Even as Eli Lilly gets underway with its next major obesity launch in Foundayo, an FDA document related to the oral treatment shows lingering reservations about multiple “unexpected serious” risks potentially related to the drug.
In the FDA’s approval letter (PDF) for GLP-1 pill Foundayo, the agency tasks Eli Lilly with obtaining more information about the med’s potential link to major adverse cardiovascular events and drug-induced liver injury. In addition, the agency wants to gain more info about delayed gastric emptying associated with the drug and its potential effects in lactating women.
In its assessment of the medicine’s data, the FDA “determined that only a clinical trial (rather than a nonclinical or observational study) will be sufficient to assess a signal of a serious risk of retained gastric contents and to identify an unexpected serious risk for major adverse cardiovascular events (MACE), drug-induced liver injury (DILI), and exposure to [Foundayo] during lactation,” the letter says.
Based on this finding, the agency said it wants Eli Lilly to complete its Achieve-4 study, as planned, and “provide additional safety data” related to MACE and the potential for DILI, the Foundayo approval letter shows.
The trial is testing the drug, also known as orforglipron, against insulin glargine in patients with Type 2 diabetes and obesity or overweight who are at an increased cardiovascular risk. In the drug’s approval letter, the FDA says it wants Lilly to submit a clinical study report detailing any major cardio or liver safety events recorded during the trial.
The agency also put forward a couple of other postmarketing requirements in the April 1 letter. Those include a clinical pharmacology trial to measure the effects of withholding dosing of orforglipron and fasting and potential implications related to delayed gastric emptying. This is part of a bid to “inform potential recommendations to mitigate the serious risk of pulmonary aspiration,” the agency said.
Further, the agency wants the company to conduct a “milk-only lactation study in lactating women who have received a dose of orforglipron to assess concentrations of orforglipron in breast milk using a validated assay.”
Lilly’s Foundayo won the FDA’s green light under the agency’s controversial new Commissioner’s National Priority Voucher program, which seeks to speed approvals for medicines deemed to meet one or more of a set of national interests laid out by the agency.
The GLP-1 pill is facing off in the market against Novo’s similarly new Wegovy pill, which landed its FDA nod back in January.
In a clinical trial, treatment with Foundayo yielded an average weight loss of 12.4% among patients who adhered to their treatment regimens. A separate trial of Novo’s Wegovy pill showed average weight loss of 16.6%, though cross-trial comparisons carry inherent flaws.
In one potential edge for Foundayo, Lilly has pointed out that its med is the only GLP-1 pill that can be taken whenever during the day without any food or water restrictions. Novo’s Wegovy pill must be taken on an empty stomach in the morning with up to 4 ounces of water—not any other liquids.
