Five-trial phase 3 program to support regulatory filing in ~2021; Addition of three-dose studies vs. placebo in patients on (i) basal insulin, (ii) metformin +/- SUs
Sanofi has added two additional phase 3 trials to its lineup for once-weekly GLP-1 agonist efpeglenatide, joining three already-recruiting studies. AMPLITUDE-L (n=400) will enroll patients already on basal insulin and AMPLITUDE-S (n=640) patients on background metformin with or without SUs. Both investigate three efpeglenatide doses vs. placebo and are expected to complete April 2021.
These trials join three currently-recruiting phase 3 studies: (i) AMPLITUDE-M, a three-dose study enrolling 400 treatment-naïve participants (expected completion August 2020), (ii) AMPLITUDE-D, a three-dose study vs. dulaglutide enrolling 900 participants on metformin (December 2020) and (iii) AMPLITUDE-O, a 4,000 participant superiority-powered CVOT (April 2021). Phase 3 for efpeglenatide was initiated in 4Q17.
To our understanding, Sanofi still aims to file efpeglenatide in 2021, and we’re glad to see an expanded commitment to the candidate. Given Sanofi’s first GLP-1 agonist Adlyxin (lixisenatide) has struggled to gain commercial traction since launch – and has been heavily deprioritized by the company – it’s positive to see the company reinvest in GLP-1s (with a half-life of ~three hours, Adlyxin is also a relatively ineffective GLP-1). Indeed, Sanofi has already produced its own autoinjector, to be used in AMPLITUDE-D, reflecting the company’s enthusiasm over the candidate.
To be sure, this dedication to efpeglenatide reflects the ever-increasing importance of the GLP-1 agonist class: GLP-1s now comprise more revenue than rapid-acting insulins, and the class is now recommended as the first injectable, before basal insulin. That said, we’ll be looking for Sanofi to bring innovation to the class, as well. Management has previously asserted that GI side effects improve more rapidly with efpeglenatide vs. other GLP-1s, which could bring improved adherence and satisfaction – and, as a result, outcomes. They’ve also shown modeled data projecting equivalent efficacy to Novo Nordisk’s Ozempic. However, we’ve yet to see data supporting this, so it remains to be seen how Sanofi might position efpeglenatide within an increasingly competitive class.
With once-weekly dosing and autoinjection (the Trulicity formula, if you will) in place, a superior clinical profile could make efpeglenatide a big win for Sanofi’s struggling diabetes franchise. One thing is for certain: There remains significant room for GLP-1s to continue expanding, and efpeglenatide could both benefit from and help drive that trend.
-- by Ann Carracher and Kelly Close