Lilly weakens on oral weight-loss drug data

Shares in Eli Lilly have come under pressure after reporting the results of a phase 3 trial of oral weight-loss candidate orforglipron, suggesting the outcome has not impressed investors.

The oral GLP-1 agonist achieved a reduction in weight of up to 12.4% at 72 weeks in the phase 3 ATTAIN-1 study – an average of around 12.4kg – in non-diabetic adults with obesity or overweight and a weight-related medical problem.

The best weight-loss result was achieved with a 36mg dose of the drug, with the placebo group achieving a reduction of 0.9%. A lower 12mg dose achieved a reduction of 9.3%, with patients in the lowest 6mg dose arm seeing a 7.8% reduction.

Some analysts had been hoping for a reduction in the area of 15% with the drug, and Lilly chief executive David Ricks accepted in an interview with CNBC that the readout was "one to two points below" expectations.

The result is strong enough to plan regulatory filings for orforglipron, said Lilly, but the sell-off in its shares – down more than 2.5% at the time of writing – suggests there are concerns that the profile of the drug is not as compelling as hoped, as rival oral GLP-1-acting drugs advance through the industry pipeline as alternatives to the current injectable products.

In particular, there was a fairly high rate of treatment withdrawal due to side effects of around 10% in the high-dose group, though on the plus side there was no sign of the liver toxicity that scuppered rival oral GLP-1 candidates from Pfizer.

For comparison, Lilly's arch-rival in the weight-loss category, Novo Nordisk, is developing an oral formulation of GLP-1/amylin agonist amycretin that achieved reductions of between 10.4% and 13.1% in a phase 1 trial, compared to a fall of 1.2% in the placebo arm, at 12 weeks.

Lilly has pointed to secondary endpoints as further evidence for orforglipron's potential as "a convenient alternative to injectable treatments […] that could support early intervention and long-term disease management."

That includes data showing that nearly 60% of patients taking the drug at the 36mg dose achieved 10% weight loss, versus 8.6% of the placebo group, as well as improvements in cardiovascular risk biomarkers like non-HDL cholesterol, triglycerides, systolic blood pressure, and C-reactive protein.

The company added that it is "making substantial investments to meet anticipated demand at launch" for the drug, which remains well ahead of most potential rivals in the oral category. Novo Nordisk is still preparing a phase 3 programme for oral amycretin, while candidates from other companies are even further back in development.

Strong showing for injectable

Lilly revealed the ATTAIN-1 data at the same time as it reported strong sales growth for its injectable obesity therapy Zepbound (tirzepatide) in the second quarter of the year, with sales up 172% to $3.38 billion, ahead of analyst expectations. Mounjaro, the formulation of tirzepatide used for diabetes, also did better than expected with growth of 68% to $5.2 billion.

The strong performance, which has prompted Lilly to raise its sales guidance for the full year by $1.5 billion to $60-$62 billion, comes after Novo Nordisk said it was trimming forecasts due to competitive pressures, including compounded versions of its GLP-1 drug semaglutide.