FDA Scientists Raise Peptide Concerns Ahead of Committee Meeting

Undercutting HHS Secretary Robert F. Kennedy Jr.’s recent push to expand access to peptides, FDA career scientists determined there isn’t adequate evidence to support any of the ones under consideration for production by compounding pharmacies.

Upcoming Meeting

At an upcoming meeting of FDA’s Pharmacy Compounding Advisory Committee (PCAC) on July 23 and 24, the free base and acetate peptides that will be discussed are:

• BPC-157 (15 amino acids) for ulcerative colitis
• KPV (3 amino acids) for wound healing and inflammatory conditions
• TB-500 (7 amino acids) for wound healing
• MOTS-c (16 amino acids) for obesity and osteoporosis
• Emideltide (9 amino acids) for opioid withdrawal, chronic insomnia, and narcolepsy
• Semax (7 amino acids) for cerebral ischemia, migraine, and trigeminal neuralgia
• Epitalon (4 amino acids) for insomnia

Safety and Efficacy Concerns

In the briefing documents, FDA scientists weighed against all of them, noting that all had lacking, flawed, or completely absent information on safety and efficacy in humans. All peptides except TB-500 were described as “not well-characterized from the physical and chemical characterization perspective.” Reviewers noted particular immunogenicity risk for injectable formulations.

Research on Emideltide

Of these peptides, emideltide had the most research. It’s been studied for use in humans since at least 1981, according to the documents, and compounded since 2018. Because of its limited water solubility, it’s unclear how emideltide could be formulated in the proposed injectable dosage. Injection and intranasal products are available in integrative neurology clinics, medical concierge services, medical spas, wellness clinics, and online, though it’s not known if these products are compounded. In studies of intravenous emideltide, subjects with withdrawal symptoms reported side effects like transient headache, nausea, and vertigo, as well as cases of hypotension that were “progressive” following the second injection.

Clinical Research Limitations

While there have been clinical studies on emideltide for treating chronic insomnia, these have been inconclusive and preliminary at best, with flawed methodologies and small sample sizes, the briefing materials noted. Studies for treating narcolepsy and opioid withdrawal were also limited. Pharmacologically, emideltide has sleep-inducing properties through opioid-dependent mechanisms.

“Although emideltide does not appear to interact directly with opioid receptors, it can stimulate calcium-dependent release of endorphins,” FDA staff wrote. This could potentially suppress alcohol/opioid withdrawal symptoms, but could lead to addiction, and there’s no research on this potential addictive potential, they added.

Semax and Other Peptides

Semax exhibits pleiotropism and is widely marketed in wellness, functional, and regenerative medicine clinics. The briefing documents stated it’s a registered drug in Russia, available as 0.1% and 1% nasal drops. Research in mice has suggested it has neuroprotective, neurotrophic, anticoagulant, antithrombotic, and analgesic properties, as well as antidepressant and anxiolytic effects. However, semax also potentiated amphetamine-induced dopamine release in the striatum, which is typically induced by drugs of abuse like cocaine, and there is no research on its abuse potential or other safety considerations.

BPC-157 has limited research and was first described in the literature in 1993. It has primarily been mentioned concerning gastrointestinal uses. There’s a single exploratory trial evaluating it for ulcerative colitis, and some smaller trials testing administration via rectal enema. Its mechanism of action is not well understood, and no research has been done on the proposed routes of administration. Reviewers also noted strong concerns about the nasal spray version of BPC-157 and semax due to a lack of information about the container closure system.

Information on epitalon suggests it has been used in compounding since 2018, but there’s a lack of studies evaluating it for treating insomnia, particularly via the proposed subcutaneous route. Pharmacologically, epitalon can increase serum levels of melatonin, potentially influencing sleepiness, though no studies assess electroencephalographic endpoints. Additionally, epitalon has the potential to be carcinogenic.

There is a complete lack of studies in humans regarding KPV, MOTS-c, and TB-500. Scientists noted a lack of information on the proposed creams and gels of KPV, leaving them unable to evaluate characteristics. For MOTS-c, which is marketed for various uses, there has been some research in vitro and in rodent models, but lack of dose-response assessments limits application. Interest in TB-500 has surged since 2010, but it’s uncertain if products sold online are compounded. An in vitro study found that TB-500 free base didn’t induce wound healing.

FDA’s Position

FDA staff repeatedly noted that many of the conditions the peptides are purported to treat already have existing FDA-approved therapies. Peptides are chains of amino acids that are growing in popularity, particularly within the wellness community. They are often marketed as having anti-aging and health benefits, albeit not backed by clinical trials like FDA-approved drugs.

Earlier this month, members of the American Medical Association House of Delegates called for more regulation of unproven peptides, while back in 2024, the Alliance for Pharmacy Compounding deemed some too risky for compounding due to safety concerns.

Meanwhile, Secretary Kennedy expressed his support for peptides on a podcast earlier this year. He recently added new members to PCAC, several of whom have peptide-related business ventures, raising concerns about conflicts of interest.

FDA doesn’t have to heed the advice of its advisory committees, but it usually does.

Disclaimer: This article is for informational purposes only and should not be considered medical advice. Always consult a healthcare professional for medical concerns or before starting any new treatment.

Fuente: https://www.medpagetoday.com/publichealthpolicy/fdageneral/122018