Lilly trial shows weight loss with experimental pill flattens over time

By Deena Beasley

Sept 16 (Reuters) - Eli Lilly's LLY.N experimental GLP-1 pill helped people lose about 12% of their body weight, with weight loss plateauing for most patients in the 72-week trial, according to full study results presented at a medical meeting on Tuesday.

Lilly had announced in August that the Phase 3 study of the daily pill, orforglipron, met its main goals, but the weight loss was less robust than previous trial results for Novo Nordisk's NOVOb.CO weekly injectable GLP-1 drug Wegovy.

That news sent Lilly's shares down 14%. Year-to-date, the company's shares have fallen about 1%.

Results from a late-stage study of the drug orforglipron were presented at a European medical meeting and published in the New England Journal of Medicine. The trial enrolled over 3,000 non-diabetic participants who were obese or overweight with a weight-related health problem.

Lilly said orforglipron showed clinically meaningful improvements across key cardiovascular risk factors, including cholesterol levels and blood pressure. It said the highest dose of the drug reduced a key marker of inflammation by 47.7%.

The most commonly reported side effects were mild-to-moderate and gastrointestinal. The rate of nausea for high-dose patients was 33.7%, compared with 10.4% for placebo patients.

In the high-dose orforglipron group, 10.3% of patients dropped out of the trial due to side effects, compared with 2.6% of placebo patients.

Lilly said liver safety was thoroughly evaluated and concluded that there was no concerning pattern of liver issues among patients taking the drug. High liver enzyme levels were reported in seven orforglipron patients, but alternative causes were identified, researchers said.

During the 72-week trial, three deaths were reported: one low-dose orforglipron patient, one mid-dose patient and one placebo patient.

Five cases of mild pancreatitis occurred in orforglipron patients. No cases of medullary thyroid cancer were reported.

An increase in the mean pulse rate of 4.3 to 5.3 beats per minute occurred in the orforglipron groups, compared with an increase of 0.8 beat per minute in the placebo group, which researchers said was consistent with findings observed with injected GLP-1 drugs.

In a previous 36-week Phase 2 trial, orforglipron was shown to reduce body weight by nearly 15% without an apparent plateau. Researchers said that despite the recent study's 72-week duration, weight reduction was not greater, which could be due to differences in trial design, including more geographic diversity and a higher percentage of men.