As usual, Incyte is playing the "What's it worth?" game. Nobody wants to make a bid, only to have it topped by someone else. So there's always enough deep pipeline showing to generate a huge uncertainty. There's a new issue, too. It sure looks like epac is going to boost many cancer immunotherapies. It will be better for Incyte over the next few years if epac is available to all on a uniform basis (compare IMAX big screen or Dolby sound).
Basically, Incyte won't be for sale until the founders have made their point (business is no harder than science) and a drug has been taken from idea to stand-alone introduction. And if the quality of the last round of revealed drug candidates is any indication of overall pipeline quality, it won't be for sale at a small drug company price even then.
That said, if bari's label stays clean after a year in general use, and if heaven help us a couple phase 2s for bari in diabetic nephropathy look good, Incyte would look like a bag on Lilly's side pretty much no matter what else happened.
I'm not sure MoA is a BIG issue with FDA, but it's an issue. I keep returning to Intermune as a comparison to stuff: the MoA of their drug pirfenidone was never fully tied down, but it worked and it was eventually approved. However, they got notably few breaks along the way. Regarding patent status, if the activity of Im is unrelated to the sequence, but only to length and backbone chemistry, there may be intellectual property around that needs to be licensed, or that another party could license to make a competing drug. Even if the telomere ablation mechanism is entirely absent, there are some other possibilities that Janssen could entirely control.
Very surprising. Like, did you know that only patients with the JAK-2 gain-of-function mutation responded to Imetelstat in the Mayo study? Odd. Based on that, the observations that response seemed unrelated to starting telomere length, that cancer cells from patients had the same telomere length at the end of the study as they had before treatment and that other cancers with high telomerase activity don't respond to Im, the accompanying editorial cast great doubt on whether the straightforward telomere reduction mechanism is at work. Apparently there's some work suggesting that compounds generally similar to Im have funny interactions with cell surface receptors. If that's the mechanism of action, Geron/Janssen's patent position is less clear.
In the Mayo study, many patients dropped out by 9 months, both because of side effects and non-response (and one because of cost). Apparently, one of the CR patients relapsed during maintenance treatment, which puts the "virtual cure" canard to rest. There were moderate elevations of liver enzymes and moderate jaundice seen in the Mayo study. Reversed on dose adjustment or no, that's a Hy's Law signal and pretty much rules out extras-rapid FDA approval For Geroniacs: of COURSE you can get permission to continue studies after a Hy's law signal is seen, but "Forgive and Remember."
Less interesting: in the ET study, 3 of 11 patients developed MF. That's relatively a lot, but the total numbers are low.
Interesting: Tefferi actually wrote the MF paper, while staffers from Janssen did the final draft of the ET one.
A lot was reserved for the on-line appendices, which I'll have to travel to see. We still don't know whether Tefferi gave Im to some other patients before he started counting to 33.
Read it. Nice work. If the whole drug pricing mess comes into the open, this will too, but it's the least spectacular piece. New drugs coming out at astronomical prices make for headlines. Old drugs having prices jacked up enormously just because new owners can do it make for good body text. There are a lot of dollars in pricy drugs having two 8% price hikes a year, but not the news "flash" of the other two practices. Incyte has been doing it, and paradoxically is more likely to continue beause of the article (see, to get maximum total revenue from MF + PV you'd like the relative price of Jakafi in the drug universe to drift down some--to take fewer price boosts. But if it's likely to be an advantage in the future to be SEEN skipping price boosts, it's plausible to take them now.)
So you know that myelosuppression, including reduced platelet count, is an on-target (JAK-2 mediated)effect. That's why I'm reluctant to believe that a JAK 1/2 drug is going to spare counts at constant clinical effect. Which in turn is why you need the head-to-head results to conclude that something dramatic is going on.
This application is a sort of a "horse designed by a committee." They COULD probably get early approval with a very limited label; what they seem to be trying to do is start the process in hope of adding more data in the middle to get a broader label in an intermediate amount of time. That's pretty much exactly what Lilly is avoiding trying to do with the 4 phase 3s on baricitinib. FDA simply doesn't have much experience with changing an application in the middle, so I'm not going to predict speed.
The other objections to the Motley Fool article stand.
They'll file for a "rolling review." which means an early start, but they need some readout from the ongoing trials before anything real happens. My take on why they are doing this is that on present evidence Jakafi has a superior profile on minor-to-moderate AEs, which would leave them with only the "already failed Jakafi" market, a significant fraction of whom won't respond to ANY JAK inhibitor). So they want an improved label, and to get that they nee the head-to-head results. So maybe you start a 6-month accelerated review clock in 4 months, but the need to include data from the head-to-head will probably add a couple months. I could believe 12 months to market, but no lower.
Clearly, a drug addressing the "Already failed Jakafi" segment doesn't hurt Incyte.
But what does the article gloss over? A $50MM+ annual R&D expense that goes away by contract at YE. Janus 1 that reports Jan/Feb and under SPA puts pancreatic cancer on the Jakafi label if it succeeds (I'm not starry-eyed, but a 60% chance of a market over twice as big as all MPNs). The whole baricitinib/epacadostat thing, which potentially dwarfs Jakafi (earliest cash mebbe 15 months).
And then there's the snide treatment of the converts, as if the potential dilution was well over 100%. It's about 50%, and we've seen Incte handle maturing conerts [well] before.
So yeah, hatchet job.
Here's the headline: Could CTI BioPharma's FDA Shortcut Spell Trouble for Incyte? Three points: Pacritinib may be able to reach market "sooner than expected" (do your own guessing, but I'd put the shortest possible at 14 months) with a label specifically for MF patients with low platelet counts; Pacritinib may actually be slightly superior to Jakafi; Incyte has a lot of debt. Sub-point: investors may be put off as GAAP bottom line goes back to red. Article acknowledges that the debt is all in converts, but exaggerates the impact of conversion (I make that about 50% dilution, but in the past Incyte has negotiated partial conversion/partial payback). Article points out the heavy R&D expense, but doesn't try to estimate how much of it is specific to Baricitinib for RA (which ends, by contract, with the year). Article mentions PV and its importance, but doesn't go on from that to downgrade the threat of a limited pacritinib approval.
Basically, a hatchet piece. Assume the competitor is perfect and that it does maximum damage. Minimize importance of un-threatened business prospects. And there's no place for comments.
FDA has approved a combination of these two extraordinarily expensive drugs as a treatment for melanoma (recall that we have recently seen that epac boosts the effectiveness of Yervoy). The combination seems effective enough to justify the price. Because both drugs are sold by Bristol-Myers Squibb, there is a possibility that there may be a combination price.
These drugs are expensive in substantial part because they are expensive to manufacture. It's possible that the R&D cost of Yervoy may have been recovered already, but Opdivo is new enough that sales are still paying for its development. In a real sense, this is the opposite end from Turing and Valeant, but again, it is forcing drug pricing into the news and into politics. Melanoma is relatively common, and a substantial fraction of it merits third-line treatment (about 10,000 prevalence in US). Strictly as a guess, the new combination might add an easily-manageable $2bln to the total US drug bill...but that is going to attract attention.
Good for Incyte: when the news is about half-million-dollar drugs, sub-hundred-thousand dollar ones shouldn't get much press.
I think epac is more on people's minds now. It's fashionable. Bari doesn't hurt, but even the people who guide the portfolio runners are blinded to it by Xeljanz. And of course the index change has to be worth most of a point.
Don't go risking margin calls again. I've got the shirt and souvenir sunglasses too. There you are fortified to wait out this temporary setback and BAM, you have to put up cash NOW. Sooner or later it breaks the whole position (Ask #$%$ Fuld). I MAY clean out my fixed-income and international allocations to get more INCY if I'm REALLY happy after ACR.
Y e e ss. We're going to have to wait until the ACR meeting to see the details on safety, but the topline looked as clean as these things get. Frankly, if you look at what's already out, practical non-inferiority to Humira looks already demonstrated. You could have a statistically significant but small miss on ACR 70 and still get a huge market on the advantage of a daily pill over a shot every other week (and Humira is the easiest-to-administer of the biologics). Also, there are no catastrophic AEs on bari's account So Far.
The big obstacle to making money is Xeljanz. First, it has created a mindset that JAK inhibitors are generally inferior RA drugs--basically, something for use when lesser DMARDs aren't enough, but no anti-TNF works. And it creates a pricing problem: you don't really want to charge less for bari than for Xeljanz, but Xeljanz is up there with the biologics, which is fine for a low-usage drug, but will predictably become a political problem if the drug comes to dominate the moderate-to-severe RA landscape (I'm sure Lilly will enjoy solving that one). To some extent, the 4 phase 3s address both problems: a lot of the advantages that you'd usually only be able to hint at will be right on the label, and the unusually extensive clinical trial program clearly has to be paid for.
And of course, bari hasn't failed yet against diabetic nephropathy. Much too far off to affect stock price today, but put it into your bull case along with Jakafi and '110 for cancer cachexia, and you get infinity. (And every offensive play in football is diagrammed to produce a touchdown)
Ok, you know that I'm a Leftist (an old 1969-s Ripon Society Republican--I have differences with Sanders, but generally the same part of the continuum. Sen Clifford Case was my man.). The Twerp raised the price of a moderately useful old drug more than 60-fold AND took questionable measures to keep others from entering the market. It got picked up in the NY times. From Bloomberg: "Price gouging like this in the specialty drug market is outrageous," Clinton tweeted at 10:56 a.m. "Tomorrow I’ll lay out a plan to take it on." First: the market reaction was to a fantasy of what she had said or might have meant, and even if she had said "We must nationalize the pharmaceutical companies," she absolutely won't be President during the next 16 months, which makes that a pretty remote threat. Second, she was absolutely right. We want to rid the industry of guys like The Twerp (there's an interview online. I wanted to drive pencils into his eyes). It's one thing to say "We charge high prices to support ongoing improvements in our products." It's very different to charge high prices just because you can. It's one thing to say "We own this market because we have patents and another to say "We own this market because we can stop others from following the mandated procedure to enter it" (until the courts finally say that your legal grounds for preventing competition don't hold).
As I keep saying, portfolio runners occupy space and have weight, but they don't need to meet many other qualifications.
The point is that at one time the other end of that clause was clinical use. That may just reflect a former commercialization roadmap for epac that envisioned early introduction as a standalone agent. Dr Paul used to be gaga over the candidate (may still be) and HH may be waiting for a better spot. But it may also reflect clinical results that don't measure up to "That's never come CLOSE to happening before" pre-clinical results.
What you are describing is a "corner." I think I put up a topic looking at a few historical ones sometime in the past year. They don't generally go to their logical conclusion, but unless there was fraud involved, the owners get a nice return, public owners included. The shorts can probably get out with a loss of less than 2 times their initial sale (median price about 80. I would expect realistically a lot less, maybe mid 50s), which is well within the means of the sorts who do these things.
My first impression is that this will be big Some Day, but don't expect too much short-term. The language about "could support registration studies" suggests that phase 2-s aren't generating miraculous results (but Merck would hardly have filed patents if they weren't generating good results).
Whatever it is, republication of old news without a date attached has done nobody any favors...except [putting on foil hat and actually cackling] if a big player was going to put it to the shorts, this would let him get the first 100,000 or so shares cheap.
Second-hand and speculative, but from a good source:
According to the BoA/ML report in response to the release of abstracts for ACR 2015, a flash topline on the 4th phase 3 is likely to come out during the meeting. This is The Big One. Meeting runs Nov 6-11. Your scorecard: substantial protection of joint structure (modified Total Sharp Score) is 100% expected; failure there would be a killer (I guess it could still be marketed); success makes the drug a blockbuster [no pressure, right?]. Non-inferiority to Humira makes the drug a super-blockbuster. I won't think about superiority to Humira yet, partly because I don't know what comes after super-blockbuster. I guess the obvious consequence of superiority to Humira would be approval a couple months earlier than otherwise.