Pill structure leads to weight loss in obesity study

An experimental oral GLP-1 drug has demonstrated promising results in aiding weight loss for individuals with obesity, according to initial findings disclosed by Structure Therapeutics. The study, which is in its Phase 2a stage, enrolled 64 overweight and obese participants. Over a period of three months, those who took the experimental drug, named GSBR-1290, saw an average weight reduction of 6.2% more than those who were given a placebo. Impressively, one-third of the participants on GSBR-1290 lost a minimum of 10% of their body weight, a milestone that none of the placebo group achieved.

Following the announcement, Structure Therapeutics saw a significant surge in its share price, climbing more than 50%. This resurgence in market confidence comes after previous setbacks in the company’s stock performance, attributed to disappointing data from another trial. The company is now planning to advance to a Phase 2b study, which will explore different dosages of GSBR-1290.

The context for Structure's research is the competitive landscape of GLP-1 drugs, which are used for both diabetes management and weight loss. Major pharmaceutical companies like Novo Nordisk and Eli Lilly have already made significant strides with injectable GLP-1 treatments such as Wegovy and Zepbound. However, Structure Therapeutics aims to differentiate itself by developing an effective oral alternative, which could offer greater convenience and potentially lower costs.

In December, Structure Therapeutics released data from a separate study involving Type 2 diabetes patients treated with GSBR-1290. While the drug showed efficacy in reducing blood sugar levels, the weight loss results were less impressive, leading to a drop in the company’s stock value. The latest data, however, have helped restore some investor confidence.

In addition to the Phase 2a results, Structure Therapeutics has announced findings from a pharmacokinetic study involving a tablet form of GSBR-1290, as opposed to a capsule. Among the 54 participants in this trial, weight loss averaged between 6.2% and 6.9% compared to the placebo, with variations depending on the dosage.

Analysts from Leerink Partners and Cantor Fitzgerald have noted that the results from Structure Therapeutics' studies are competitive with those of Eli Lilly's oral GLP-1 candidate, orforglipron. Common side effects of GSBR-1290 included nausea and vomiting, although these symptoms were primarily observed early in the treatment and tended to decrease as the dosage was adjusted. A small percentage of participants—5% in the Phase 2a study and 11% in the pharmacokinetic study—discontinued the treatment due to adverse effects. Importantly, there were no reported cases of liver injury or sustained increases in liver enzymes.

David Risinger, an analyst at Leerink Partners, commented that a monthly titration schedule for GSBR-1290 could significantly improve its tolerability. The advantages of small molecule pills like GSBR-1290 and orforglipron include ease of administration and potentially lower production costs, making them a promising alternative to existing injectable treatments.

Structure Therapeutics has plans to initiate a 36-week Phase 2b study focusing on obesity in the final quarter of the year. CEO Raymond Stevens highlighted in a statement that the company is optimistic about exploring higher doses of GSBR-1290 in forthcoming studies.