Clinical Trials Pipeline & In-Development

Efpeglenatide

also known as: HM11260C, LAPSCA-Exendin-4, SAR439977

A weekly-to-monthly exendin-4-based GLP-1 agonist with positive Phase 3 cardiovascular outcomes (AMPLITUDE-O, 2021) — Sanofi returned the license to Hanmi in 2020; Hanmi re-partnered with Innovent in 2020 for China development and with Kailera in 2024 for global development.

A long-acting exendin-4 analog built on Hanmi Pharmaceutical's LAPSCOVERY (Long-Acting Protein/Peptide Discovery) platform, which conjugates exendin-4 to an IgG4 Fc fragment via a non-peptidyl flexible linker, producing weekly-to-monthly dosing; AMPLITUDE-O (2021) demonstrated a 27% reduction in MACE in high-CV-risk type 2 diabetes — among the largest GLP-1 CV-outcome benefits reported — but Sanofi returned global rights to Hanmi in 2020 citing strategic-portfolio reasons.

Mechanism of action

GLP-1 receptor agonism via a long-acting exendin-4 scaffold. The IgG4 Fc conjugation provides FcRn-mediated recycling that dramatically extends plasma half-life beyond native exenatide (~2.4 h) to support weekly-to-monthly administration. Mechanistically identical to other GLP-1 RAs: glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, central appetite suppression.

Primary uses

Type 2 diabetes mellitus with cardiovascular risk (Phase 3)
Obesity (in development)

Typical dosing

4–6 mg once weekly (subcutaneous)

Phase 3 AMPLITUDE-O used 4 mg and 6 mg weekly dose arms. Monthly schedules explored in earlier studies.

Regulatory status

Not approved. Phase 3 AMPLITUDE-O completed 2021 with positive CV outcomes; Sanofi returned global rights to Hanmi Pharmaceutical in 2020. Hanmi licensed Greater China rights to Innovent Biologics in 2020 and global ex-China rights to Kailera Therapeutics in 2024 for further development in obesity and T2DM.

References

[pubmed] Gerstein HC, et al. "Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes (AMPLITUDE-O)." N Engl J Med, 2021;385:896-907.
[manufacturer] Hanmi Pharmaceutical. Announcement: efpeglenatide global licensing agreement with Kailera Therapeutics, 2024.
[clinicaltrials] ClinicalTrials.gov NCT03496298 (AMPLITUDE-O): Effect of Efpeglenatide on Cardiovascular Outcomes.

Related peptides

Exenatide

The first GLP-1 receptor agonist to reach market (2005), available in both twice-daily and weekly extended-release formulations.

Dulaglutide

A weekly GLP-1 agonist for type 2 diabetes, delivered as a GLP-1/IgG4 fusion protein in a single-use auto-injector.

Semaglutide

A once-weekly GLP-1 receptor agonist FDA-approved for type 2 diabetes and chronic weight management.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.