From April 08 until July 10 GILD lost an astounding 40% of its value. HIV franchise had matured, concerns about patent expirations became stronger, and it wasn't clear how the company could continue growing. The next 16 months brought just a small and incomplete recovery, then came the Phamasset deal in Nov 11. After initial scepticism about the $11 bln price tag the stock went on a legendary run and gained some 500%.
The timing of Martin handing the CEO job over to Milligan couldn't be any better. I am looking for an end of the uninspiring stock buy backs that have seen PE contract to 10. Stock is down over 30% from June 15. In the face of growing competition and never ending negative publicity about pricing Milligan should have the next transformative deal on the top of his agenda or his tenure will become a failure. Getting this right will likely be a lot harder than it was with Pharmasset.
Prolific posters on this board were deceived. They believed there was double digit % of normal dsytrophin in the Bx4 because they misread the IF information. Company did not say in Oct 2015 presentation that WB suggested 1%. That is objectionable because FDA wanted WB as gold standard for quantitative analysis. Sarepta just showed gels and said there was a dystrophin band in 9/11 patients.
That's what everybody who owns the stock thinks. Or that it should be even higher. PPS shot up from 26 to near 40 when Drisa BDs were published and AdCom was a fiasko. Now that CRL has been given PPS should go north again after terrible Jan biotech hemorrhage so far. But it doesn't. For much of the day BMRN was even trading better. Nobody understands this except those who have been steadfast with their position that n=12 is an automatic rejection. And those who listen to uninformed statements like today's IBD "
Like Kyndrisa, eteplirsen produced ambiguous clinical-trial data, so its approval is highly uncertain." Anything but ambiguous.
This is the same Piper that just before the Drisa AdCom stated that "these drugs appear to have modest (or possibly no) clinical benefit and are not without safety risk". And stated after the AdCom that "Drisapersen approval odds are greater than 65%". This is just more of the same incoherent drivel that can change at any time, from safety risk to clean safety profile, from no benefit to long-term 6MWT benefit. To top it off there is the expectation of FDA criticism and contentious panel discussion of lack of Phase III placebo-controlled trial. How ignorant are these people??
Martin's desire has always been to position Gilead as a fast growing Nasdaq traded biotech as opposed to a dividend paying NYSE traded big pharma. This was supposed to result in higher multiples. It worked during the early years but sadly today's multiples are lower than those of most big pharmas. The commercial success is tightly linked to smart acquisitions that overwhelmingly have performed splendidly. This success creates an obligation for the conservative and stable management team to continue to do well, and history tells us this will continue to be through BD activity rather than an unexpected burst of inventive genius from their own research. They rather continue to buy back their stock and not panic about a sub 10 PE ratio and feel compelled to run out to buy a business that is anything but a perfect fit. Martin and his inner circle are in total control of this shop, and they are willing to wait. They will not be manipulated into some kind of action by outside financial interests nor will they share or even relinquish their power in a merger.
This is probably the most relevant article on the topic and serves to inform FDA. Three samples are (untreated?) DMD (B, C, E). Results are expressed as % of normal - just as FDA would like it. With IHC, all three samples consistently produce measurable amounts (10.6, 19.8, 9.6 % or normal), and variability of the measurements was considerably high. With WB, B was never even found at all, and E seems to have mostly not been found as well. C was at 11.4%. Variability was much higher than IHC.
IHC seems to over-estimate (of WB seems to under-estimate) dystrophin in samples with low dystrophin. Sarepta's results shown in the Oct. 1 PR seem to confirm this. With IHC they claim a 140% treatment increase over baseline but don't say how baseline or treatment compares to normal. With WB they just state that they confirmed dsytrophin presence in 9 of 11 samples.
If you follow mainstream thinking that DMD baseline dystrophin is around 1% of normal, and you take the 140% increase by IHC as a reliable measurement, you end up with 2.4% of normal after 4 years of treatment. Not anywhere near BMD. Question is would FDA consider it adequate together with 6 MWD results to conclude that etep has substantial efficacy.
I think his go to drink is bourbon. Even after a few of those he still understands a lot more about the current status of the dystrophin matter than you and a whole bunch of other people here - some so massively confused and gullible they should be scared for the poor job they have done understanding a central issue in Sarepta's NDA and how it may affect their investment.
Why Prosensa decided to publish this data is beyond me. It looks extremely amateurish and like an attempt to deceive. First, if you cannot measure with accuracy the baseline dystrophin your effort is toast right there even before you measure treatment dystrophin. And as you say, a modest % increase (and probably highly inaccurate) is totally meaningless. Did they really think the reviewers wouldn't notice? No wonder they earned the scorn of Farkas.
Thanks for your response but what you are referencing is fluorescence intensity. That is very different from % dystrophin relative to normal (non DMD) dystrophin. FDA is not so interested in fluorescent fibers because it is a very poor way of knowing how much dystrophin there is. They want to know how much dystrophin is produced after treatment using an appropriate method for measurement: Western Blot.
Like squirrel I likewise am unable to find this information in the Oct. 1, 2015 press release. Send an apology in all CAPTALS if you don't mind.
"YES, Etep produces 10-15% dystrophin -- clearly."
I want to ask you also for the source of this information. Thanks
"when the biopsies were quantified per FDA guidelines by three independent labs, the 4th biopsies showed 11% OR MORE, in all subjects."
I may have missed the dissemination of these results. Would you please point me in the right direction? Thanks.
The number FDA seems most keen on is not % dystrophin positive fibers (or % dystrophin increase over baseline). What FDA is looking for is % dystrophin after treatment relative to non DMD boys. This is what I heard Farkas say. He wants Western Blot analysis for this measurement. Nobody really knows how much of normal is therapeutically relevant but it is safe to say it must be substantially more than 1%. Sarepta only saw a dystrophin band in 9 of 11 patients after treatment, and in 1/9 untreated DMD controls. Goes to show that Western Blot may not be reliable for extremely low amounts of dystrophin and trying to deliver the numbers FDA wants will be difficult. Good news is that Sarepta has an even clearer picture now of the importance of dystrophin and has a good chance to figure out how to impress.
Dr. V. Tan, FDA: "Efficacy results from open label extension studies are difficult to interpret".
I am concerned that this position may lead FDA to conclude that Study 202 results do not strengthen the case for etepllrsen efficacy.
FDA: "Drisapersen is associated with severe and potentially life-threatening adverse effects. The magnitude of the potential for serious harm after approval is unknown. It is likely that adverse reactions not identified to date will occur in the postmarketing setting. I recommend a boxed warning ."
Biomarin: "Drisapersen was generally well tolerated. The majority of AEs were reported as mild to
moderate in intensity. The most clinically significant identified risks associated with treatment were thrombocytopenia, renal abnormalities, and injection site reactions, all of which are considered manageable through close monitoring and risk minimization measures. In the context of treating a universally fatal disorder, drisapersen has an acceptable safety profile.
FDA is not going to be gullible for Biomarin's spin on safety. It's an insult to the intelligence and professional integrity of the agency's reviewers. In the end drisa safety may not even matter if the FDA does not agree that there is substantial evidence for efficacy. And the differences between FDA reviewers' conclusions and Biomarin's interpretations are gapingly wide for efficacy as well.
ISIS and ALNY unchanged, each worth about 8 billion, without any meaningful product revenue. Should KYNDRISA still manage to weasel its way to an approval it will join KYNAMRO as another black boxed white elephant with sales so low you'll never hear about them during an earnings call.
It is certainly possible that FDA needs to cover their collective butts and requires more and more kids to have biopsies going forward. I hope Sarepta can show FDA their lab bench results instead that justify the sequences that were selected and the associated exon skipping activities. That should do it. CG spoke of the genetic lottery with smaller and smaller number of patients. If you have a very rare mutation it would take many more years until Sarepta can start working on your PMO. Would they find appropriate patients in adequate numbers for even a very small trial? And then wait at least 24 weeks, perhaps 48 weeks for biopsy, and then analysis, and then submission, review, decision. There is a chance to SKIP all this with PMO medicines.
Even if the FDA will approve drisa, Biomarin will not be able to develop equivalent products for other exons. Too hard for them (=too expensive) to prove efficacy and acceptable safety for every product. In contrast, if etep gets approved, I see a clear road ahead for Sarepta that will, after exons 45 and 53 have been reviewed and approved, have the FDA agree to an unprecedented class approval status for all PMO sequences at 30 mg/kg for the treatment of DMD - for as many exons as Sarepta can cover. No IND enabling preclinical studies, no tox, no pk, no efficacy, nothing. Just give us the CMC information and you're good to go! IOW, etep decision is not just a huge issue for the 13%. It is instrumental for bringing safe treatment options to all DMD patients who could benefit from it, in a timely manner. Add that consideration to the list of issues to be considered once etep is up for its day in court.