Celgene late Tuesday announced a setback for one of its most promising investigational medicines when it received a refuse to file (RTF) letter from the US Food and Drug Administration (FDA), setting off a flurry of questions for the company that may not be answered publicly.
According to Celgene’s press release on receiving the letter, the company said: “Upon its preliminary review, the FDA determined that the nonclinical and clinical pharmacology sections in the NDA [new drug application] were insufficient to permit a complete review. Celgene intends to seek immediate guidance, including requesting a Type A meeting with the FDA, to ascertain what additional information will be required to resubmit the NDA.”
In December 2017, FDA released new draft guidance
on RTF letters, explaining that the agency exercises such an authority “for incomplete applications to optimize the use of both the applicant’s and the FDA’s resources. RTF actions allow the FDA to notify applicants of application deficiencies as soon as possible, rather than waiting until the end of a review cycle and notifying the applicant in a complete response letter.”
RTF letters are issued not because the data in the NDA is inadequate for an approval, but, as FDA explains
, because of “omissions of clearly necessary information (e.g., information required under the statute or regulations) or omissions or inadequacies so severe as to render the application incomplete on its face and where the omissions or inadequacies are obvious, at least once identified, and not a matter of interpretation or judgment about the meaning of data submitted.”
And when Celgene says it has requested a Type A meeting, such meetings are reserved only for a stalled product development program to proceed or to address an important safety issue, and must be requested within 30 days of receiving the RTF letter, according to FDA guidance on such meetings
Celgene vs. History
Jay Backstrom, chief medical officer and head of global regulatory affairs for Celgene, said in a statement: “We remain confident in ozanimod’s clinical profile demonstrated in the pivotal program in relapsing forms of multiple sclerosis.”
And if history is Celgene’s guide, Backstrom is right to remain confident as RTF letters can be a minor setback ahead of FDA approval.
review of other companies receiving RTF letters shows that more recently, companies have struggled to win quick approvals though many companies have received RTF letters and still gone on to win approval for their products.