Lilly's Foundayo weight loss pill clears heart safety bar in largest diabetes trial yet

Eli Lilly $LLY's oral weight loss pill Foundayo demonstrated a non-inferior risk of major cardiovascular events compared with insulin glargine in the largest Phase 3 diabetes trial of the drug to date, the company said April 16, paving the way for an FDA filing to expand its approved uses to include type 2 diabetes.

A total of 2,749 people in 15 countries were randomized into the ACHIEVE-4 trial. Measured against insulin glargine, Foundayo was associated with a hazard ratio of 0.84 (95% CI: 0.59 to 1.20) for the composite endpoint of cardiovascular death, heart attack, stroke, or hospitalization for unstable chest pain — a 16% relative reduction. That result met the trial's prespecified non-inferiority threshold. Mortality from any cause was also examined in a pre-planned analysis, with Foundayo showing a 57% relative reduction versus insulin glargine (hazard ratio: 0.43; 95% CI: 0.25 to 0.75); Lilly noted the finding was not adjusted for multiplicity.

After 52 weeks, patients taking Foundayo had better blood sugar control and lost more weight than those on insulin glargine. The Foundayo group saw their A1C drop by an average of 1.6 percentage points, compared to a 1.0-point drop with insulin glargine. On average, Foundayo patients lost about 17.9 pounds (an 8.8% decrease), while those on insulin glargine gained about 3.1 pounds (a 1.7% increase).

"Across seven Phase 3 studies enrolling more than 11,000 patients, Foundayo has demonstrated a consistent safety and efficacy profile," Thomas Seck, senior vice president of product development at Lilly Cardiometabolic Health, said in a statement. "ACHIEVE-4 adds a new dimension to that evidence — cardiovascular safety and a lower observed risk of all-cause death in patients who carry elevated cardiovascular risk."

Lilly reported that the trial’s safety results matched those from earlier Foundayo studies and were similar to other GLP-1 drugs. The most common side effects were nausea, vomiting, diarrhea, decreased appetite, and constipation. About 10.6% of Foundayo patients stopped treatment due to side effects during the 52-week trial. A specific analysis for drug-induced liver injury found no liver safety issues.

An FDA submission seeking a type 2 diabetes indication for Foundayo is planned before the close of Q2, Lilly said, to be filed under the Commissioner's National Priority Review Voucher program. According to Bloomberg, the FDA had required Lilly to submit cardiovascular and liver safety data from the trial by July as a condition tied to the drug's approval.

Foundayo received FDA approval for chronic weight management just weeks before the ACHIEVE-4 results were announced, making it the only GLP-1 pill that can be taken at any time of day without restrictions on food or water. Lilly set cash-pay pricing on a sliding scale between $149 and $349 per month, with a manufacturer coupon available that may reduce the cost to $25 per month for commercially insured patients. The drug competes directly with Novo Nordisk's oral weight loss pill.

The compound behind Foundayo is a non-peptide, small molecule GLP-1 receptor agonist dosed once daily; Chugai Pharmaceutical originally developed it before Lilly acquired the license in 2018. Active research programs are also exploring Foundayo's utility in obstructive sleep apnea, osteoarthritis knee pain, hypertension, peripheral artery disease, and stress urinary incontinence, beyond its existing weight management indication and the pending diabetes use.