Many questions remain unanswered. In the last ten months, have the leaders minimized the problem that the stability of the product weighed in the discussions with the agencies? (Photo credits: Adobe Stock)
If the title of the release was rather delicate, evoking a "regulatory update", investors reacted brutally, sending the stock price to the carpet. The FDA is recommending Pharnext to conduct a new phase III clinical trial for its flagship product Pleodrug PXT3003 (Syngility in Europe), developed in Charcot Marie Tooth Disease Type 1A (CMT1A).
A blow for the Parisian biotech that expected to file its application for marketing on both sides of the Atlantic, by the end of the year and was on a commercial green light from 2020. The position of the US health agency is explained by the stability problems of the drug candidate formulation encountered in clinical trials. Recall that in phase III, in a trial involving 323 patients, the product had demonstrated efficacy against placebo, only at the highest of the two doses tested and that the cohort of patients who received this dose had to be reduced to only 55 subjects, due to stability issues.
If it does not seem aberrant a posterio that the FDA has ticked … it is surprising that it took so long to raise the yellow flag. As early as 2017, Pharnext had reported this problem and amended the protocol of his test. The cohort had been reduced and withdrawn patients had received a low, equivalent double dose. In October 2018, when the first phase III data was released, biotech still reported the problem but presented results, obtained on the cohort, that were valid and "consistent in various scientific models".
Many questions remain unanswered. In the last ten months, have the leaders minimized the problem that the stability of the product weighed in the discussions with the agencies? Or, more simply, have the statistical restatements, after amendment of the protocol, been quite rigorous? Or, the FDA, perhaps disrupted during this period, by the shut-down or these changes of direction, has it suddenly changed its analysis, seven months after granting PXT3003 the fast-track status.
Finally, will the agency require further study or a new phase 3 complete (with a single dose of course)? Answers will depend on the time and money that Pharnext will have to find to continue the adventure … And its stock market valuation of the company. "Given a low clinical risk, given the data already obtained, and the non-toxicity observed so far, the company could even seize the opportunity to test, in a new trial, higher doses" suggests even a optimistic analyst.
But leaders will first have to demonstrate strength of conviction and probably imagination to limit the breakage, reopen prospects for their flagship product, and mitigate the dilution that will inevitably accompany the further development, that it passes through an industrial partnership or fundraising.
Biotech Finances – "Biotech Finances is a specialized media on the French ecosystem of biotechs and medtechs"