Lilly’s GLP-1 pill cuts body weight by 12.4% in trial, lagging Novo’s Wegovy

Eli Lilly said on Thursday that its experimental GLP-1 pill helped patients lose 12.4% of their body weight after 72 weeks in a late-stage study, less than previous trial results for Novo Nordisk's injectable obesity treatment Wegovy.

Lilly shares tumbled about 14% in premarket trading as the data failed to meet the high bar set by investors.

Unlike injectable obesity drugs, which are peptides designed to mimic the appetite-controlling GLP-1 hormone, orforglipron is a small molecule pill that is easier to manufacture and package, said Kenneth Custer, president of Lilly's cardiometabolic health division.

Lilly, whose injectable GLP-1 Zepbound competes directly with Wegovy, views the once-daily pill as a promising alternative to injections that could be used for early intervention and long-term disease management, Custer said.

Patient preference also leans towards oral medications over injections. Several studies have shown that a significant portion of patients prefer pills due to convenience and a dislike of needles.

"We have pretty big aspirations for how many patients orforglipron could help," he said, adding that Lilly still expects to file for regulatory approvals of the once-daily pill before the end of the year.

In the over 3,000-person study of overweight or obese adults with weight-related health issues, but not diabetes, those who received the highest 36-milligram dose of orforglipron on average shed 12.4% of their weight versus 0.9% for those who received a placebo.

Patients on the 6 mg dose of the Lilly drug lost 7.8% of their weight.

After early trial results, expectations were high for the drug to do better than Novo's Wegovy, said Barclays analyst Emily Field. "[But] it's worse than Wegovy so it's a shock."

The most common side effects seen in the study were mild-to-moderate gastrointestinal issues. The rate of nausea for high-dose patients was 33.7%, while 24% experienced vomiting, compared with 10.4% and 3.5%, respectively, for the placebo group.

At least two analysts said that the tolerability profile of orforglipron also came in below what was seen in the drug's trial with diabetes patients.

"While we still see this as a manageable profile, rates of nausea and vomiting may be higher than investor expectations," BMO Capital Markets analyst Evan Seigerman said.

Just over 10% of the high-dose patients dropped out of the trial due to adverse side effects. No liver safety issues were seen, Lilly said.

At least three analysts said the market had been looking for orforglipron to match Wegovy's 14.9% weight loss over 68 weeks, as shown in a 2021 trial, with some expecting the pill to surpass Novo's popular drug.

"That is a best case scenario for Novo ... The competitive threat from Lilly is suddenly much weaker than anticipated," Novo and Lilly shareholder Markus Manns told Reuters

Zepbound and Wegovy currently dominate the weight-loss market, which some analysts expect to reach $150 billion by the early 2030s.

The US Food and Drug Administration is reviewing a high-dose oral version of Wegovy for potential approval later this year. Novo said it helped overweight or obese adults lose 15% of their body weight in a late-stage trial.

Custer said orforglipron can be taken without restrictions on food and water.

Lilly said orforglipron also lowered markers of heart disease risk, including cholesterol, triglycerides, and blood pressure, across all doses.

Wegovy has been approved to reduce the risk of major heart problems, and Lilly last week released data showing the heart-protective qualities of diabetes treatment Mounjaro, which has the same main ingredient as Zepbound. Heart disease approvals would greatly enhance the likelihood of insurance coverage for weight-loss drugs.

The company announced earlier this year that a Phase 3 study found that type 2 diabetes patients lost nearly 8% of their body weight after 40 weeks on orforglipron.

Lilly has also said it has begun manufacturing the drug in order to stockpile supply ahead of a commercial launch, which should help avoid shortages experienced when early demand for the injectables far outstripped supply.

The full results from the Lilly-backed trial will be presented next month at a major European diabetes meeting, the Indianapolis-based drugmaker said. — Reuters