Not previously discussed here. I only have the abstract online. This stuff is strictly pre-clinical. There seems to be a re-evaluation of the cause of bone marrow fibrosis going on, and this fits in. Old view: defective progenitor cells die; "normal" inflammatory processes cause [permanent] scarring. View gaining interest: abnormal processes in diseased marrow cause structural cells to generate [non-permanent] scar tissue.
Right now I'd guess that this mechanism of action is headed toward trial in combination therapies.
Sometimes I do it to amuse myself. There's an option to report especially serious forms of abuse, and for some reason I picked 'harassment' just lately. Well wadda ya know? It specifically lists repeated posts as a form of harassment. Next time somebody posts 15 times in 10 minutes, we can remember that.
Maybe they'll remove the post with my login in quotes. If not, this pushes it farther down the page.
Not really. I mentioned MDSs in the SA panel, too. A hellish indication. Most of them are too rare to explicitly develop drugs for. IM sort of backed in to an opportunity to address them as a group, and that's presently the best chance. Even if the most common MDSs get cherry-picked by specific treatments, there's still a place for a drug covering all the rest.
I'm being nice, so I won't mention the caveats here. Just don't spend it yet.
I can hardly believe it. Neutral with a $40 target. The issue isn't so much getting clients in as getting short clients out. Still 30 hours to the final Nov short interest number. I expect a further decrease, but still high.
Pardon my cynicism, but with recent volume low enough to make it unlikely that covering is finished, it won't surprise me if the upgrade on a down market day is followed by a very publicized downgrade.
I'm actually hoping IM works for the MDSs. But it's important to recognize that MDS is basket of at least a dozen specific diseases, and IM's special advantage is that it MAY work comparably on most of them. FDA has signaled willingness to accept studies grouping diseases with a common feature. The announced Janssen trial is grouped. The study just presented at ASH was on an individual disease drawn from the MDS basket, so it didn't probe IM's key benefit.
Today's standard of expensive drugs is new. Back in the '70s when I attended lots of colloquia, drug developers talked about resistance to paying a dollar a pill. Later, Viagra made news at $5 a pill. Now, we have half-million-dollar courses of drug treatment...and more. "Sometimes quantity has a quality all its own"
Incyte now has its first practical exercise in making a business of combining its $150-a-pill Jakafi with another company's $700-a-shot interferon (the situation is actually more complicated; on the other hand there may be some flex in interferon pricing). Since this is based on Danish results, Novartis is the natural leader of the effort, but Incyte has an enormously greater need for the combination to enter practice rapidly.
The same sort of exercise will be needed over and over with targeted and checkpoint drugs, which dominate Incyte's mid-stage pipeline (epacadostat being the poster boy).
The obvious solution is a mega-merger (after which each expensive/expensive combination could be offered as a flat-rate package), but the number of combinations involved would pretty much force ALL drug companies into the pot. That general theme seems to be at work in hep-c.
This seems to have been sort-of worked around in HIV drugs, but few of them are viable outside of specific combinations. The motivation to work something out is a lot higher.
SO: any histories of how this sort of thing has worked in the past, not necessarily limited to pharma? Combinations of products where at least one was scarily expensive, and at least one had a use outside the combination. I think of enterprise software, for instance, but I don't know the stories.
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].
I'm trying to figure out exactly what you're talking about. This seems to refer to half of a study begun in 2007 (8 years ago; about twice the median survival time for active MF). If so, and if your numbers were correct, 18 dead would be spectacularly good.
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)
The FACT is that if Imetlstat averages more than 1 adverse event grade 3 or worse per subject [as the Mayo demo series did--again, taken right from the NEJM paper], it won't get far.
Can you tell me how many of the original CRs reported in the original Imetelstat demo series persist after 2 years? I only know for sure that two were lost during the study (one is called out in the caption to a figure as having lost the CR after 13 months; the median duration of CR is given as 18 months, which means that someone lost CR at that time [by definition, a median is present in the data being summarized]). I hear without a reliable source that one has fallen back to active MF. I don't know whether Irish's husband was ever a CR (the patient who withdrew from the demo series for financial reasons is listed as a PR), but he clearly still has MF. No cures here anywhere. But Jakafi has more than 40 5+ year survivors.
Ok, that subject nearly died from sudden return of ACTIVE MF after effective treatment was discontinued.
Whoops--that's a poster presentation, not an oral one.
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...
You don't even talk the talk, buster. Don't pretend you can walk the walk until you've taken on a crowd like I did. And that's DOCTOR Jacosa to you.
I am not an insider at Incyte. I don't know any insider at Incyte, So I don't know why they are selling stock. The same is almost certainly true of you.
What I presume, though, with considerable historical backing, is that there is an informal policy that nobody should have a financial interest in selling the company. They receive extremely generous performance-based compensation.
You have now taken complete leave of your senses. What is a response supposed to mean other than the hope of long-term survival? That is demonstrated for Jakafi, but only hoped for with Imetelstat. In fact, the evidence now suggests that median survival of int-1 and sicker MF patients treated with Jakafi is about 6 years, and there have been refinements added to the method of using Jakafi that certainly reduce adverse events, and ought to lengthen survival.
Yeah, there's some early-stage clinical data on Jakafi in ET; works fine, but the illness is too mild to treat with a risky [and expensive] drug. You CAN'T have read the NEJM paper on treating ET with Imetelstat: among 18 patients, 3 progressed to MF (zero expected on a historical basis) and there were 23 adverse events of grade 3 or higher (including 3 grade 4 neutropenias). All showed signs of liver damage (which was mostly reversible, except for the patient who died). Don't bother calling me a liar; I'm reading this right from the text and tables of the Baerlocher et. al. paper.
I'm afraid portfolio runners, as a group, are stupider than rocks. Few of them will buy Incyte in reaction to an NDA filing by Lilly. Even Lilly won't get the appropriate reaction because too many people confuse the lousy drug Xeljanz with baricitinib. The full benefit of the RA drug on the stock price is going to need to await actual sales, if not actual payments from the participation.
Lilly is making noises that suggest they are going to seek the broadest possible label. This is likely to make the approval process slower than otherwise.