Terns’ oral GLP-1 shows promising weight loss in Phase 1 trial

Terns Pharmaceuticals has revealed promising early-phase results for its oral GLP-1 agonist, indicating it could offer more tolerability at higher doses compared to existing oral GLP-1 therapies. During the multiple ascending dose segment of Terns' Phase 1 trial, 67% of participants who received the highest daily dose of 740 mg of TERN-601 lost at least 5% of their body weight within 28 days. This high dose also produced a placebo-adjusted average weight reduction of 4.9%, with a statistical significance of p<0.0001. The weight loss outcomes were presented according to dose groups without pooling the data.

The trial included overweight and obese adults with a Body Mass Index (BMI) between 27 kg/m² and 40 kg/m². To give context, Novo Nordisk's semaglutide showed around a 2% weight reduction at four weeks in its STEP 1 trial, with weight loss reaching 16% by 68 weeks. Similarly, Eli Lilly’s tirzepatide achieved an average 2% weight loss at four weeks in the SURPASS-2 study, with a total weight loss of 13% at 40 weeks. However, both of these drugs are administered via injection.

Following the announcement, Terns Pharmaceuticals saw a roughly 7% increase in its share price in premarket trading on Monday. Regarding safety, TERN-601 was generally well accepted across all dosage levels, with no interruptions, reductions, or discontinuations needed. There were no severe or serious adverse reactions, according to the company's release. Terns plans to present these findings at an upcoming scientific conference.

Chief Medical Officer Emil Kuriakose noted that Terns has identified a range of clinically effective and well-tolerated doses to move forward into Phase 2, which is scheduled for the coming year. The California-based biotech firm highlighted several distinctive properties of its drug that could differentiate it from other GLP-1 agonists. These properties include low solubility and high permeability in the gut, allowing for sustained action on the target and a more consistent pharmacokinetic profile. Additionally, the drug's minimal free circulation within the body may enhance tolerability at higher doses when combined with its pharmacokinetic benefits.

With these results, Terns Pharmaceuticals joins numerous other companies in the race to develop a new generation of weight loss medications with unique characteristics. Lilly’s retatrutide, which targets GLP-1, GIP, and glucagon, seems to produce more significant weight loss than some drugs currently on the market based on Phase 2 data. Meanwhile, Amgen is promoting MariTide for its potential to better maintain weight loss by activating the GLP-1 receptor and blocking the GIP receptor. In June, Altimmune provided a comprehensive Phase 2 analysis of pemvidutide, its GLP-1/glucagon dual receptor agonist, which purports to be more effective in preserving lean muscle mass.