It's worse than that, Simp. Remember, GSK/RNA didn't even take baseline readings on Dystrophin. There are none. So how is anyone supposed to conclude that the patients in their trial showed increases in Dystrophin? Increases from what? An imaginary baseline?
That was me in the last post, accidentally using a defunct ID that I retired years ago.
The other thread was getting too messy, and I didn't want to lose an important point. Slides of the PTC study are found on their website. PTC is developing Ataluren for a form of DMD caused by different genetic defects than those targeted by Sarepta's eteplirsen. Ataluren (which I hope works, and it does not compete with Sarepta) showed a stronger treatment effect under for trial participants with baselines under 350m (they call this the "decline phase"). Therefore, it was crucial that PTC strenuously argue that results of children with baselines over 350m should be ignored. Keep that point in mind.
In the graphs depicted, it is clear that patients UNDER AGE SEVEN did not decline if their baseline was over 350m. However, over age 7, the picture changed dramatically. Even though PTC admitted unusually healthy patients, most with baselines over 400, 55% of those over age 7 (11 of 21) declined, some rapidly. Thus, no unbiased researcher could conclude that patients over age 7 and above 350m could be expected to be stable. However, the PTC researchers were not unbiased and they trumpet the "350m=no decline" conclusion on several consecutive slides. Why? Again: Their drug apparently only showed clear effectiveness with patients under 350m baselines (which they call the "decline phase" ). Therefore, PTC needs investors and regulators to ignore the results tested above 350m. Thus, they disingenuously lumped in the younger kids with the older kids, using the health of the younger kids to skew the results and argue that overall kids over 350m baselines don't decline--a conclusion their own data disproves.
Why is this important to Sarepta? Because 1) the FDA apparently bought the PTC conclusion. 2) the Sarepta trial had no children under seven. 3) the Sarepta trial had no children over 400m baselines. 4) the Sarepa trial kids have different mutations.
Jrrt1, Check twitter. Someone under the name @hamfighters has posted a photograph of a slide from the PTC study. It concludes that those over 350m are not expected to decline significantly. However, as has since been pointed out, if you examine the photo more carefully, the slide shows arrows representing individual patients. The patients under seven all have arrows that are stable or pointing up. However, as the patients get older, a curious thing happens. The patients over 400m, including some WELL over 400m and even over 500m, have stable arrows, even over age seven. However, those that fall between 350 and 400 simply do not. The graph clearly shows that those over 7 between350 and 400 baselines are declining. It is extraordinary that the researchers posted a bogus claim without noticing that.
The FDA statement is rubbish. Not only do all natural history studies support Sarepta's model for decline, but you can now add to that Prosensa's P3. It had a ton of patients across all age groups, and they all declined, just like natural history studies have predicted. Nothing supports the FDA's statement. It came out of the blue, conjured up by bribed bureaucrats trying to cover up the tracks of their corruption.
The FDA isn't angry. Just corrupt. Someone bought them. Something needs to be done.
I agree with all the commentary here. What the FDA has done is indeed criminal, not merely metaphorically, but likely literally. The abrupt about-face is fishy to say the least. In July, the FDA gave SRPT the thumbs up for early filing. Subsequently, SRPT strengthened its case with BETTER data. And yet the FDA changed its mind, allegedly based on a Prosensa press release or on natural history data by a researcher who himself unequivocally believes that SRPT works? There was no rational basis for this. Someone at the FDA--perhaps more than one--was bought.
Thanks, patriot and Thig, I was so focused on the recent revelations that I completely forgot about the old targets. Later on, I'll try to do an updated list. Not sure if I should include the terminated trials, though. Does anyone have any information on those? Were Coronary Artery and HCV terminated out of financial considerations or for concerns about efficacy?
I thought I'd organize things a little, as SRPT refuses to simply announce all of their targets and put them all on a pipeline website. Here's what we know:
Targets well advanced:
DMD--exon 51. Market potential in the 0.5-1.0 billion range.
Targets fairly far along:
Marburg (potential unknown, although TKMR has spoken of 300+ million stocking orders from gov for Ebola)
Targets in earlier testing:
Flu (probably multi-billion dollar potential)
DMD--additional exons in preclinical
Other targets for which preclinical work is/has been done:
Beta-Thalassemia--source: Nature (orphan indication: mkt potential unknown)
drug resistant bacteria--source: The Oregonian, I think (mkt potential apparently growing rapidly)
Progeria--source: SRPT patent on progeria mutated gene Lamin A (orphan indication: mkt potential unknown)
Targets in which company has expressed interest, likely to have done preclinical work:
Huntington's disease--source: Bloomberg (orphan indication: mkt potential unknown)
Spinal Muscular Atrophy--source: Bloomberg (orphan indication: mkt potential unknown)
Likely other targets mentioned in Nature but not expressly assigned to SRPT:
Niemann–Pick type C disease
I'm pretty confident that this list is correct, as far as it goes, but I'm not at all confident that it is complete. Hopefully, someone such as pineappleguava, who maintains excellent records, will see this and offer any needed corrections or additions. In the meanwhile, I've got to say this is one heck of a promising platform company. DMD as "proof of concept" and nine other orphan targets, two deadly viruses, and an unknown number of flus and cancers to target. Incredible. Eteplirsen may end up merely funding one of the great pharmaceutical companies of all time. I just really hope the company picks up its pace and starts launching more trials.
Sentiment: Strong Buy
Guys, guys, don't let the shorts sucker you in to worrying about non-existent problems. We don't need individual patient data to prove there were no outliers, because the topline results already include both minimums and maximums. If one kid were an outlier, he'd show up with an outrageous maximum. That hasn't happened. Nothing to worry about here. The shorts are sounding increasingly amateurish and desperate in their attempt to spread fear.
First, background for newbies: The 12 boys in the eteplirsen trial underwent three painful biopsies to test for new dystrophin production. Putting DMD kids under sedation is inherently risky and not something undertaken without great consideration.
Very recently--in fact, after Sarepta's last formal meeting with the FDA--the FDA requested that SRPT perform a fourth biopsy on the kids. This unusual request seems to hint that the FDA is STRONGLY considering approval based on the phase II data. But the parents want that guaranteed before they agree to put their kids under the knife (and sedation) one more time. Here is a key paragraph from the Jett Foundation blog by DMD parent John Campbell (published Sept 23):
"3. Accelerated Approval – The discussion around the 4th biopsy request should be met with a stiff agreement by the parents of the children in the trial. The children should not be subject to an additional biopsy, however, if the parents choose to agree – there needs to be a clear and direct benefit to the community, it needs to be understood that if the data continues to show evidence of dystrophin, and the boys in the trial continue to be stable – that dystrophin as a surrogate marker should be accepted, and therefore accelerated approval granted."
I wouldn't try to raise expectations for something spectacular at 96 weeks. All we are looking for is stability/slowed decline. That's the best we can hope for. Raising the expectations bar higher than that will simply set the stock up for disappointment no matter how solid the results are.
Today's move is a continuation of the short covering that began on Friday.