I mean, if they just had a placebo injection and octreotide pill vs. an octreotide injection and placebo pill they would know. The octreotide injection is not stable since the effect decreases slowly and then rapidly towards the end of the month. I don't see how it could be double blind because the patients would absolutely know whether they were taking a placebo injection or placebo pill.
It would also the muddy quality of life assessment which is the critical factor in differentiation.
It's not so simple. You missed the first sentence:
"Upon completion of its review, the FDA advised Chiasma that the Agency did not believe the company’s application had provided substantial evidence of efficacy to warrant approval, and advised Chiasma that it would need to conduct another clinical trial in order to overcome this deficiency."
However, I believe that they can still overcome this issue, and possibly appeal the decision in a hearing, because the data to me seems incontrovertible proof of efficacy of TPE technology. I believe they could get a partnership as well, even with the CRL. Plenty of companies need this sort of technology.
Finally, just a quip, but "double-blind" does not mean "placebo-controlled". However, I still think double-blind is unethical because they'd be requiring subjects to either overdose or to dose with multiple injections towards the end of the month (when the once-monthly injection starts wearing off), which starts hitting an ethics issue rather quickly.
They didn't have enough drug at the start of the trial. DMD very rare disease. Not so much everything else you mentioned.
From what I have read, there's also an issue with the effect wearing off after a while... seems like for best results, one needs to alternate lanreotide and octreotide every few months, so a gradual reduction in efficacy is not unusual.
I am trying to get a petition to the FDA together. I wonder what will happen to SRPT. I almost pulled the trigger yesterday morning.
Your conclusion is not correct. The existence of an injection formulation does not mean that there is no unmet medical need. The injectable version has multiple quality of life problems which represents an unmet medical need:
1) A large percent of patients do not use any medication because they do not want the problems associated with injection. This, by itself, represents an unmet medical need.
2) The injection does not have efficacy for the entire month. Towards the end of the month, many patients need to take booster shots, sometimes thrice weekly and sometimes more than once daily, depending on severity. This severely compromises quality of life, which represents an unmet medical need.
3) For many of those who do take the injection (a painful 90-second shot in the buttocks), there is a lasting pain that lasts several days. Sometimes, an octreotide injection can be botched, causing the octreotide to harden into a lump and dissolve very, very, very slowly. The pain of the injection represents a severe quality of life issue and therefore an unmet medical need.
1) The platform can be used for 60 other indications. It is valuable.
2) FDA rarely changes their minds on anything due to the way that they do these reviews. It's based on consensus, so one individual cannot change the group consensus without serious backlash.
3) The company, at current cash burn, has enough cash for 1.5 years. The best-case scenario is that the FDA allows accelerated approval based on an unmet medical need (since a large number of acromegaly sufferers go untreated), or that the FDA decision for an extra P3 trial is reversed within 1-4 months.
If FDA does not budge, the best thing the company can do is to cut all of its sales staff, which is most of the company, and reduce its executive head count and salaries. That way its cash burn will be closer to $20m a year instead of $86m. At 20m, cash runway will be 6-7 years.
Worst case is that the company cuts staff, but not enough, and dilutes in a year.
4) The EU (EMA) trial, which started a month ago, needs to be either modified or the FDA demands need to be modified, because FDA wants a double-blind trial (dubiously ethical), and the EMA trial is open-label. The EMA trial was scheduled to complete in 2018 with the EMA review process completing in late 2018. However, they will likely shorten it by several months (if not a year) to reduce cash burn, and likely reduce the number of patients enrolled to 100 instead of 150.
I think the most likely scenario is that the FDA will not budge and the company will downsize to a 35m/year cash burn, likely keeping most execs and their high salaries. It's not something I want but it will still raise the price because right now the price is pressured by extreme uncertainty.
They can't yet. They need to speak with the FDA about it. The EU trial is randomized, but it is not double-blind (it is open label).
Yes. It won't be for a while as they only started last month. However, I highly recommend you go through the slides of the Barclays webcast, available on their site. That will give you a much better understanding of the company and its value proposition.