Insmed (INSM) announced on Wednesday that the FDA has granted Arikayce (liposomal amikacin), the company’s lead product candidate, Breakthrough Therapy Designation (BTD) for refractory nontuberculous mycobacterial (NTM) lung disease. According to the company, the designation is based on Insmed’s phase 2 trial of Arikayce in NTM lung infections, which read out in late March and actually failed its primary endpoint. INSM is up 40% in trading on Wednesday.
Recall that in the phase 2 NTM study, Arikayce (590mg delivered once daily) added to standard of care treatment was tested against SoC plus placebo in 90 adult patients with treatment resistant NTM lung disease. Arikayce did not need the pre-specified level for statistical significance on the trial’s primary endpoint, a measurement of the change in mycobacterial density, though Insmed reported a positive trend.
Arikayce did achieve statistical significance on the secondary endpoint of culture conversion, with 11 out of 44 patients on Arikayce demonstrating negative cultures by day 84 of the study, compared to 3 of 45 patients on placebo (p=0.01). Insmed argues that this is the more clinically relevant endpoint, and the read-through for investors on Wednesday is that FDA is a-okay with the secondary endpoint.
Note that just one week after the phase 2 results, it was revealed that Dr. Renu Gupta, Insmed’s Chief Medical Officer (CMO), would be departing the company “to pursue other interests.”
Breakthrough Designation seems to be following in the footsteps of “Fast Track” and “Priority Review” designations: functionally beneficial, but losing consequence in the eyes of many investors as more and more therapeutics receive what was once lauded as a powerful new tool at the FDA. The agency defines BTD as “. . . a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).” Breakthrough Designation gives the company intensive guidance from FDA on an efficient development program and eligibility for rolling and priority review, among other facets. While clearly this is good news for the small company, investors would do well to consider BTD and similar designations incrementally beneficial, not game-changers, and certainly not absolute validation from the FDA.
Meanwhile, BTD and similar designations will remain poignant for small-cap biotech companies looking for the next great headline.
