bet - you bring up a great point and hammer it home with one of my lesson-learning trades. I had some shares in UTHR prior to approval and the price didn't move much when they got FDA approval - maybe 15-20% if I remember correctly - so I sold it. I didn't understand at the time what these orphan drugs were potentially worth, so I missed out on a 20X+bagger. As Ed Kaye has stated, SRPT is going to own the DMD space. These days, investors are more in tune with the orphan drug space and potential values, so a 20X return is probably not in the cards from here, but anyone who sells for less than $100 will surely miss out on some easy money.
I read the article - the guy is seriously delusional - he basically says if you exclude all the patients that did poorly on the drug the data looks great and when it comes to safety, the serious adverse events were in a "very small number of patients" and are "manageable" in the context of a lethal disorder - how would the very small number of patients changed if not for all the drop-outs and discontinuations. I suppose until they get rejected in Europe, he has to continue to posture for Drisa - after they get rejected there, I would hope for his shareholders' sake he would pull the plug on entire platform - there is no way Drisa can get to market without additional trials and who is going to enroll in them if Etep is approved?.
The quote in the Business Journal was him commending the FDA on how they handled the Drisa review. I've listened to every presentation and conference call over the last 4 years and I don't recall CG ever disparaging the FDA - he may have expressed frustration with the process and their start and stop decisions, but he was mostly disciplined in his comments about the FDA and how the company needed to work with them. CG was a scapegoat for people who though the FDA was making decisions based on personality conflicts with CG - if you look at the evidence, the FDA's decisions were based on ignorance and bad analysis.
Please provide examples of CG's "loose talk" - did he say something offensive about the FDA or their process - what exactly are you referring to when you conclude his loose talk got him fired?
"hopefully this is nearing completion" - it is highly unlikely the company has sold any shares through Cowen, yet. First off, they haven't even publicly announced the ATM agreement with Cowen - there has been no press release and they didn't discuss it at the recent Stifel conference - selling shares without a public disclosure is highly unethical and not consistent with the company's actions in the past. They also announced at Stifel that they are in the process of validating the "event" data from the two Phase III trials, so selling shares during this time frame would be an even more egregious act. Finally, there has only been five trading days since the Cowen agreement was disclosed in the SEC filing and the volume during that time has not been out of the norm (~850,000 shares per day).
The more likely agenda is that knowing they would be releasing top-line data around year-end, they wanted the ability to efficiently raise some funds to support the commercialization of Evo. Every action the company and Merck have taken over the past year is consistent with the expectation of a drug launch. While the data may still be officially blinded, they have some knowledge from the clinical sites how many patients are still being treated with Evo and for how long, so they have an idea which way the data is going to fall. For example, in the STS trial, the top-line results are based on 434 deaths out of total enrollment of 640 - they know how much drug they are shipping to the clinical sites and how that relates to the 200+ remaining patients in the study.
md - I don't mind someone "looking at both sides", but when the writer either ignores the relevant facts that would render one of those sides senseless or is ignorant of the facts, while portraying himself as an expert, then I think the criticism is justified. I am actually on the fence about AF - I have seen him make some very reasonable analyses of the validity of a certain company's drug or trials, but when it comes to SRPT and Etep, he has been very flaky with his analysis and has ignored some fairly evident facts, so you have to question his motives?
jrrt - given the harshness of the FDA assessment on safety and lack of mechanism of action, it would almost be negligent for BRMN to continue with their DMD platform. It is difficult to imagine the FDA actually asking them to do another trial to prove effectiveness, given their safety assessment. The FDA forced the AdCom's hand into focusing on the data flaws and safety issues, rather than the unmet need and patient testimony - will they force BMRN's hand and say don't come back until you can prove you can dose this safely in a preclinical trial?
When it comes to the issue of IV administration, I thought that the reason they didn't use that route originally was it was too harsh for IV - the risk of vasculitis was too high? No doubt SC provides some convenience, but when you are trying to get the drug dispersed to every corner of the body, I can't imagine SC is effective at that?
I agree - BMRN is a turd, but a $20 drop in the share price equates to a loss of ~$3B of their $15B+ market cap - I don't think the "market" was imputing a $3B value on Drisa and the rest of their DMD platform. The argument for a $20 price decline would be that if the CEO and exec team were stupid enough to waste $700M+ in buying RNA and were shady enough to exaggerate its clinical benefits while minimizing the clear safety risks, then what other holes in their pipeline are yet to be revealed?
When Drisa is formally rejected in late Dec we move into the $45-$50 range. After the Jan AdCom for Etep we move into the $70 range and after Feb approval of Etep could breach $100 - depends on how patent issues in Europe play out?
I was thinking the same thing - when the AdCom brought up the idea that the ISRs were effectively unblinding the study and asked whether the boys with ISR performed better on the 6MWT - how is a boy in pain and/or with an ulcer on his leg or butt supposed to perform better?
copp - I agree on the face of it that the Etep data is strong enough to get conditional approval without an AdCom, but I think the FDA wants to avoid any controversy and put the process out in the open. It is such a politically charged decision and there are so many "vested" interests at play, any sign of favoritism or working outside the designated process would put them in an unfavorable light. I was actually impressed how emphatically they exposed Drisa's flaws - hopefully they will be equally impressive in acknowledging Etep's distinct advantages to Drisa and make it the case book example of FDASIA that it deserves.
jrrt - In the case of Drisa, I think the FDA just wanted the data and their breakdown out in the open. The case made by BMRN for their data vs the FDA's interpretation of the data was night and day - if the FDA had rejected Drisa behind closed doors, the parent groups would have gone crazy. I agree that they did not want any wiggle room from the AdCom members to interpret the data in a positive manner - the questions were set up to focus on the true flaws in the data and not to look for any potential silver linings (there were none).
One of the most shocking comments from one of the AdCom members was a woman (Gunvalson) who said if she was a DMD mom, she would accept the 10M benefit computed for Drisa from the Phase III trial. Obviously, this was an emotional statement, because it truly ignored the reality of that reported 10M benefit, in that it came from a trial with a P-value of 0.42, which means that the value was statistically meaningless. You would hope someone on an AdCom would understand basic statistical concepts, but if she didn't, the FDA was validated in not letting emotions come into play with a simple approval vote.
Exactly - I wish I had picked this up when it was below $2, but anything below $2.50 is still a bargain. With the offering, they have enough cash to get them to a couple of milestones that should push this over $5 in the second half of 2016.
thig - in my head I agree, but I sense that the AdCom will become "reactionary" to some of these issues. I am not worried about the N=12 issue - the N is only a problem if your data is inconsistent - BMRN was arguing to look at subsets while ignoring the other patients for reasons that upon analysis didn't hold up. I am worried that the dystrophin production evidence may not sway, simply because it was noted several times that Becker patients typically have dystrophin positive fibers of 50%+ - I don't believe SRPT's positive fiber counts made it to that range. Many AdCom members were questioning not only what level of positive fibers were necessary to provide benefit, but how could they be sure the dystrophin being produced by Exon-skip was functional. I know SRPT has additional tests and data on these issues - let's just hope they are convincing.
Regardless, I still believe that SRPT's safety profile and efficacy data is sufficient for a conditional approval and the progress they have made in the confirmatory trial should seal that decision.
BTW - A long day and a celebratory IPA caused me to add a decimal place in my example of BMRN's dystrophin production fantasy - the 4% increase from a baseline of 0.5% would be 0.52% The point is still valid - their dystrophin production numbers were a joke - it is hard to believe they were discussed at all, although several AdCom members noted how unethical it was for all the useless biopsies they took from these boys - in their P3 trial only 44% of the biopsies were able to be read.
BMRN created. Their efficacy data was so full of holes and their safety profile was so horrible, this drug should never have been submitted, but as was noted numerous times on this board, the FDA's acceptance/filing of their NDA was no indication of the quality of Drisa - it simply meant they had met all the requirements documentation for a NDA. You could tell the AdCom members were desperate to find any positive thread to the data, but it just wasn't there. I actually felt bad for the FDA staffers who had to get up and publicly display how worthless BMRN's data was - they were put in a horrible position of trashing the hopes of the few patients who actually believed in the drug.
The one interaction that to me epitomized how desperate BMRN was to fool someone into believing in Drisa was during the discussion of dystrophin production. The FDA staffers made it pretty clear from the start of the analysis that the dystrophin increases that BMRN was reporting were small percentage increases (less than 5% increases) from baseline readings that were less than 1% of normal muscle tissue. In other words, BMRN was trying to rationalize that an increase from say 0.5% of normal at baseline to a post-treatment reading of 0.502% was meaningful. When one of the AdCom members asked if they had analyzed whether the increases in dystrophin correlated to any increases in 6MWT performance, they actually had a chart prepared - even the idiot AF commented "why didn't they show this earlier"? Answer - because anyone that believes that a .002 increase in % of dystrophin positive fibers would correlate to anything is a moron. The fact that BMRN put a chart together answering a question only a moron would find meaningful says a lot.
The downside to this whole debacle is that regardless of how strong the case is for Etep's conditional approval, it is now soiled by being linked in the minds of many analysts and "experts" as a drug that is similar to Drisa - What A Mess!
The scary part is the trigger was the investment by one of the more vile characters in the hedge fund space - given this guy's track record as a scumbag, who in their right mind is jumping in thinking he has any ability to do anything but rape the shareholders?
"repeatedly raised concerns" about N=12? If they had any problem with N=12 in the context of an accelerated approval they would have closed the door years ago - I don't recall any correspondence or communications where N=12 was deemed a problem. When it comes to dystrophin production, what the FDA expressed was ignorance - they challenged SRPT with false accusations of how their methods were lacking (without providing any specifics), but then SRPT proved them wrong with the re-reads and the 4th biopsies.
More paranoid, vacuous drivel from simp - what else is new?! Instead of posting a laboriously lengthy message to get a single point across (Etep's briefing docs may not be glowing), why don't you give one or two specific areas where the FDA may find the data on Etep lacking or inconclusive? If the board were to post a briefing doc on the accuracy/relevance of your posts over the past few years, it would be as bad and conclusive as BMRN's!
It's a textbook example of how toxic Drisa is - if it can cause that much damage to the skin, just think what internal damage it can inflict over years of dosing?
Amen md - as Jenn has stated, Etep could have and should have been approved two years ago. Any analyst that dismisses the "limited" data on Etep as unworthy of approval is both clueless to the clinical evidence, dismissive of reams of anecdotal evidence, and insensitive to the irreversible destruction of DMD - to think the FDA would take another step back after all the hoops they made SRPT jump through (which they have done successfully) is just plain stupid.