FDA Panel Finds a Peptide It Doesn't Like

 An FDA panel on Friday continued to recommend loosening compounding restrictions for all but one of the peptides it reviewed, despite safety concerns from agency scientists for all of them.

During the second day of deliberations, the FDA's Pharmacy Compounding Advisory Committee (PCAC) voted to add two out of three peptides in question to the 503A bulk drugs list: epitalon and semax received favorable votes of 7-5 and 8-5 (with one abstention each), respectively, for both free base and acetate versions. Epitalon has been proposed for insomnia, and semax has been proposed for cerebral ischemia, migraine, and trigeminal neuralgia.

Only emideltide received a majority of no votes at 7-6 (with one abstention) for both its free base and acetate versions. Emideltide has been proposed for opioid withdrawal, chronic insomnia, and narcolepsy.

On the first day of the PCAC meeting, a majority on the committee voted in favor of putting the free base and acetate forms of BPC-157, KPV, TB-500, and MOTS-c on the 503A list of substances that can be used in compounding.

Altogether, six of seven peptides were bolstered by the newly appointed PCAC, which includes publicly known peptide promoters and producers among its ranks.

Among them is Republican Tennessee state senator Bobby Harshbarger, PharmD, of Premiere Pharmacy, a family business that sells compounded medications for weight loss, longevity, pain, and other conditions.

"I voted yes because our duty is to apply the 503A standards, not the investigational new drug application standard. Of course, this vote doesn't approve a drug or indication. It permits patient-specific compounding under a valid prescription, not mass production for unidentified consumers or routine copying of commercially available drugs," Harshbarger said on emideltide.

Peptides are trending among wellness influencers, who tout their anti-aging and health benefits despite the lack of a robust evidence base. The peptides are not FDA approved but can be purchased online or via various integrative neurology clinics, medical concierge services, medical spas, and wellness clinics. However, custom-prepared peptide formulations are currently barred from sale, as they are excluded from permitted compounding lists.

HHS Secretary Robert F. Kennedy Jr. has been vocal about his desire to loosen restrictions on the production of some peptides by compounding pharmacies, arguing that the current ban has created a "very dangerous" black market for these compounds.

During the 2-day PCAC meeting, FDA staff scientists maintained that these peptides were chemically "not well characterized" and that few safety or efficacy studies support them for the proposed uses. A potential for immunogenicity (from peptide aggregation and possible impurities) was also flagged for the peptides, with epitalon in particular theoretically having some potential for causing cancer, and semax having possible anti-thrombotic properties.

Agency staff also repeatedly noted that many of the conditions that the peptides are purported to treat already have existing FDA-approved therapies.

In contrast, compounded drugs are not FDA approved, meaning their safety, effectiveness, and quality are not subject to the same scrutiny by regulators. For example, even a drug product legally compounded under Section 503A is not required to have a label with instructions for use. Compounders are not required to comply with current good-manufacturing practices, nor are they obligated to report adverse events to the FDA.

"I think it's about patient access," said PCAC member Asare Christian, MD, MPH, of Aether Medicine, a peptide-offering pain clinic in Philadelphia. Pointing to his yes vote for epitalon, he noted, "As a physician, I'm always quantifying risk ... Even when I give somebody gabapentinoids, which are actually FDA approved, there's all this risk that I have to manage."

Timothy Fensky, RPh, DPh, a liaison from the National Association of Boards of Pharmacy (NABP), abstained from all three votes on Friday and explained that the NABP does not support or oppose the inclusion of any peptide on the 503A bulk drugs list. However, "NABP urges FDA to use the time before any final rule to build an infrastructure or framework with NABP and the state boards of pharmacy ... such as adverse event reporting," Fensky said.

While the FDA is not required to follow the advice of its advisory committees, it typically does.

An additional five peptides will be considered when PCAC reconvenes in early 2027, according to an announcement during Friday's meeting.

https://www.medpagetoday.com/publichealthpolicy/fdageneral/122345