FDA cleared Foundayo, Eli Lilly’s oral GLP-1 pill for obesity, on April 1, but the approval letter lists three postmarketing requirements tied to what the agency calls “unexpected serious” risks potentially linked to the drug.
The FDA wants Lilly to complete its Achieve-4 clinical trial and submit safety data on major adverse cardiovascular events (MACE) and drug-induced liver injury (DILI). The agency was direct: only a clinical trial will suffice to assess these signals, ruling out nonclinical or observational study designs.
Two other requirements followed. A clinical pharmacology trial must measure the effects of withholding orforglipron while fasting, aimed at informing recommendations to mitigate “the serious risk of pulmonary aspiration” from delayed gastric emptying. Lilly also needs to run a milk-only lactation study in lactating women dosed with orforglipron to measure breast milk concentrations.
Foundayo got its nod under the FDA’s Commissioner’s National Priority Voucher program. It’s now competing against Novo Nordisk’s Wegovy pill, which cleared in January. In a clinical trial, Foundayo delivered average weight loss of 12.4% in adherent patients. Novo’s Wegovy pill showed 16.6%, though cross-trial comparisons carry inherent flaws.
Lilly’s edge: Foundayo can be taken at any time without food or water restrictions. Novo’s Wegovy pill doesn’t offer that flexibility: morning dosing, empty stomach, no more than 4 ounces of water.
The Achieve-4 trial is testing orforglipron against insulin glargine in Type 2 diabetes patients with obesity or overweight at elevated cardiovascular risk. A clinical study report covering cardiac and liver safety events is a condition of the April 1 approval.
— Sarah Chen