I sure picked a great weekend to get norovirus (over the illness but still highly contagious); still, it gives me a chance to think about stuff.
In Recap, the patients who entered hospice care all discontinued Ruxo (check me on that). I'm curious about whether they had any choice, and about whether there's a prospect of palliative use of Jakafi going on-label as a result of the Janus trials.
Ruxo alone was not a test treatment in Recap, so continuing it in a hospice setting would have been outside the protocol; Capecitabine is a drug meant to prolong life which does not increase patient comfort, so it would surely be excluded from hospice use. So in a strict sense, continuing Ruxo into hospice should be excluded. But objectively, a meaningful number of subjects on the trial drug experienced weight gain, which is unheard of among terminal PaCa patients, and which in itself contributes to subjective wellbeing in both patients and families. Subjectively, it's not presented in a way that's easy to be sure of, but non-specific constitutional problems MAY have been helped by Ruxo.
One of the secondary outcome measures of Janus 1 is "Safety and tolerability of the treatment regimens assessed by a summary of adverse events and clinical laboratory assessments. [ Time Frame: Baseline through approximately 30 days post treatment discontinuation. Approximately 21 months. ]"
Again, Ruxo alone is not a treatment arm, but the study is large enough to highlight any "never happens" tolerability events. It seems possible, in principle, for Janus 2 to be modified to allow continuation of Ruxo alone into a hospice setting, if the hospice programs agree. That could be enough to put it on-label. Hospice programs could adopt palliative use of Ruxo without a label, but Incyte can't promote it without one.
We seem to be getting fewer characters to a posting.
The long-time ends of those curves are confounded by crossovers in the trial designs, and of course you should study inclusion and exclusion criteria and protocols to be accurate about who is helped by what sort of treatment. But just from those curves one can say that a fairly typical mild-to-intermediate-risk MF patient will live a year longer taking Jakafi than with the control treatments.
Future refinements in what you can say about survival advantage will not have such compelling trial designs behind them. The best we can hope for in medium- and high- risk patients is comparison against matched historical controls. While treatment of indolent and low-risk MF is not on the Jakafi label, we can expect to see studies in these groups, either from Incyte or from independent investigators. These trials may have simultaneous randomized control groups.
Note that for less-rapidly-fatal diseases, a modest visual separation of Kaplan-Meier curves can represent a substantial difference in survival time. On the other hand, when we see results presented concerning pancreatic cancer, large visual separations may represent few days of survival. There are drugs that change the shape of Kaplan-Meier curves (this is often called disease modification) and drugs that shift the curves (often called giving a respite).
We haven't been affected much by it here, but lots of other internet stock discussion areas are in the throes of yet another [you know what company] battle. Basically, with a string of not-bad events, the stock price went up substantially and that appears to have precipitated a bear raid. The people who plague us from time to time are defending the stock price. I wouldn't have noticed, except for some Seeking Alpha articles suggesting shorting Incyte. There are the usual bleats about Jakafi giving only relief of symptoms. I just want to make it clear how dramatic the evidence of a survival benefit of Jakafi is [the magnitude of the effect is probably why the FDA took the extraordinary step of allowing data from a post-hoc trial data analysis on a drug label]
Look at the right of page 8 of the professional package insert (find it online). Those curves show fraction of survivors vs time. There are details about how they're drawn, but with enough subjects and enough time the details become ignorable. What first catches the eye is the vertical separation between the curves, which is unfortunate. That's the difference between %survivors on the treatments compared at a given time; a rather sterile number. More compelling is the horizontal separation of the curves. That compares the time that a given fraction of subjects survive until. At a first glance, the 2/3 survival level is a reasonable starting point. In the upper graph we get a crib: the numbers called out say that 1/3 of controls had died by the 2 year point, but that number of deaths was not yet reached by 3 years in the treatment group. The lower curve shows slightly better experience for the control group, but very comparable experience for the treatment group. Less
Geron fanatics are good for something. One of them alerted me to a study out of Dr Verstovsek's lab recently published in "Blood," showing that the relatively small number of MF patients with 3 or more of the mutations commonly associated with MF do substantially less well on Jakafi than those with fewer mutations [Of course he was trying to say that it proved Jakafi is a lousy drug]. It isn't completely clear from the article, but the test looks comparable in complexity to some in use as companion diagnostics. It's also unclear whether this was a new purpose-designed study or a more detailed analysis of earlier results. I'm not including the link because I had to register to see the article.
Obvious significance is that there's a real hope of this turning into a way to identify patients who might need extra attention if they are given Jakafi. Slightly less obviously, this may become part of the case for putting mild MF onto the Jakafi label.
Look up the news story. Company name is Immunovaccine. Phase 1 trial. Unusual case: usually Incyte wants maximum publicity but the collaborator wants secrecy. Immunovaccine wants SOME publicity.
Tricky. Any dividend and any proceeds of liquidation must be split with the same amount per share for both classes. The management advisory fee for the last 2-3 years of its existence looked like an end run around the dividend rule. The change in corporate bylaws by reverse merger shows how the whole thing could be defeated. But shafting the owners completely without triggering major legal action is not trivially easy.
When does that phase 2 read out? And normally, even for an orphan indication, a phase 3 is required for approval. Furthermore, Incyte is already permitted to include a lengthened survival claim on the drug label; no matter how good Imetelstat might turn out to be, it will not launch with survival on its label (no previously treated patient can be counted because the present study is the first in MF with the kind of statistical safeguards FDA requires).
The market has a short and a long side, and neither is immoral. (As long as the law allows, I'm happy to be making money charging what the market will bear for a vital drug). Shorts tend to be smarter and more interesting than longs, but they go broke pretty often.
I just found out what the proposed trial looks like. Combination of a biological that is targeted against a protein that helps cells resist an order to kill themselves from immune cells, an old-line DNA damaging drug and the IDO inhibitor. Pretty typical for this year's immunotherapy trials.
His important holding is Class B common shares. No [dividend] preference over Class A. Any spectacularly anti-owner action would prompt lawsuits. Directors are personally liable, and if they act perversely to their fiduciary duties, I don't think their insurance covers it.
I have no history with you, so I'm not interested. I'll give you *herbst*'s advice to me re EZPW. If it's broken and you know it, get out. (And while EZ has run into severe business problems, and still hasn't done anything owner-friendly, they HAVE abandoned their most owner-hostile practice--paying the dictator for investment banking services.)
As long as you're talking your own book and not somebody else's I'm talking mine. And EZ could STILL turn the stock around with no effort at all by making some owner-friendly gestures. Unlike my REAL stinkers of the past.
My average cost basis for MYGN is a shade under $35, with some $35 Jan puts short too (I've taken out a couple bucks with options, but we'll ignore that; anyway, this is crunch time so I do no more options stuff until August). So say I'm even, today. Unless you say otherwise, I'll assume that you're short around $30 (GS is big and tough and nasty, but anyone I'd choose to talk to is smarter than them).
I'm on record predicting a big August up move, but please give me a quarter leeway as long as there's no drop. When do you want to match results? I'd suggest January expiration, but that's sort of cheating. But not forever. (I was short Gaylord for most of a year before admitting that they had fixed their problems. I was short AIV longer than that, and profited in the end, but the annoyance wasn't worth it. I DO want out of Myriad myself, because INCY has some hammer blows coming up)
Incyte just received a ruling allowing it to keep exhibit 10.1 from the April 30 form 10Q confidential. I'm tired. Anyone care to figure out what the general subject of exhibit 10.1 would be?
I was looking at a lot of old Yahoo message board postings over the weekend, going back a long time. I remarked beckyherbstinvestor, rebeccaherbstinvestor and rebeccaherbstinvestorfan. My login has remained constant. Usually, the logins of that group have been more sympathetic to my views than you are now. And usually, we were on the side that was eventually closer to right.
The value of Myriad is in trade secrets and in corporate culture, not in patents. The threat from lawsuits was always endless distraction, not loss of monopolies. This is not a safe short.
One of the symptoms Jakafi controls is death. Avoiding death is generally regarded as disease-modifying. See page 8 of the Jakafi professional package insert.
Patients continue on Jakafi for a long time.
Jim Daly was brought in to deal with issues around "The Bad Conference Call." Basically, once HH settled in he became a fifth wheel.
It DOES seem early to be setting up an international structure, but it could be needed VERY quickly if one of the major combination trials was to show dramatic results (and we're in the season when those come into play). In a bigger view, Incyte is rapidly becoming more complicated, and at this stage, you can't have too many spots for evaluating managers. There's a "too many chiefs" risk of course, but for the moment the corporate culture ought to forestall that.
Actually, for 3 years hence I find those numbers conservative. Partly, it's because I regard the Bari estimate as low, and partly it's because by then I'd attribute some value to candidates not presently in the clinic. The MPN numbers seem to imply great price restraint on Jakafi (which I advocate). I'm a little cautious about the IDO inhibitor number; immunotherapies have never looked as good as they do now, but they HAVE looked good before and failed anyway. But if any immunotherapy pans out, it will at least sometimes include IDO inhibition.
I don't see US interest rates rising, at least under Obama and Yellen, until there has been an actual print of US core inflation over 2.2% (depending on oil, bird flu and Western rainfall, that could easily be 4% nominal). Well, maybe the "inside baseball" increase in interest paid by the Fed on excess reserves to 0.5%, just to blunt criticism, between Sept and Jan, but nothing "real." There are good economic reasons to be cautious about raising interest rates, and the team in place aren't hard money fundamentalists.
As soon as somebody has a reason for $4+ jump in one hour, please post something.
Almost by reflex, I checked Merck. Nothing in the news there, either, although recent commentary highlighted their immunotherapy program.