An experimental GLP-1 obesity drug from Terns Pharmaceuticals led to a 5.5% reduction in body weight in a small study, continuing to build its case as a potential oral alternative to currently available injectable obesity medicines. With these encouraging early data in hand, Terns now aims to see if the drug can replicate the results in a larger mid-stage clinical trial expected to begin next year.
The data announced Monday are from a multiple-ascending dose Phase 1 clinical trial that enrolled 37 healthy volunteers who were obese or overweight. These participants were randomly assigned to receive one of three doses of the study drug, code-named TERN-601, or a placebo.
TERN-601 is an oral, small-molecule designed to activate the GLP-1 receptor. The main goal of the drug’s Phase 1 study is assessing the once daily pill’s safety and tolerability over the course of 28 days of treatment. Adverse effects reported were mainly gastrointestinal, which is no surprise as these complications are a known complication of the GLP-1 drug class. Such side effects for TERN-601 were classified as mostly mild, but it’s the weight-loss results that keep Foster City, California-based Terns competitive with other companies developing oral obesity medications.
The Phase 1 data for TERN-601 show dose-dependent weight loss. For the low-dose cohort, 11% of participants achieved weight loss of 5% or greater after 28 days. For the middle dose, results showed 33% of participants achieved this mark. The best result was in the high dose group, where 67% of participants in the arm achieved an average weight loss of 5.5%. The average weight reduction in the placebo arm was 0.6%.
Cross-trial comparisons are always fraught with risk, due to differences such as trial design and duration of treatment. But the Terns results meet the 5% weight-loss benchmark measured at one month that other companies achieved with their oral drugs. Nearly a year ago, Structure Therapeutics reported preliminary Phase 1 data showing the highest dose of its once-daily pill, GSBR-1290, led to an average 5.4% loss in body weight for the high-dose group measured at four weeks. In June, Structure reported preliminary Phase 2a data showing this pill achieved a statistically significant 6.2% placebo-adjusted average weight loss measured at 12 weeks.
In March, Novo Nordisk reported its oral drug, amycretin, achieved 13.1% weight loss, but that was measured over a span of 12 weeks and this analysis covered just 16 participants. Viking Therapeutics followed with results showing an average of 5.3% weight loss from baseline for VK2735, an oral drug designed to activate both the GLP-1 and GIP receptors. In July, Roche reported preliminary Phase 1 data showing that four weeks of treatment with its oral GLP-1 drug, CT-996, led to an average 7.3% loss of body weight.
While Eli Lilly is a leader in obesity medications with its injectable GLP-1 and GIP receptor agonist, Zepbound, the pharmaceutical giant is also in late-stage clinical testing with an oral GLP-1 drug called orforglipron. Published Phase 2 results showed this once-daily pill weight reductions across four doses of the study drug that ranged from 9.4% to 14.7% measured at 36 weeks. This Lilly study randomized a total of 272 participants.
In an investor presentation, Terns said it plans to solicit feedback from scientific advisors based on the Phase 1 data. The company will also seek feedback from regulators about the design of a mid-stage clinical trial.
“These data validate the potential of TERN-601 for the treatment of obesity as monotherapy or in combination with agents such as TERN-501, our internally discovered, clinical stage THR-beta agonist, or a GIPR modulator from our TERN-800 series,” Terns CEO Amy Burroughs said in a prepared statement. “With operational preparations well underway, we look forward to swiftly advancing this promising product candidate into Phase 2 clinical development in 2025.”
Photo: Peter Dazeley, Getty Images
