Disc’s uncommon illness drug hit by FDA rejection

Whereas the company agreed that Disc’s bitopertin had hit the first endpoint in an ample, well-controlled trial, the regulator took difficulty with the trial’s use of a surrogate endpoint instead of scientific outcomes, in response to the rejection letter (PDF). 

The section 2 trial that fashioned the majority of Disc’s approval software enrolled 75 sufferers with erythropoietic protoporphyria (EPP), a uncommon genetic illness the place molecules known as protoporphyrins construct up in purple blood cells, inflicting ache when uncovered to the solar. The situation may result in liver illness. 

On this randomized, placebo-controlled trial in addition to one other open-label examine that additionally fashioned a part of the submission, Disc used a drop in ranges of protoporphyrin IX (PPIX) as the first endpoint. The FDA agreed that each trials achieved their objectives however known as the 40% change in PPIX seen within the randomized trial’s high-dose arm “comparatively modest.” 

“Whether or not that magnitude of change in entire blood metal-free PPIX within reason more likely to predict scientific profit is unknown,” the company mentioned in its letter. What’s extra, each trials confirmed no proof that lowered PPIX ranges correlated with an improved tolerance of the solar, “regardless of the sturdy mechanistic and organic plausibility” of a connection. 

Massachusetts-based Disc believes it could possibly deal with the FDA’s considerations with its ongoing section 3 Apollo trial, the corporate mentioned in a Feb. 13 launch, which is about to enroll about 150 sufferers and is utilizing solar publicity outcomes as main endpoints. Prime-line information from the examine are anticipated within the fourth quarter of this 12 months, Disc mentioned. 

“Whereas our efforts at using expedited pathways to get bitopertin to sufferers rapidly haven’t come to fruition, we’re persevering with to pursue all avenues in help of FDA approval,” John Quisel, Ph.D., Disc’s president and CEO, mentioned within the launch. The rejection “will delay the potential approval of bitopertin, however we’ve confidence within the ongoing APOLLO trial, for which we’re seeing unimaginable enthusiasm from the EPP group.” 

In October, Disc was one of many first 9 recipients of a Commissioner’s Nationwide Precedence Voucher (CNPV), an opaque program promising speedy evaluations for “firms aligned with U.S. nationwide priorities,” FDA Commissioner Marty Makary, M.D., mentioned in this system’s June unveiling. 

Except for a generic antibiotic accredited in December, Disc’s bitopertin is the primary investigational drug to be reviewed by the CNPV pathway. 

The CNPV program has attracted intense scrutiny on account of its lack of transparency and considerations about attainable corruption and rushed evaluations. 

The rebuff is the newest of a sequence of FDA rejections, notably in uncommon ailments, a sample that has more and more been the topic of trade ire. Simply this week, the company refused to approve Regenxbio’s Hunter syndrome gene remedy based mostly on considerations about a number of trial design options, concerns which are sometimes addressed a lot earlier. 

“It is a systemic drawback that we noticed on the FDA final 12 months and proceed to see,” Biohaven CEO Vlad Coric, M.D., instructed Fierce earlier this week, citing his firm’s personal full response letter obtained on the finish of final 12 months for its spinocerebellar ataxia remedy. Although Biohaven had mentioned with the FDA in 2024 about utilizing real-world proof in a submission, the company in 2025 cited “points that may be inherent to real-world proof and exterior management research” in its rejection letter. 

That being mentioned, the company got here beneath new management in 2025, with President Donald Trump-appointed Marty Makary, M.D., taking the helm.  

Makary’s FDA has since been scrutinized for choices that return on prior steering or maintain probably helpful therapies from sufferers who don’t have any different choices.  

All this has created a extra tenuous regulatory setting, notably for drugmakers in sure illness areas or specialties. For vaccine builders, the FDA’s refusal-to-file (RTF) letter delivered to Moderna this week—regardless of the success of a section 3 trial—is forcing gamers to rethink their technique. 

The RTF resolution displays “how sharp the departure has been between the prior administration and this administration,” Mani Foroohar, M.D., an analyst with Leerink Companions, instructed Fierce. 

“I believe firms have discovered the pivot jarring, having developed medication and scientific trials based mostly on prior suggestions,” Foroohar mentioned. “It looks like a bait and change.”