
Heck, Incyte keeps making excuses for going on with bari, too. Cancer is ever so much more fashionable than RA. It's just that SO many people have RA, they live a long time, and they're willing to pay to keep their mobility.
Listened to the Lilly presentation. Stated that NDA filing for bari is expected this year. Stated that there are longer-term results available on bari that will be presented in a scientific meeting this year. A table showed regulatory action on bari this year, which implies filing in cal Q1, however this line was not read out loud.
Nothing said about bari for non-RA indications.
Classically, the advantage of a chain is that they can move inventory between stores.
There's also the opportunity for faster training of new guys.
Looking for something that could have been taken as a negative. On page 22 of the pdf of slides, there's the note that use of Jakafi in PV is patent protected until at least 2027. Arguably, this might be a response to a survival of the rumor of key ruxolitinib patents expiring last year.
A correction that's a little less bullish: the ASH presentations on JAK inhibitors in GVHD used ruxo, which has the nice attribute of being on the market. The Incyte research program on GVHD uses '110, which is probably 3 years from market for even the earliest indication.
Yep, that's today's report.
In a small concession to the short-term behavior of the stock: the language on expected timing of Janus 1 is again weak, and that is an important point for cash watchers. Epac, for all its potential, is only useful in combination with other expensive drugs; we don't know how that will work.
Ying Huang earns his money simply for keeping all the moving parts straight. He estimates peak sales attributable to phase 3 and marketed products ~$12 billion, which is a nice neighborhood to live in. Less optimistically, about $5 B of that is attributable to epacadostat, the youngest and least certain of the advanced products. The rest: $2B for existing Jakafi indications, $3B for ruxo in solid tumors and $2B for bari. The big number for epac speaks of boozy dinners with Dr Paul. I still think bari will do better than that. And ah, ruxo in solid tumors: any estimate should come with a range--it could still fail completely, but it could also still be a general treatment for cancer cachexia.