I mis-spoke about 5-year survival. The control groups in those trials generally crossed over to ruxolitinib. Survival is more than twice what was observed for patients receiving treatment matching the controls as of the time of the studies.
He mentioned it in the SA article. He considers it a long-term threat to the business of Jakafi for MF.
As for what actually happened in the Mayo Clinic demonstration series, you should read the full report in the Sept 3, 2015 issue of The New England Journal of Medicine, preferably along with the on-line appendix. (Many hospitals have back issues of NEJM available; I went to a university library to get the appendix. Tefferi ought to send you an offprint if you contact him.). A drug with the properties shown in the NEJM article (7 patients of 33 responded at all; there were more adverse events of grade 3 and 4 than total patients treated) would never be tried until after Jakafi had been tried and failed (that is, in fact, the subject population for the Janssen study).
There have been 5-year follow-ups published recently on the 2 phase 3 clinical trials of ruxolitinib as treatment for MF. They're quite favorable; in particular, patients with intermediate-2 MF at time of enrollment have median survival more than twice as long as with placebo or prior best available treatment.
There was an attempt in the NJM paper to confirm the proposed (anti-telomerase) mode of action of the drug. The Editors (M. Armanios and CW Greider) commented that it left other possibilities for mode of action open. What works, works, however it works, but in predicting generality and duration of activity, the mode of action is guidance. Anti-telomerase activity leads to more favorable predictions than most other possibilities.
Couple more things: unenthusiastic reaction is likely because while the HRD-positive patients did a lot better than the HRD-negative patients, the all-comers response was pretty good. The full dataset contains stuff bearing on that. Myriad doesn't own the data so they can't comment much. For a few reasons, standard of care is likely to include the CD, even if the drug is approvable for all.
Explaining to a lay audience the value of hereditary cancer testing in patients with known cancer remains difficult.
Very positive call. It may be possible to get around Myriad's patents, but definitely not easy (and they DO appear to be good patents).
It isn't clear yet whether CD will be required by FDA, but payers will be a lot faster to reimburse the drug with CD.
Adoption of a CD has more drug-like dynamics than test-like dynamics--the transition from the slow initial phase to the rapid-growth mid phase happens earlier.
There are apparently about half a dozen other indications being looked at with anticipated topline (or better) in the next 12 months (of 22 total ongoing studies).
A fairly full presentation on this study is anticipated at ESMO (in October). Since there are likely to be meetings among the companies and FDA in the interim, the presentation may well include the specific analyses that FDA was most interested in.
There was a question about the delay in implementing the regulations to make reimbursement levels for devices and tests more predictable. Myriad doesn't expect major impact because the reference price determination phase is not being delayed, and much pricing is under contracts extending past the new implementation target.
Niraparib looks like a better drug than Lynparza, so there's some halo effect there. And it sounds so much better to say that HRD testing identifies 50% more patients who might benefit compared to previous CDs, compared to the story told with platinum drugs and Lynparza (we can spare patients these drugs would be futile for from the expense and side effects). Same thing of course, but better positioning.
We learn something real on Thursday, but the drug looks approvable and a CD will probably be on the label. Frankly, the time to actual money is probably over a year, so I don't expect a huge effect soon.
This year it's still mostly Vectra and Prolaris; be REAL nice to see 17% QoQ in both o them in the next CC.
That smarted. But looking back, I see Incyte has been making higher highs and higher lows for the last 4 months. That sort of thing tends to be a bit self-reinforcing. Whatever. We're in for 4 months of politics dominating everything. The only thing I can see in that with more than a brief effect would be a clear sign that Elizabeth Warren will or will not be errr "messing with" the drug industry. If she's VP or Treasury Secretary she'll be distracted. If she's Commerce Secretary, she might easily get involved. I don't think she'd take HHS. And if she's still in the Senate, all bets are off. (If Trump wins, I put most of my investable funds into canned food, but that's just me).
Motley Fool had something about Agenus yesterday. Piece projected a need for [presumably dilutive] financing around EoY. Curiously, that's also estimated timing for bari approval milestone payments from Lilly to Incyte. If ongoing trials look good, Incyte might buy more. The theory has always been that for development of biologic / small molecule drug pairs, any on-target biologic is good in the early stages. And contrariwise, for a developmental biologic, early stage trials as part of a combo can pay for what would otherwise be substantial nuisance expenses.
For all the Brexit-related talk about European bureaucracy, EMA may well approve bari a bit before FDA. EMA "showed their work" on Xeljanz, and protection of joint structure was most of the story. Lilly made sure that was well-addressed in trials.
Seems worth bumping on a bad day. Market cap up by a decent fraction of $1 bln. Peak market for ruxo looks higher by maybe $1/2 bln mostly because of GVHD excitement (again, it's not clear whether that has already shown up in sales, which would lower the ultimate market). Case for starting Jakafi in earlier stages of MF has strengthened, but I'm still not counting on it. Bari approval is now within investment time horizons. First p3 on epac has started. A European business organization has been bought relatively inexpensively (but in a way that could be undone in case of a merger). The diabetic nephropathy trial is definitely off, which is a big long-term negative, but almost as big a short-term positive. Capmatinib and the delta candidate are looking like more than just leads.
ESMO, in October, looks like a real possibility for one of the "other combinations" with epac to report something, so I don't expect anything earlier. Merck, on the other hand, probably wants a journal publication of its combo results to help study recruitment; they may reiterate them at ESMO or wait until SITC.
Net: I'd make the "no air" valuation about $68. Yeah, I have seen a good company (TSRA) sell for less than cash-on-hand (in '08), but buying generally comes in at some reasonable level. Main risk is political.
Graft failure is less frequent but more devastating than GVHD. With the latter becoming more treatable, will SCT be used more, or will fear of the former prevent noticeable changes in practice? [for comparison, I'm strongly "Don't know"]
Would you be wiling to participate here regularly (or at least occasionally)? We can use more intelligent discussion.
I think ruxo is becoming / will become the standard of care for acute GVHD before breakthrough designation can have any effect...has a lot to do with physician personalities. The kinds of oncos who do a lot of SCTs are also fairly active in using available drugs off-label. Short-term / cash, I think the big effect of the designation is the couple $tens of millions it's likely to shave off the expense of getting the label expansion.
I think the risk of transplant failure will be enough to prevent large expansion of the use of SCT soon, but better treatment for GVHD will tilt the choice between autologous and mixed autologous / heterologous SCTs where that choice is a live one. That may be a big deal for myeloma treatment. (A LITTLE anti-host reaction from the foreign-derived marrow helps control the cancer)
It was frustrating when N.I.C.E. gave the narrowest justifiable approval to sale of Jakavi. But with a couple years of limited English sales as a result of that, it partially insulates Incyte from Brexit (and I DO believe Britain is headed for the big exit--Scottish devolution soon, possibly with a less-than-friendly border; Northern Ireland next.) (Welsh participation in The UK has always been something you see if you look one way, and don't see if you look another)
N.I.C.E. is going to have to change substantially to replace the overall approval function of EMA. Probably going to be delays for everything. Unfortunately, bari has very much the profile of a drug most likely to be hurt by the changeover (The case for it is SO strong that EMA might even beat FDA to approval; cost effectiveness likely to get it through N.I.C.E's existing functions quickly--even if it's the first thing English FDA approves, that's likely to be a few months of delay).
I heard a noise from the Midwet about the rarity of GVHD. With about 5000 new cases a year and miserable prognosis, the market is comparable to active MF. Effective treatment could easily double the market size. The present mainstay of GVHD management is steroids. Since ruxo and steroids don't play well together (even alternated), if ruxo is adopted at all, it will likely be used first.
I could be Sleepy, too.
This may save a meaningful amount of money as Incyte brings GVHD on-label for ruxo. I don't know the reimbursement landscape for off-label use, but that ought to improve also. I think a large fraction of the sales possible for this indication are not waiting for the label expansion, though, so The direct benefit of accelerated approval is modest.
The second-order benefits are unpredictable, and may be larger. It'll take at least until the p3 finishes for those to show clearly, because they are likely to involve more cautious oncologists. With improved prognosis for GVHD, more procedures that carry a risk of causing it will be done (particularly mixed autologous / heterologous stem cell transplants--I've said why I'm an avid spectator of myeloma developments, and mixed transplants have a large AVERAGE benefit there, but are limited because the worst case outcome is so bad). Other procedures that have a risk of causing marrow failure will look more attractive as rescue by transplant becomes less desperate.
Interesting MarketWatch article dated 6/20. Looks like drug pricing is going to figure in the Presidential election no matter what, because Trump thinks it can broaden his appeal, and frankly, Hillary is a bit scared to touch it after the reaction to her Turing tweet.
ANYway, there's a suggestion in the article which might get us most of the benefit of UK's N.I.C.E. without the rigidity (which would hurt worse in the US than it does Over There, 'cause we don't have such a tradition of changing laws on-the-fly). A government agency might require cost::effectiveness reviews of selected already-approved [classes of?] drugs. It offers a hope of stopping the present trend for newest drugs to explore unheard-of price territory without intolerably disrupting markets.
Something MUST give. The politics of hepatitis C could get unlimitedly bad (many, maybe most cases were a result of treatment of war wounds but VA can't afford CURATIVE drugs for all; by limiting number of cases cured, an outbreak that could be ended in a year or two can be stretched for decades).
Trump's said to favor allowing re-importation of drugs sold overseas, and to want to free Mdiacare to negotiate drug prices any way they choose. Hillary is thought to favor something much closer to N.I.C.E. (Whose main tool is "You can't sell it for that price. Come back cheaper and we'll reconsider--from the beginning).
Most likely extended report on phase 1/2 of epac + pembo vs multiple tumor types. What we've heard about is longer follow-up on the same subjects from last SITC. I'm guessing a journal publication. "Other" PD-axis drugs + epac probably not until this year SITC.
Trial of a combination of ruxo with low dose interferon could come any time. I don't know the politics here, but on a purely med-sci basis, this would have happened months ago.
Also in the investing time frame, there may be an announcement related to that S,N oligonucleotide. A planned safety/tolerability review has perhaps 1 chance in 3 of causing the dosages being tested to be changed. Change would be announced; no change won't be.
$5 grand in MDT at the right time and I AM retired now (MCI, Immunex .and Intermune helped. Lotus, Intel and HP, not so much.) And incidentally, Medtronic starting around 1999 was a PRIME example of a company where for over a decade, the important things were going right but there were occasional embarrassing headlines and the stock languished.
I expect that this will be just as frustrating a wait as the bari trials, but it's GOING. We can rule out early catastrophic toxicity, so the next news ought to be full enrollment. Be REAL nice to see that by the Feb. CC.
From the quarterly report
» Vectra DA volumes were up 18 percent year-over-year and 11 percent sequentially in the fiscal third-quarter
with approximately 42,500 tests performed.
» Expanded the successful practice integration pilot program to the national phase with our entire rheumatology
sales team in the fiscal-third quarter.
» Signed two private insurance contracts totaling 2 million additional covered lives for Vectra DA.
» Prolaris sample volume was up 90 percent year-over-year and 21 percent sequentially with approximately
4,300 tests ordered.
» Signed multiple additional private insurance contracts bringing our total covered private lives to 28 million.
Meanwhile, the Zack's writer and TMF Ultralong (and a fair number of supposedly more reputable individuals who get paid for their advice) think BRACANalysis is still the bulk of Myriad's business.
The 18% YoY on Vectra represents about 1 Q of active selling, and is consistent with the 11% QoQ. So in August, we can anticipate something over 20% YoY Vectra growth. [severe RA market about 250,000]
The 90% YoY on Prolaris reflects MANY physicians unable to use the test until CMS blessed it. QoQ above 15% in August would be MOST encouraging [Pr CA market about 180,000].
Sometimes you just have to make the money before enough people believe you.
Two more quarters to get a read on how Vectra is REALLY doing. Probably same for Prolaris. Like to see movement toward kit commercialization by Jan. Like to see at least 1 more drug requiring a companion diagnostic.