Eli Lilly’s new ACHIEVE-4 results may help address some of the FDA’s recent safety questions about Foundayo, the company’s once-daily oral GLP-1 drug also known as orforglipron. After approving Foundayo for obesity earlier this month, the FDA asked Lilly to provide additional data on potential major adverse cardiovascular events (MACE) and drug-induced liver injury, with ACHIEVE-4 identified as a key source for that information.

In today’s release, Lilly said ACHIEVE-4 met its primary objective by showing non-inferior cardiovascular risk versus insulin glargine in adults with type 2 diabetes and obesity or overweight who were at increased cardiovascular risk. The company reported a 16% lower observed risk of MACE-4 events and said its analysis found no hepatic safety signal, consistent with earlier studies in the ACHIEVE and ATTAIN programs.

Lilly also reported stronger A1C and body weight results than insulin glargine at 52 weeks, with those benefits persisting through 104 weeks. In a pre-planned analysis, the company reported a 57% lower observed risk of all-cause death. That result was not controlled for multiplicity, meaning it was not adjusted for the higher chance of a positive finding appearing by chance across multiple analyses, and it should be interpreted with appropriate caution.

The ACHIEVE-4 results appear to directly address two of the FDA’s main post-approval safety concerns: cardiovascular risk and liver safety. They do not address every issue raised in the approval letter, which also called for additional work related to delayed gastric emptying and lactation exposure.

Lilly said it now plans to submit Foundayo to the FDA for type 2 diabetes by the end of the second quarter.

Sources

Eli Lilly Press Release
Fierce Pharma: FDA tells Eli Lilly to round up more safety info on key obesity launch Foundayo
Fierce Pharma: Lilly answers FDA's call for more Foundayo safety info, plotting diabetes filing in parallel