Lilly Trims Phase 2 Trials for Oral GLP-1 Candidate Naperiglipron, Focuses on Obesity Study

Eli Lilly has made a strategic decision to terminate two of its three ongoing phase 2 trials for naperiglipron, an oral GLP-1 receptor agonist candidate. This move comes as the pharmaceutical giant intensifies its efforts in the competitive oral GLP-1 market, with a particular focus on obesity treatment.

Trial Terminations and Ongoing Research

The company has ended two mid-stage studies that were initiated over the summer. One trial targeted patients with overweight or obesity and type 2 diabetes, while the other aimed to evaluate the drug's effects in adults with a healthy body mass index. Both studies were originally scheduled to run for approximately one year.

Despite these terminations, Lilly continues to pursue research on naperiglipron through a third phase 2 trial. This ongoing study, highlighted in the company's recent second-quarter earnings presentation, aims to enroll 275 patients with obesity or overweight. With a projected completion date of September 2026, this trial is expected to inform the future direction of the naperiglipron program.

Orforglipron: Lilly's Lead Oral GLP-1 Candidate

While adjusting its strategy for naperiglipron, Lilly has been making significant progress with orforglipron, its lead oral GLP-1 drug. Recent late-stage data for orforglipron has shown promising results:

• In a obesity trial, the highest dose of orforglipron led to an average weight reduction of 12.4% (27.3 pounds).
• A separate phase 3 study in patients with Type 2 diabetes demonstrated an average weight reduction of 10.5% over 72 weeks, along with improvements in blood sugar levels and cardiometabolic risk factors.

These results, while clinically significant, fell short of the 15.7% weight loss reported for Novo Nordisk's CagriSema. This comparison led to a 13% drop in Lilly's share price following the data release, highlighting the high expectations in the GLP-1 obesity market.

Market Dynamics and Future Outlook

The oral GLP-1 market is becoming increasingly competitive, with pharmaceutical companies vying for dominance in obesity and diabetes treatment. Lilly's Chief Scientific Officer, Daniel Skovronsky, M.D., Ph.D., has defended orforglipron's performance, stating it is "as good as it gets for GLP-1 monotherapy here in the once-a-day small molecule [space]."

As Lilly refines its clinical strategy, the company's focus on the ongoing naperiglipron obesity trial and the advancement of orforglipron underscore its commitment to developing effective oral treatments for obesity and related metabolic disorders. The results of these studies will likely play a crucial role in shaping Lilly's position in the evolving GLP-1 market landscape.