Lilly weakens on data reveal for oral obesity candidate
Shares in Eli Lilly were tracking down this morning after the company revealed data on its oral weight-loss candidate, orforglipron, that seems to have once again disappointed investors.
The results come from the ATTAIN-1 study, which was teased earlier this year, but has now been presented in full at the EASD congress and simultaneously published in the New England Journal of Medicine (NEJM).
The data in non-diabetic subjects with obesity (a body mass index of 30 or more) reveal that patients on a 6 mg daily dose of the GLP-1 agonist lost an average of 7.5% of their body weight after 72 weeks, rising to 9.3% with a 12 mg dose and 12.4% with 36 mg. The placebo group saw a 0.9% fall.
Lilly's shares fell sharply when the result was first revealed last month, in part because analysts had been hoping for a reduction in the area of 15%.
There was a fresh 1.5% dip in the stock in pre-market trading today that seems to stem from signs that the fall in weight was plateauing towards the end of the study period, as well as a sense that the data is not quite as strong as that seen with Novo Nordisk's 36 mg oral formulation of its rival GLP-1 drug semaglutide, which came in closer to the 15% weight-loss target in trials.
Lilly has pointed to the totality of the data, including that around a fifth of patients taking the drug were able to lose 20% or more of their body weight, as well as positive effects of orforglipron on cardiometabolic risk factors, including non-HDL cholesterol, triglycerides, and blood pressure.
Lilly chief executive David Ricks said recently that while orforglipron may not have the same efficacy as current injectable weight-loss therapies, it has the advantage of more convenient dosing that could unlock greater use in primary care, the ability to be manufactured at a large scale, and efficacy that is "competitive" with other drugs.
The authors of the NEJM paper reach a similar conclusion, writing that the drug "could mean an expansion of obesity interventions to groups who are currently excluded due to the cost of and lack of access to injectable medications."
Lilly said it is preparing to file orforglipron for approval, likely before the end of the year for obesity, with a follow-up filing in type 2 diabetes anticipated in 2026. A regulatory decision on Novo Nordisk's oral formulation of semaglutide for adults who are overweight or living with obesity and cardiovascular disease is due around the turn of the year.
Lead ATTAIN-1 investigator Sean Wharton of the Wharton Medical Clinic, who presented the data at EASD, said: "Obesity is a complex, global health challenge – and patients need treatment options that are both effective and easy to integrate into everyday life. In this Phase 3 study, orforglipron demonstrated strong efficacy results and safety consistent with the GLP-1 class, reinforcing its potential as a first-line treatment in primary care."
Orforglipron bests Rybelsus in diabetes study
Meanwhile, Lilly has also reported top-line data from a head-to-head trial pitting orforglipron against Novo Nordisk's already approved, lower-dose formulation of oral semaglutide – Rybelsus (7mg and 14mg semaglutide) – in adults with type 2 diabetes inadequately controlled with metformin.
In the 52-week ACHIEVE-3 trial, orforglipron was better than Rybelsus at achieving glucose control measured using the HbA1c biomarker, which was lowered by 2.2% and 1,4%, respectively, at the highest doses of the two drugs. At the same time, weight was reduced by 9.2% with orforglipron versus 5.3% with Rybelsus 14mg.
