Why most peptides are not FDA-approved

Most peptides people run have no FDA approval. The main reason is money. Approval starts when a company files for it, and few companies will fund the trials for a molecule they cannot own.

What FDA approval is

The FDA does not pick compounds and test them. Its drug center says it "doesn't actually test drugs itself." A company, called the sponsor, runs the animal studies and human trials. It then files a New Drug Application asking the agency to approve the drug for sale, and FDA scientists review that file.

So the chain is short. No sponsor means no application, and no application means no approval, whatever the compound does in the research.

What the trials cost

• About $2.6 billion. DiMasi of Tufts and two co-authors (2016) put the average cost of one approved drug at $2,558 million in 2013 dollars. That counts the compounds that failed along the way and the cost of capital. Out-of-pocket spending alone averaged $1,395 million.
• About $1.1 billion. Wouters and colleagues in JAMA (2020, corrected in 2022) worked from public filings on 63 drugs. They found a median of $1,141.7 million in 2018 dollars, failed trials included.

The two teams used different data and different methods. Both land above a billion dollars for each approved drug.

Why native peptides rarely find a sponsor

A sponsor earns that money back through a patent on the molecule itself, called a composition-of-matter patent. A US patent runs 20 years from its filing date, and it keeps every competitor off that molecule.

In 2013 the Supreme Court decided Association for Molecular Pathology v. Myriad Genetics (569 U.S. 576). Myriad had patented two human genes it isolated, BRCA1 and BRCA2. The Court held that "a naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated." Lab-made cDNA stayed eligible because it does not occur in nature.

Myriad was a patent case about DNA. It was not a ruling about the FDA, and no peptide patent was before the Court. The Court also said it was not deciding method patents or altered sequences.

The US Patent and Trademark Office applies the same test to every nature-based product. A nature-based product counts as a product of nature unless it has "markedly different characteristics" from its natural counterpart in structure, function or other properties. A claim to that product alone then fails. One of the office's 2016 examiner examples is a vaccine made of a naturally occurring viral peptide and a carrier, which can be plain water. The claim fails because the peptide "retains its naturally occurring structure and function." In the same example the same peptide coated on a microneedle array passes, because that new kind of device adds "significantly more." A company can claim the peptide on a novel device. It cannot claim the molecule itself.

A copy of a sequence the body already makes runs into that test. What stays open is the narrower protection around the molecule. A company can patent a device, a formulation or a new use, and the FDA grants five years of exclusivity to a new chemical entity and seven to an orphan drug. Each is narrower or shorter than 20 years on the molecule, which is weak protection for a billion-dollar investment.

What did get approved

Look at four peptides that reached approval since 2010. Each carries a change that nature did not make, and a changed molecule is one a company can own.

The details come from each drug's FDA label. This site covers all four at Semaglutide, Tirzepatide, Tesamorelin and PT-141. Muttenthaler and colleagues, writing in Nature Reviews Drug Discovery in 2021, counted more than 80 peptide drugs that have reached the market.

A native sequence can be approved when a sponsor files. Teriparatide (Forteo, approved 2002) has "an identical sequence" to the first 34 amino acids of human parathyroid hormone.

Approval depends on the country

• Thymosin alpha-1 is approved in over 35 countries, according to a 2009 review by Goldstein and Goldstein. It does not appear in the FDA's database of approved drugs.
• Semax and Selank are among 14 peptide drugs registered in Russia, listed as a nootropic and an anxiolytic (Deigin and colleagues, 2022).
• Cerebrolysin is "used clinically in over 50 countries" and is not approved in the USA (Fiani and colleagues, 2021).

What "not FDA-approved" tells you

It tells you that no sponsor has carried the compound through an FDA application. It does not measure the research behind the compound, and it certifies nothing about safety, purity or effect either.

For the research itself, open the peptide's page. Every page lists its references, and where human trials exist the page gives their results.