Complete Response Letters
A cluster of CRLs for rare disease applications based on one trial plus confirmatory evidence may represent a shift away from the regulatory flexibility that had come to characterize ultra-rare drug development
US FDA’s rejection of Biohaven’s troriluzole is a huge disappointment for patients with SCA and the company. But it is also a notable example of how communication strategies are changing now that FDA is making its ‘complete response’ letters public.
Meeting minute clarifications also are undergoing some modifications as part of Tidmarsh’s plans to increase efficiency and reduce workload with hiring slow going.
Recently released CRLs for unapproved products contain recommendations for new studies, including design element details and advice to consider in different submission pathways.
The agency identified deficiencies in efficacy evidence intended to support results from a single adequate and well-controlled trial for orphan applications, including weaknesses in animal data and insufficient quantity and quality of biomarker data.
The Pink Sheet breaks down the data on the 89 complete response letters recently released by the FDA, including by type of application and problems noted.
Saol cannot finance the new trial of its ultra-rare disease drug that the FDA required in a complete response letter, but hopes to leverage a 12-year history of collaboration with the agency to devise another path forward, company executives tell the Pink Sheet.
The FDA's release of CRLs for unapproved products could bring a court challenge, but for now, sponsors should expect all past and future letters will be made public, experts said.
Pink Sheet editors discuss the recent departure of a noted vaccine expert and many others from FDA advisory committee rosters, as well as the details and potential impact of the FDA’s release of dozens of complete response letters for unapproved products.
The US FDA’s unprecedented publication of 89 recent CRLs for unapproved products comes with a promise to release future letters more promptly.
The complete response letters call for a new trial for PTC’s vatiquinone and more confirmatory evidence for Outlook Therapeutics’ Lytenava, while Telix’s Zircaix CRL shows quality challenges for a novel radiopharmaceutical approach.
The agency is expected to give its final verdict on the Barth syndrome drug by the end of September. Stealth is seeking accelerated approval based on the path forward outlined in the FDA's May 2025 complete response letter.
The Pink Sheet takes an exclusive look at the complete response letter, which shows the information on application deficiencies that could become widely available if FDA leaders succeed in releasing CRLs in real time.
The Pink Sheet viewed Stealth's complete response letter and other documents indicating the FDA appears willing to grant accelerated approval to elamipretide before a confirmatory trial begins enrolling. But the company says it needs a two-month review of the NDA resubmission to survive.
Ultragenyx said talks with the FDA about a path forward after receiving a CRL for UX111 have been productive despite the recent upheaval at the agency.
The US FDA says its release of complete response letters for products subsequently approved by the agency is just a first step toward releasing rejection letters when they are issued, assuming legal issues can be resolved.
Replimune's RP1 oncolytic immunotherapy became the third regenerative medicine to receive an FDA complete response letter this month as the agency appears to re-visit previous agreements about accelerated approval.
The 43 novel agents with user fee goal dates in the remainder of 2025 have fewer oncologics and infectious disease drugs than the first half of the year.
US FDA's 25 novel approvals in 2025 fell short of the agency's five-year average count, driven by a drop in drugs center approvals; 45 user fee goals remain in second half of year.
Seven weeks before its action date and a month after an advisory committee was hastily cancelled, Capricor gets a CRL for its cell therapy deramiocel in DMD-related cardiomyopathy citing efficacy and manufacturing concerns. It has a Phase III study nearing readout, though.