FDA committee votes to make peptides more widely available

Peptide enthusiasts—including Health and Human Services Secretary Robert F. Kennedy Jr.—might soon be able to buy the controversial products more easily from regulated sources. The short chains of amino acids, touted as treatments for joint health, wound recovery, insomnia, and many other conditions in a burgeoning multibillion-dollar gray market, were the subject of a highly anticipated meeting of independent advisers convened by the U.S. Food and Drug Administration (FDA) that started yesterday. In the first half of the 2-day meeting, the committee voted narrowly to recommend that the agency allow specialized pharmacies to formulate four specific peptides. The committee will vote on three more peptides today. The peptides, which are only allowed to be made and sold for research purposes, currently fall into a legal gray area. FDA scientists were not in favor of expanding access to the substances. In documents submitted ahead of this week’s committee meeting, they argued there is too little clinical data to support the peptides’ efficacy and that they carry unknown health risks. But proponents of peptides argue that approved compounding pharmacies, which formulate raw materials into usable forms such as injectable drugs, should be allowed to produce them in sterile environments and sell them directly to consumers. That would help protect the public from inexpertly produced or potentially contaminated products from less reputable sources, they argued. The committee, which includes at least seven people involved in companies selling peptides, narrowly voted in favor of allowing compounding. Here’s what to know about the molecules the committee considered, and the implications of a possible regulatory change. What peptides are being discussed, and what do we know about them? This week’s meeting addresses seven specific peptides: BPC-157 for connective tissue repair and gastrointestinal conditions, KPV and TB-500 for wound healing, MOTS-c for metabolism and other uses, Emideltide for opioid withdrawal and sleep disorders, Semax for cognitive disorders, and Epitalon for insomnia. BPC-157 and several of the other peptides mimic molecules naturally produced by the human body. In submitted dossiers compiling the data on each, FDA scientists say there’s too little evidence to conclude any of the peptides are either safe or effective. Few have undergone the rigorous clinical testing FDA normally requires to approve a drug, and the agency scientists said the peptide trials conducted to date have not proved efficacy. “In order for us [as health care providers] to be safely supporting and recommending these, they have to have really good research and education on them,” says Brigid Groves, a pharmacist and vice president of professional affairs at the American Pharmacists Association. Her organization submitted a public comment recommending against allowing compounding, given the lack of data. What was the committee asked to decide? In 2023, FDA added the seven peptides being voted on and 12 others to a list of products that it deems too dangerous for compounding pharmacies to make. But in April, FDA withdrew the seven peptides and several others from the high-risk list in a move Kennedy said would “immediately begin shifting demand away from the black market.” Now, FDA is considering going further by adding the seven to a separate category known as the 503A Bulks List. This would allow any compounding pharmacy that adheres to good manufacturing standards to produce the peptides and sell them directly to consumers. What are the risks of the peptides? According to the FDA scientists, these peptides have a high risk of triggering the immune system to overreact and cause anaphylaxis or other symptoms. Researchers typically make such determinations by studying the sequence of amino acids that make up the peptide and how similar it is to other compounds with known risks. This and other types of studies can predict, for example, whether the molecules are likely to clump together and form a giant peptide that the body recognizes as a foreign invader. But FDA determined there was not enough data to assess the likelihood of such harm in these peptides. Synthetic peptides mimicking molecules that occur naturally in the body also risk prompting a lasting immune response, says Annie de Groot, president of the biotech startup EVA Therapeutics. This has been a problem in the past with compounds such as synthetic erythropoietin, a hormone that drives red blood cell production. “You’re taking a risk for a drug with unknown efficacy by using compounded drugs,” she says. There is also little data on whether the seven peptides under consideration are safe for people with various health conditions, whether they have harmful interactions with other drugs, and whether they act differently depending on whether they are injected or taken orally or through a nasal spray. What risks arise during the manufacturing process? FDA experts concluded in the 2023 decision that the peptides are difficult to manufacture safely and the processes carry significant risks. Several of the peptides on the list, for instance, don’t dissolve well in water and can easily come out of solution, meaning a person injecting one of them might receive a different dose each time. The peptide manufacturing process can also introduce impurities if the wrong amino acids are incorporated into the product. De Groot points to a 2013 case in which an experimental peptide called taspoglutide caused anaphylaxis symptoms in people taking it during a phase 3 clinical trial for diabetes. Researchers later found that the manufacturing process may have caused errors in the peptide’s amino acid sequence. (Taspoglutide was a glucagonlike peptide-1 agonist, the same class of peptides that have become wildly popular diabetes and obesity drugs. Those drugs, unlike the peptides being voted on this week, went through clinical tests in many thousands of people.) Are there potential benefits to adding these peptides to the Bulk List? This form of regulation could have some advantages over the current state of affairs, Groves says. Buyers can be sure the peptides were produced in a sterile environment and the substance they buy is actually the correct one. Production in approved pharmacies would also make it easier to monitor any harmful side effects or other problems, because these facilities must keep track of where they sourced their raw materials. What will FDA do now? FDA isn’t obligated to follow the recommendations of its advisory committees. At the meeting yesterday, an agency official said it will weigh the conflicting recommendations of the committee and agency scientists, alongside new data submitted in public comments ahead of the meeting. It will issue a final decision in the coming weeks.