Terns Pharmaceuticals abandons its oral GLP-1 after weak Phase 2 data and liver signals

Terns Pharmaceuticals said on October 21 that it is ending development of TERN-601, an experimental once-daily oral GLP-1 receptor agonist for obesity, after disappointing Phase 2 results ^[2]. The company also said it will not invest further in metabolic disease and will shift its focus to a cancer drug, TERN-701, aimed at chronic myeloid leukemia ^[2].

In the 12-week trial, TERN-601 produced a maximum placebo-adjusted weight loss of 4.6% ^[2]. That is well below the weight loss seen with approved injectable GLP-1 drugs and with Eli Lilly's oral orforglipron (Foundayo), which has posted stronger late-stage results. Terns Chief Executive Officer Amy Burroughs said the bar for a competitive oral GLP-1 drug is high, requiring safety, tolerability, and efficacy together, and that TERN-601's data "did not meet this threshold and likely preclude further development" ^[2].

Safety findings added to the setback. About 11.9% of the 134 people in the study stopped taking the drug because of side effects, mostly gastrointestinal problems like nausea and vomiting ^[2]. Most of these were described as mild or moderate ^[2]. More seriously, three participants had grade 3 liver enzyme elevations after they stopped treatment, and two of those cases were linked to the drug itself, including one confirmed by a liver biopsy ^[2]. Terns said the liver signal was unexpected because earlier studies had not shown similar problems ^[2].

Analysts drew a comparison to Pfizer's earlier oral GLP-1 candidates, danuglipron and lotiglipron, both of which were discontinued over liver safety concerns ^[2]. William Blair analyst Andy Hsieh said he was "not surprised by the liver toxicity signal," noting that TERN-601 shares a similar chemical structure, or pharmacophore, with those two discontinued Pfizer drugs ^[2]. Shares of Terns fell more than 16% in extended trading after the announcement ^[2].

Why it matters for patients

This news does not affect anyone currently taking an approved GLP-1 medicine such as Ozempic, Wegovy, Rybelsus, Mounjaro, or Zepbound. TERN-601 was never approved and was only in a mid-stage trial ^[2]. Its failure is a reminder that not every drug in this fast-growing class works as hoped, and that oral versions in particular carry their own safety questions that differ from the injectable drugs already on the market.

The liver enzyme elevations seen in a small number of trial participants are a specific safety signal tied to this one experimental drug and its chemical structure, not to GLP-1 medicines generally ^[2]. Still, the pattern echoes earlier problems with other oral candidates from Pfizer, suggesting that some chemical approaches to oral GLP-1 drugs may carry liver risks that trial sponsors need to watch closely ^[2].

For people weighing their options, the episode underscores that the field of oral GLP-1 pills is still young and unsettled. Some programs, like Eli Lilly's orforglipron, have moved forward with stronger results, while others, like Pfizer's earlier candidates and now Terns's TERN-601, have been stopped over safety or efficacy concerns ^[2]. This is a reminder that the source material available does not describe every drug in development the same way, and results vary widely by molecule.

What happens next

Terns Pharmaceuticals said it will no longer invest in metabolic disease research and will direct its resources toward TERN-701, a treatment for chronic myeloid leukemia ^[2]. No further details on additional trials or a timeline for winding down the TERN-601 program were included in the available reporting.