FDA releases previously unseen CRLs in transparency push

The FDA's decision to publish complete response letters (CRLs) amounted to little more than a repackaging of existing information, but now it has gone a step further.

The latest batch of CRLs to be made public in the US regulator's drive towards what it calls "radical transparency" includes 89 previously unpublished letters, and comes with a promise to release future CRLs "promptly after they are issued to sponsors."

FDA Commissioner Dr Marty Makary trumpeted the decision as a "milestone" for the agency that will give "invaluable insights to help speed therapies and cures to market, providing complete context to investors and shareholders and, above all, restoring public trust."

Crucially, while the earlier release concerned only CRLs for products that were eventually cleared for marketing, the new batch included currently unapproved therapies, providing much greater insight into the FDA's reasoning for industry observers, investors, and other companies.

That said, all the CRLs that have been published are redacted to strip out any commercially sensitive information and personal private information, along the same lines as other published FDA correspondence like warning letters.

The decision to publish even these redacted versions has, however, led to questions about whether it is in alignment with current FDA regulations and could expose the regulator to litigation. It has also been speculated that the fear of sensitive information eventually becoming public could make it more likely that some applications are withdrawn, potentially placing a brake on innovation.

"Publishing CRLs offers important benefits for public health, including empowering drug developers to avoid common missteps and efficiently bring more cures and meaningful treatments to the American public; delivering greater insight to patients and the health care providers who treat them; and ensuring sponsors provide complete and contextualised information in communications to investors and shareholders," said the FDA.

The new batch includes the CRL last month for Replimune's RP1 (vusolimogene oderparepvec) in combination with Bristol Myers Squibb's Opdivo (nivolumab) for the treatment of advanced melanoma, as well as letters sent to Ultragenyx for its Sanfillipo syndrome type A gene therapy UX111and Capricor Therapeutics' Duchenne muscular dystrophy (DMD) cell therapy deramiocel in July.

A spokesman for one company whose CRL has just been published, psychedelic drug developer Lykos Therapeutics, has already used it as an opportunity to push back against the rejection of its MDMA-based therapy for post-traumatic stress disorder (PTSD) a year ago.

Lykos co-founder Rick Doblin, who stepped down after the CRL, welcomed the move by the FDA, but added: "Let's be clear: the CRL reveals a devastating truth — the FDA moved the goalposts." He claimed the agency selected a protocol for the phase 3 trial and then, after the trials were complete and the application accepted, shifted its position.