Lilly says Foundayo safety confirmed in ACHIEVE-4 trial
Eli Lilly says it has the safety data it needs to shore up the recent speedy approval of its oral obesity therapy Foundayo, and also to file the GLP-1 agonist for approval in type 2 diabetes later this quarter.
The results of the 2,700-patient ACHIEVE-4 trial have been highly anticipated since the FDA said it would need to see evidence of the safety of Foundayo (orforglipron) – specifically on liver and cardiovascular side effects – as a condition of the FDA's approval of the drug under the national priority review voucher programme.
Lilly said it will also seek a national priority review of the drug in diabetes, giving it a chance of leapfrogging first-to-market oral GLP-1 drug, Novo Nordisk's Wegovy (semaglutide) pill, in that indication.
ACHIEVE-4 compared Foundayo to insulin glargine in patients with type 2 diabetes and overweight or obese who are at elevated cardiovascular risk, and met the primary objective of non-inferiority to the control with a reduction in the risk of major adverse cardiovascular events (MACE).
Specifically, there was a 16% lower risk of MACE-4 events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for unstable angina or heart failure), and a 23% lower risk of MACE-3 (cardiovascular death and nonfatal MI and stroke).
Moreover, Foundayo-treated patients also had a 57% reduced risk of all-cause death than the insulin glargine group, which Lilly said points to "more comprehensive health benefits" with the GLP-1 drug, alongside "superior improvements" in glucose control and body weight out to 104 weeks of follow-up.
Crucially, the study showed no signs of drug-induced liver injury (DILI), meeting the FDA's other main safety concern, which Lilly said was in line with its other trials of Foundayo. There was a 10.6% rate of treatment discontinuation in the first year of treatment, mainly due to gastrointestinal side effects like nausea, vomiting, diarrhoea, and constipation.
"Across seven phase 3 studies enrolling more than 11,000 patients, Foundayo has demonstrated a consistent safety and efficacy profile," said Thomas Seck, head of cardiometabolic product development at Lilly.
"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."
As well as reinforcing the cardiovascular safety of Foundayo, the ACHIEVE-4 data – if added to Foundayo's labelling – could help counteract one advantage cited by Novo Nordisk for Wegovy, namely that it has cardiovascular risk reduction on its label (albeit for the injectable version of the drug).
Novo Nordisk and Lilly are now battling toe-to-toe in the US market for oral GLP-1 drugs for weight-loss, continuing a marketing tussle in the injectable category that of late has seen Lilly in the ascendancy.
Lilly is highlighting that Foundayo can be taken any time of day, without food or water restrictions, while Wegovy has to be taken first thing in the morning on an empty stomach, half an hour before eating or drinking. Novo Nordisk, meanwhile, is claiming greater efficacy in reducing weight and notes that Foundayo has its own restriction, in that it should not be taken alongside oral birth control or the widely used cholesterol-lowering drug simvastatin.
Ultimately, the contest could come down to commercial reach and marketing muscle, and both Lilly and Novo Nordisk have been working hard to develop a network of third-party providers, targeting both individuals and company health plans, along with aggressive pricing for the oral therapies.
