Taspoglutide

also known as: BIM51077, R1583, RO5073031

A once-weekly GLP-1 RA co-developed by Ipsen and Roche — Phase 3 halted in 2010 after unacceptably high rates of injection-site reactions and hypersensitivity (including systemic allergic reactions), making it the most prominent immunogenicity-driven failure in the GLP-1 class.

A once-weekly GLP-1 receptor agonist (98% homology with native GLP-1, Aib8/Aib35 for DPP-4 resistance) developed by Ipsen and licensed to Roche in 2006; Phase 3 T-EMERGE program was suspended in September 2010 after unacceptably high rates of injection-site reactions, nausea/vomiting leading to discontinuation, and systemic hypersensitivity reactions, and development was formally terminated in 2011 — the archetypal cautionary tale for GLP-1 formulation-driven immunogenicity.

Mechanism of action

GLP-1 receptor agonism. The two Aib substitutions conferred DPP-4 resistance, and a zinc-based depot formulation produced once-weekly pharmacokinetics. The failure mode was immunogenic: antibody formation — possibly accelerated by the zinc-depot formulation — produced both injection-site reactions and, in a subset, systemic hypersensitivity.

Primary uses

Historical: type 2 diabetes mellitus (Phase 3)

Typical dosing

10–20 mg once weekly (subcutaneous)

Phase 3 arms were 10 mg and 20 mg once weekly.

Regulatory status

Not approved. Phase 3 T-EMERGE program halted September 2010; development formally terminated 2011. Roche returned rights to Ipsen.

References

[pubmed] Rosenstock J, et al. "Efficacy and safety of taspoglutide versus sitagliptin for T2DM (T-EMERGE 4)." Diabetes Metab Res Rev, 2013;29:142-151.
[pubmed] Kapitza C, et al. "The effect of the once-weekly glucagon-like peptide-1 receptor agonist taspoglutide on postprandial glycemia." Diabetes Obes Metab, 2009;11:929-936.
[manufacturer] Roche. Media release: discontinuation of T-EMERGE Phase 3 program, September 2010.

Related peptides

Exenatide

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

Liraglutide

The first once-daily GLP-1 analog to be FDA-approved for both type 2 diabetes (Victoza) and chronic weight management (Saxenda).

Dulaglutide

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

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.