Only a small fraction of promising peptides ever become approved medicines. Development typically takes ten years or more and costs hundreds of millions of pounds. This is the path every licensed medicine has to follow.
1. Discovery
Researchers identify a biological target, such as a receptor, enzyme or protein–protein interaction, and look for peptides that act on it. Starting points include natural peptides, display library screening and computational design. Lead candidates are then optimised for potency, selectivity and stability through many rounds of synthesis and testing.
2. Preclinical research
Before anyone receives a candidate, it's studied extensively in the laboratory:
- In vitro studies in cells and tissues establish how it works and how potent it is.
- Pharmacokinetic studies measure how it's absorbed, distributed, broken down and cleared.
- Toxicology studies, carried out under Good Laboratory Practice (GLP) standards, look for harmful effects.
- Manufacturing must be developed under Good Manufacturing Practice (GMP), with validated analytical methods for identity, purity, potency and sterility.
3. Clinical trial authorisation
In the UK, a sponsor must apply to the Medicines and Healthcare products Regulatory Agency (MHRA) and receive a favourable opinion from a research ethics committee before a trial can begin. Other countries have equivalent processes, such as an Investigational New Drug application in the US.
4. Clinical trial phases
| Phase | Typical participants | Main question |
|---|---|---|
| Phase I | Tens, often healthy volunteers | Is it safe? How does the body handle it? |
| Phase II | Around a hundred to several hundred patients | Does it work, and at what dose? |
| Phase III | Hundreds to thousands of patients | Does it work better than, or as well as, existing options? What are the less common side effects? |
Most candidates fail somewhere along this path, most often in Phase II because they don't work well enough or show safety problems. By common estimates, roughly one in ten candidates that enter Phase I eventually gains approval.
5. Marketing authorisation
If the evidence is strong enough, the company submits a full dossier to regulators: the MHRA in the UK, the European Medicines Agency in the EU, or the FDA in the US. Regulators assess quality, safety and efficacy before granting a licence, and they define exactly how the medicine may be marketed and used.
6. After approval
Monitoring continues once a medicine is on the market. In the UK, healthcare professionals and the public can report suspected side effects through the Yellow Card scheme. Rare problems sometimes only appear once many thousands of people are using a medicine.
Why this matters: a molecule can look remarkable in cell or animal studies and still fail in people. Approval means the full evidence base and manufacturing quality have been independently assessed. That's the difference between a research compound and a medicine.
Related articles
- Antimicrobial peptides: an ancient defence against modern superbugs
- Cyclic peptides in nature
- Display technologies: searching billions of peptides at once
Sources and further reading
- Wong CH, Siah KW, Lo AW. Estimation of clinical trial success rates and related parameters. Biostatistics 2019;20:273–286. doi:10.1093/biostatistics/kxx069 · PMID: 29394327
- MHRA. Clinical trials for medicines: apply for authorisation in the UK. www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-authorisation-in-the-uk
- MHRA Yellow Card scheme. yellowcard.mhra.gov.uk
- Muttenthaler M, King GF, Adams DJ, Alewood PF. Trends in peptide drug discovery. Nat Rev Drug Discov 2021;20:309–325. doi:10.1038/s41573-020-00135-8 · PMID: 33536635