Even as Eli Lilly embarks on the launch of its next big obesity drug with Foundayo, FDA documents regarding the oral treatment indicate that concerns remain about multiple “unanticipated and serious” risks potentially associated with the drug.
In the FDA’s approval letter (PDF) for the GLP-1 pill Foundayo, the agency ordered Eli Lilly to obtain more information about the drug’s potential association with serious cardiovascular events and drug-induced liver damage. Additionally, the agency would like to learn more about the delayed gastric emptying associated with this drug and its potential effects in breastfeeding women.
In evaluating the drug data, the FDA “determined that clinical trials alone (rather than non-clinical or observational studies) are sufficient to assess serious risk signals from gastric retention and to identify unexpected and serious risks for serious cardiovascular events (MACE), drug-induced liver injury (DILI), and exposure to (Faundayo) during breastfeeding,” the letter said.
Based on the findings, the agency hopes Eli Lilly will complete the Achieve-4 study as planned and “provide additional safety data” on the potential for MACE and DILI, according to Foundayo’s approval letter.
The trial will test the drug, also known as orforglipron, against insulin glargine in patients with type 2 diabetes and obese or overweight patients at high cardiovascular risk. In the drug’s approval, the FDA said it required Lilly to submit a clinical study report detailing any major cardiac or liver safety events recorded during the trial.
The agency also proposed several other postmarket requirements in its April 1 letter. These include clinical pharmacology studies to measure the effects of orforglipron discontinuation and fasting, as well as potential effects related to delayed gastric emptying. This is part of an effort to “inform potential recommendations to reduce the significant risk of pulmonary aspiration,” the agency said.
The agency also calls for conducting “a breast-exclusive lactation study to evaluate the concentration of orforglypron in breast milk using a validated analytical method in lactating women receiving orforglypron.”
Lilly’s Foundayo has received the FDA’s green light under the agency’s controversial new Commissioner’s National Priority Voucher Program. The program aims to expedite the approval of medicines that are deemed to meet one or more of the agency’s set of national interests.
The GLP-1 pill is competing in the market with Novo’s similarly new pill Wegovy, which received FDA approval in January.
In clinical trials, treatment with Foundayo resulted in an average weight loss of 12.4% in patients who adhered to the treatment regimen. Another trial of Novo’s Wegovy tablets showed an average weight loss of 16.6%, but comparisons between trials have inherent flaws.
Among the potential benefits for Foundayo, Lilly noted that the company’s drug is the only GLP-1 pill that can be taken at any time of the day without food or water restrictions. Novo’s Wegovy tablets should be taken on an empty stomach in the morning with up to 4 ounces of water. Do not take any other liquids.
