The initial biopsies were not "garbage" and the FDA did not "trash" them but reaffirmed the use of IMF for localization and quantification. What the FDA wanted was additional pathological review and WB/ELISA counts included. The "trash" as you state was a result of Biomarin crying that Drisapersen created no new dystrophin so Sarepta's PMO-induced dystrophin quantification methods must be suspect.
Besides proving the mechanism of action of an exon skipping oligo the last biopsy will disprove that the small population treated was due to variance inherent in the muscular dystrophy population. A stabilization or increase in dystrophin over the baseline three years out would prove the underlying MOA but shatter that the correlation to improved 6MWT scores Vs. historical data is due to increased or stabile dystrophin production. Dystrophin is the key to AA approval.
Sentiment: Strong Buy
by 4 independent pathologists equals 14% [+] fibers dystrophin @ 36 weeks. In context of 192 week dystrophin data confirms that the longer boys are on eteplirsen the more dystrophin produced. This suggests that many of the hypothesis' are correct including length of therapy, myogenesis etc.
I always thought that a percentage of ADCOM members would have a problem with the small treated population until today. This dataset is compelling and the ADCOM will recommend conditional AA approval this Q.
According to Ed Kaye Sarepta has corresponded with the FDA over 70 times since the NDA was filed in late June. This demonstrates that the FDA is not only well briefed on the data but is aggressively assisting SRPT in it seeking full FDA approval of eteplirsen. Even the Cowan biotech analyst, who was bearish on eteplirsen's FDA chances, was caught off guard by today's presentation and stated that these results are better then he anticipated. Are there any "shorts" left??
I can't recall another new drug application that was accepted by the FDA based on Phase II data when the subsequent Phase III trial failed. The failed Phase III dataset is included in the NDA so how does the FDA rationalize an AA approval when there is no proof that Drisa effects dystrophin production? A 6MWT that tracks with the historical placebo cohort and little reported about how this drug effects pulmonary Fx. or cardiac output. If I scratch my head any longer I'll have no hair left.
Sentiment: Strong Buy
JRRT, There was a 1 year study on the MDX mouse model utilizing the naked PMO and they discovered that dystrophin was produced in the heart [single digits] muscles of mice and cardiac function [output] was stabilized. STUDY: One-year Treatment of Morpholino Antisense Oligomer Improves Skeletal and Cardiac Muscle Functions in Dystrophic mdx Mice
jrrt1, Agree with your assessment. There are 2 sides to this deal. The brokerages want in now to realize much of the pending increases in share price and Kaye agreed. Once eteplirsen is approved and the other exons start to be priced into the market cap 3 million shares is minuscule.
jrrt1, Credit Suisse and Morgan Stanley is a big step up from the Rodman and Renshaw days. It will be virtually impossible , if one has an account with either one of theses houses, to receive any of these shares. Supply and DEMAND.
New research paper published highlighting peptide nucleic acids in the MDX DMD mouse model. Researchers believe that due to the clinic failure of Drisa an opening exists for PNA's. The authors conclude that PNA's are comparable in efficacy and safety of PMO's in DMD. PMO's are now the standard that other exon-skipping oligos will be measured against. What took so long? Link on twitter
Sentiment: Strong Buy
The serum half-life of eteplirsen is 3-4 hrs. which is in the zone of other non-extended release drug formulations. Eteplirsen's intracellular half-life has been reported to be as long as 54 days.
Sentiment: Strong Buy
Investors might conclude that I am crazy after reading this post but I interpret Biomarin presenting in late Nov. and Sarepta in late January a "win-win" for SRPT shareholders. Drisapersen will be voted down at their adcom based on logical reasoning. A Phase II trial advances to a Phase III when safety and efficacy has been suggested on a small to moderate size population. When a company like Biomarin files for AA based on Phase II data when the licensing Phase III trial failed, the burden-of-proof shifts dramatically against approval on an earlier and smaller population trial. Biomarin plans to suggest to FDA regulators that if they had dosed a younger cohort their drug would have met it's only endpoint, the 6MWT. I have reviewed their Phase II data [data that has been made public] and Drisa tracks historical non-treatment cohorts. The best that they can expect is that the FDA instructs them to run another trial to test their hypothesis. By the time Sarepta presents their case to the FDA 2 months later the FDA would have consumed and critiqued Drisapersen's dataset ad nauseum. The contrast between the 2 different drugs will have only grown. Eteplirsen induced AA biomarker dystrophin 14%-40%, 6MWT scores 151 meters greater then the filtered match historical cohort. stable to increased pulmonary Fx. scores and stable cardiac output scores at 3+ years. Look for Ed Kaye to provide additional safety and efficacy data from the ongoing Phase III trial up early january 2016. The FDA is on record of stating that Sarepta can submit any additional data at any time to support the case for eteplirsen approval. One of the many gratifying results from a + eteplirsen Adcom in Jan. will be to once again prove the conventional wisdom as expressed by uninformed biotech analysts and internet pseudo-journalists that just because Biomarin has some expertise in advancing Orphan Drugs through the FDA processes does not make a failed drug approvable.
Tred, Agree with your comments. Adam F. links the divide of Biomarin's Adcom hearing with an approval by stating, " Assuming that all goes well for Biomarin". This is all vacuous rhetoric linking drisa approval. Unbelievable.
Speed, Good pickup on Wilton's comments. If Biomarin attempts to get this by the FDA ADCOM panel they will be doomed but I don't think they [BMRN] are stupid. I predict they will not link dystrophin production to a correlation to improved 6MWT scores. They would rather disregard the mechanism of action questions by the panel then advance a knowingly dishonest presentation of Drisa induced dystrophin production WB tomfoolery.
I must admit that the following is not my thoughts but from another. I'm a little embarrassed i haven't thought of this and it involves Biomarin's final FDA approval, if achieved, and ultimate marketing discussions with the FDA. Based on Drisa's toxicity profile which is "significant" will most undoubtedly result in a safety REMS which will negate any time difference advantage Biomarin has in the marketing approval of Drisa. It is being advanced in analyst reports and internet journalism that BMRN will have a 2 month headstart in the race to sell their drugs first which conveys a huge advantage. Like most conventional wisdom, it is wrong, again.