Dive Brief:

• Eli Lilly’s weight loss pill orforglipron succeeded in a Phase 3 clinical trial in diabetes, helping study participants control their blood sugar while hinting at weight loss that might be comparable to injectable obesity medicines.  
• Enrollees in the 40-week trial saw their blood sugar levels reduced by up to 1.6 percentage points, with 65% achieving healthy levels, the company said Thursday. Notably, the drug spurred an average of up to 8% weight loss, or about 16 pounds, at the highest dose, indicating that the effects will be even greater in Lilly’s longer Phase 3 trial in obesity. Lilly said trial participants “had not yet reached a weight plateau” when the diabetes study ended.
• A pill with similar weight loss effects to injectable GLP-1 therapies — like Novo Nordisk’s Wegovy or Lilly’s own Zepbound — could change the dynamics of the lucrative market for obesity drugs. As a small molecule, or chemical, drug, orforglipron would also be easier to manufacture than its injectable counterparts, which have faced production constraints that have limited uptake. 

Dive Insight:

Orforglipron is one of the most closely watched drugs in the pharmaceutical industry. If successful in additional late-stage trials, it could offer people with diabetes or obesity a convenient, oral alternative to injectable therapies and quickly be scaled into mass production. 

The drug could also give Lilly a bigger share of a market estimated to top $100 billion annually by next decade. Lilly’s already made significant inroads on that front, with Zepbound outperforming Wegovy in a head-to-head trial. It could further press its top rival with orforglipron, which is expected to produce Phase 3 results in obesity later this year and could be submitted to regulators afterwards. Novo, by comparison, hasn’t sought approval in obesity for an oral peptide drug called Rybelsus that’s shown it can stimulate weight loss. 

One of Lilly’s top competitors, Pfizer, also suffered a significant setback earlier this week, when it abandoned development of a rival pill called danuglipron. 

The diabetes trial toplined Thursday, Achieve-1, enrolled 559 people with Type 2 diabetes and randomized them to receive one of three daily doses of orforglipron or a placebo. The people in the drug arms started with just a 1 milligram dose of orforglipron and gradually increased to their assigned dose of 3, 12 or 36 milligrams.

Blood sugar reductions, from 8% on average at the study’s start, were 1.3, 1.6 and 1.5 percentage points respectively in the 3, 12 and 36 mg groups, compared to a 0.1 percentage point reduction in the placebo group. Trial participants, who had a baseline mean body weight of 199 pounds, lost 4.7%, 6.1% and 7.9% of their weight on the three doses, versus 1.6% in those receiving a placebo.

Orforglipron was associated with the same gastrointestinal side effects commonly seen with GLP-1 therapies. Notably, though, the rates of such side effects appear to be lower than what Lilly observed in earlier testing, which could be attributed to the gradual dosing increase in the Phase 3 study, wrote Evercore ISI analyst Umer Raffat.

Elevated liver enzymes, a sign of possible organ damage, had also been seen in earlier testing. Though Lilly didn’t provide specific details, it did say Thursday that “no hepatic safety signal was observed.”

In a separate research note, Leerink Partners analyst David Risinger called the results “picture perfect.” Though the data are from a shorter trial in diabetes, the drug’s safety and efficacy appear comparable to Novo’s drug, Risinger wrote. Multiple analysts had a similarly positive take, arguing orforglipron could set the standard for oral obesity drugs.

The results have implications for others following with such medicines. Structure Therapeutics is developing a small molecule GLP-1 pill, while Viking Therapeutics and Zealand Pharma have peptide counterparts that could be at a disadvantage. And Novo, without a “viable” oral drug, may start facing tougher competition next year should orforglipron get to market for obesity and diabetes, Jefferies analyst Benjamin Jackson wrote.

Lilly shares rose nearly 15% in morning trading, swelling its market value by more than $100 billion.