FDA has two types of post marketing information collection and submission categories: Post marketing requirments (which is what FDA can require) and post marketing commitments, which co agrees to. One type of post marketing "requirement" is for confirmatory studies, called Phase IV, after accelerated approval. This seems to be what is going on, tying the shoelaces before letting eteplirsen take the boys amenable to Exon 51 out for a walk, which hopefully will last several years. See the FDA website on post marketing requirements (PMR) and commitments
"Morpholinos are also effective to modify pre-mRNA splicing and to inhibit miRNA (Morcos, 2007). These oligonucleotides offer the prospect of a safe and effective therapeutic for a broad range of previously 'undruggable' diseases that include Duchenne muscular dystrophy (Moulton et al., 2009), Huntington disease (Sun et al., 2014), cancer and cardiovascular diseases (Templeton, 2015), Ebola (Heald et al., 2014), etc. Many of the morpholino-based treatments are currently undergoing clinical trials and are showing impressive safety and pharmacokinetics results (Sanghvi, 2011). "
Once platform validated with Exon 51 approval, other disease pipeline will be valued
What is the expected form of the transaction that maximizes shareholder value? Not just a sale, but a reverse spin that minimizes tax liability by providing a business purpose for the new shares to be distributed tax free with new bases determined based on relative value of assets represented??
Captain Mary Kremzner: Now Cat, exactly how does the FDA determine when an expedited approval is warranted?
Commander Catherine Chew: Generally drugs are approved under Accelerated Approval if they have the potential to impact factors, things like survival, day‑to‑day function or the likelihood of stopping a disease from progressing and becoming an even more serious condition.
Captain Mary Kremzner: Now Cat earlier you mentioned filling an unmet medical need. How would you define that?
Commander Catherine Chew: An unmet medical need simply means providing a therapy when none exists or providing a new therapy that may be superior to or less toxic than an existing one.
Captain Mary Kremzner: So without the standard clinical outcomes how does FDA determine if a treatment is potentially effective?
Commander Catherine Chew: Great question Mary. Accelerated Approvals use what we call a surrogate end point in clinical trials. These are markers or a physical sign of sorts used as an indirect measurement to predict a clinically meaningful outcome like survival or symptom improvement.
Captain Mary Kremzner: So exactly how does the surrogate end point save time in the drug approval process?
Commander Catherine Chew: Well for example, instead of having to wait to learn if a drug prolonged survival in cancer patients the FDA has approved drugs based on evidence that they shrink tumors. As a surrogate end point, tumor shrinkage is reasonably linked to real clinical benefit.
Captain Mary Kremzner: Okay, so let me make sure I have this. Let’s say a drug goes through Accelerated Approval and gets to market, how do we know if it really provides that clinical benefit?
Commander Catherine Chew: Any approvals given based on surrogate end points are on the condition that the sponsor will conduct post-marketing clinical trials to verify the anticipated benefit. If these trials, called Phase 4 Confirmatory Trials, shows the drug does in fact provide a clinical benefit then
Sites are currently being initiated into the study. Initiation of approximately 39 planned sites in the United States is expected to be completed by June 2016. The initiated sites can be found in the "Contacts and Locations" section of this posting in addition to a listing of the city and states of sites the investigators are working to initiate. T
FDA needs to post the transcript - now about 7 weeks, even for an extended day, should be available.
I want to see the text where one of the AdCom members says I don't want to have a standoff between the Committee and the FDA and the Chair, Caleb A. says, I think you meant between the committee and the applicant, when what the member accurately really meant was, we don't like the FDA's approach and questions.
Sarepta has been supposedly been negotiating Pediatric Investigation Protocols with Europe for sometime. when are those finalized?
Approve Eteplirsen, stabilize Exon-51 amenable patients, proceed with 45, 53, other exons
This will delay progressive decline, stabilize patients for a few years
Develop a better PPMO, third/fourth generation AONs,
Develop a myostatin to restore, not just stabilize muscle.
Art Krieg knows his biotechnology
Art Krieg @ArtKrieg 2h2 hours ago
$SRPT from Ed k: if all continues well, PPMO could be in human DMD in ’17. Etep works, 0.9% dys helps; I believe PPMO should give 10X dys
Who said it was a margin account. My fully paid accounts don't let shares be borrowed without my permission. Go back to tweeting about your $150 profits from a successful fade. Titan will be at $30 before its at $5 again.
16-02 Associate Director, Medical Writing Cambridge, Massachusetts, United States 5/20/2016
16-03 Director/Sr. Director, Medical Writing Cambridge, Massachusetts, United States 5/20/2016
16-01 Senior Director, Biometrics Cambridge, Massachusetts, United States 5/20/2016
Lack of a treatment for Exon 51 amenable skipping DMD patients
FDA reluctance to use patient registries for comparative information
FDA reluctance to use AA for diseases outside of HIV and Cancer
FDA insistence on bureaucratic control of patient access to new precision therapies
FDA lack of use of biomarkers for AA unless validated biomarkers (years of proof)
FDA contribution to high drug prices by extending valley of death for over-extensive clinical trials
Lack of treatment for 80 percent of DMD patients amendable to skipping other exons.
Something like this, depending on the broker
You need under Reg T something like a 50% initial margin. All this and the following depends on the broker. Then additional margin at say 30% will be required based
upon the changing value of the shorted stock. So say you short 1000 shares of Sarepta at 20, you would
have to have in the margin account $20,000 plus a 50% margin or $30,000 with $10K margin to start.
If the price goes up $5, to 25, the margin requirement is $25,000, plus 30% of 25, or $7,500, for a total
of $32,500, so you get a margin call for $2500 - you had $30K to start with, remember. Maybe you can come up with another $2500, so you have total account plus margin of $32,500. But it goes up another $10 per share.
Now the total value of the short position is $35,000 (1000 shares at 35) plus 30% or $10,500, so your total
margin account requirement is not 32,500, but $45,500, or another $13,000. If you don't come up with that
when requested, the broker will sell you out. The 30% maintenance margin reqt could be higher or lower depending on broker. Have a hunch some brokers will be raising the 30%. So little guys will not survive, only big deep pockets will be able to push a lot of chips in on the table as the price goes up, unless they decide to get out. Do your own diligence, but this is not a stock to short for small hands and bet against a safe, effective treatment for a significant unmet medical need which will MakeDuchenneHistory.
inadequate resources for 2 drug reviews, snow, missing adcom members, opaque and leading questions, 100 members of Congress, 24 Senators, major amendment with positive 4 year data, reports of CRO benefits from study 204 on falls. ADL, 36 experts, 6 doctors and therapists reporting patients benefitted, Adcom comments "it ameliorates the DMD phenotype" "from everything I heard today the drug works, but that wasn"t the way question was phrased". Be Reasonable
Chad Onyike asks, to what extent are we supposed to incorporate the testimony of the patients and others
the wording makes it seem a statistical question
Woodcock; We are supposed to incorporate patient viewpoints
Temple; You heard testimony from patients that tests didn't affect their level of effort
Unger: Unprecedented to have basically all the patients here. We're hearing patients improving doing
things they didn't do last year.
Romitti Q: We have 2 different groups, are we supposed to consider dystrophin results
Woodcock: this is the full approval question, not based on surrogate endpoint
(a mistaken description - dystrophin could be confirmatory evidence of single arm HC control trial)
Temple, Historical trials can be adequate and well controlled, some obvious, some not so clear.
Dunn: thats why we discussed historical controls, evidence from trials plus info from patients can be substntial evidence:
(So for 10 minutes they discuss, what does this question mean, can we consider patient and expert testimony....obviously the question unclear and basis for voting was not well defined)
Foley: Yes -clearly ameliorated the DMD phenotype.
Ovbiagele: No, but from everything I heard, this drug works
Hoffman, Green, Romittee: abstain, don't want to make a type 2 error, fearful of stalemate between
FDA and panel
Gunvalson, Dupree: Yes-can't reconcile difference between testimony boys are improving
Kryscio, Nuckolls, Kesselheim Onyike, No, not well controlled, but there seems to be more informatio from further studies showing benefits not included, use CROs like dementia (but they had 5-6 clinicians testify?)
Dunn FDA final comments: have listened very carefully, seen AdCom highly influenced by testimony, will consider very seriously
(So vote was again 6-7 with 3 abstainers sympathetic but restrained by "statistical" question-w Ovbiagele
saying drug works, basically 7 in favor of approving drug if asked based on all heard from patients & doctors)
Definition of a bear trap: Stock goes up in anticipation of approval, shorts pile on for quick .50 drop they hope, get stuck with FDA sudden decision and lose $30 per share short.
So that they can differentiate Eteplirsen showing no risk and some benefits when they grant AA. Sample Eteplirsen Benefit risk in Sarepta presentation and on twitter.
Things that take time
1. Labeling see guidance on labeling for AA
2. writing final structured risk benefit - released with approval
3. agreement on confirmatory trials timing/controls/size
Yes, it may sell a ton of stock, to BigPHarma - see story from Fitch Drug approvals driving targeted acquisitions in US pharma, says Fitch PFE, BMY both would be looking closely at marketable drugs and PMO IP and pipeline