Five corporations under scrutiny for navigating uncertainties within the Food and Drug Administration's regulatory framework

In a significant shift, the Food and Drug Administration (FDA) has introduced a new risk-based approach to COVID-19 vaccination, leading to restrictions on several vaccines, including Pfizer and BioNTech's Comirnaty, Moderna's Spikevax, mNEXSPIKE, and Sarepta's Elevidys. The latter has been linked to three reported deaths, causing the FDA to request a halt on all Elevidys shipments.

The FDA's move comes as the agency also approved Nuvaxovid for seniors aged 65 years and older, as well as people 12 through 64 years of age at high risk for severe COVID-19 outcomes on May 16. However, the recent changes have caused uncertainty among biopharma companies, particularly those seeking approval for rare disease therapies.

Sarepta initially resisted the FDA's request to halt Elevidys shipments but eventually complied. The FDA later recommended lifting the hold for ambulatory patients. This incident has sparked discussions about the need for a clear framework from the FDA to prevent biotechs from feeling like they are gambling with their limited funds, as stated by Rahul Gupta, president of AI/ML company GATC Health.

The FDA, under Commissioner Marty Makary, is implementing changes to speed up drug reviews and expedite rare disease therapies. These changes include the use of the Commissioner's National Priority Voucher, the establishment of a conditional approval pathway for rare disease therapies, and the ban of pharmaceutical representatives from some advisory committees.

The FDA's new approach has also affected other companies. Ultragenyx, the pharmaceutical company behind the substance UX111 for Sanfilippo Syndrome Type A, faced controversy during FDA approval and had its application rejected on July 11. The company plans to resubmit an approval application and anticipates another six-month review period for UX111.

Replimune's advanced melanoma drug, RP1, was also rejected by the FDA. In this case, Richard Pazdur, director of the FDA's Oncology Center of Excellence, allegedly intervened to issue the rejection. Replimune's CEO, Sushil Patel, expressed surprise with the decision but remains optimistic about the potential benefits of RP1 in combination with nivolumab for advanced melanoma patients.

Capricor Therapeutics, another company affected by the FDA's changes, has expressed surprise at the rejection of its cell therapy deramiocel. The rejection led to the allegedly forced administrative leave of Nicole Verdun, former director of the FDA's Office of Therapeutic Products, and her deputy, Rachael Anatol. However, Capricor's CEO, Linda Marbán, expressed optimism about fighting the rejection following Vinay Prasad's return to his role at CBER.

Krystal Biotech, discontinued a Phase I/II study of its investigational intratumoral therapy KB707, citing heightened uncertainty regarding potential accelerated approval pathways following the FDA's rejection of RP1. This decision reflects the wider uncertainty facing biopharma companies in the wake of the FDA's new approach.

In response to the FDA's rejection of RP1, 22 experts who designed and ran RP1's Phase III trial issued an open letter, urging the FDA to "re-review" Replimune's application. The letter addressed several issues outlined in the rejection letter, highlighting the potential benefits of RP1 for advanced melanoma patients.

In conclusion, the FDA's new approach to COVID-19 vaccines and drug approvals has brought about a time of change for biopharma companies. The new policies aim to expedite rare disease therapies and speed up drug reviews but have resulted in uncertainty and rejections for several companies. The industry awaits the outcomes of resubmitted applications and the FDA's decisions moving forward.