Garetosmab

VIENNA — Eli Lilly was undoubtedly the star of this year’s congress of the European Association for the Study of Diabetes. Despite being slightly less effective than Novo Nordisk’s rival pill, Lilly’s oral obesity therapy orforglipron could do well in the market. And its diabetes shot Mounjaro looks likely to become the first of the new-generation incretins to crack the pediatric space. But many other companies also had a presence at the meeting in Vienna, some with GLP-1 therapies and some with more adventurous mechanisms. An update from the Phase 2 trial of Regeneron’s muscle-building drug trevogrumab was presented on Wednesday. The trial is assessing the ability of the anti-GDF8/anti-myostatin antibody to preserve lean mass in patients who are also taking Novo Nordisk’s obesity shot Wegovy. The new data showed that, of the weight lost by obesity patients after 26 weeks of therapy with Wegovy plus a low or high dose of trevogrumab, around 17% and 18% was lean mass, respectively. Of the weight lost by patients given Wegovy monotherapy, about 33% was lean mass. Updated data from the trial’s triplet arm, in which patients took Regeneron’s investigational anti-activin A antibody garetosmab as well as Wegovy and high-dose trevogrumab, were also presented. Here, just 7.4% of the weight lost was lean mass. These figures are not hugely different from the interim cut released in June . However, Regeneron reiterated that there were two deaths, both in the triplet group, that had been disclosed in June. In one case, the cause is unknown, although Regeneron said the patient had “multiple cardiovascular risk factors.” The second death was due to a cardiac arrest in a patient with a history of cardiovascular disease. Regeneron said it had “not identified a causal association” between the drug regimen and the deaths. The triplet regimen saw a “substantially higher” rate of discontinuations because of tolerability issues than the other two arms. Regeneron said that further studies are warranted, though it is unclear if this refers to the doublet or triplet regimen. Regeneron is separately seeking approval of garetosmab for the rare bone disease fibrodysplasia ossificans progressiva. Mid-stage trial data on a quadruple agonist developed by the California biotech Biomed Industries was also presented on Wednesday. Bioglutide, also called NA-931, is an oral small molecule that hits the receptors for GLP-1, GIP, glucagon and insulin-like growth factor-1 (IGF-1). In the 125-patient Phase 2 study, obesity patients taking one pill a day for 13 weeks had a maximum body weight reduction of 14.8% at the 150 mg daily dose, which calculates to 13.2 percentage points greater than placebo. Gastrointestinal adverse events were mostly mild, with nausea and vomiting reported as “insignificant.” Diarrhea occurred in 8.1% of bioglutide-treated subjects, compared to 3.2% in the placebo group. According to the EASD abstract, no muscle loss was observed. The company intends to take bioglutide into a Phase 3 program. Wednesday also saw presentation of results from a small Phase 1b/2a study of a GLP-1 developed by the Indian company Sun Pharmaceutical, in patients with obesity and metabolic dysfunction-associated fatty liver disease (MAFLD). In a subset of patients with BMI of less than 40 kg/m2 and blood sugar levels of at least 6.0%, their body weight fell by an average of 6.8% after 13 weeks of treatment with utreglutide. In the placebo group, weight fell by 3.1% but this group was not required to meet the same blood sugar criterion as those who received the drug. These patient groups were small, with just eight patients getting utreglutide and six receiving placebo. Utreglutide, with the codename GL0034, is also in a Phase 2 study in MASH with data due late next year or early in 2027. Another Asia-based biotech, Beijing QL Biopharmaceutical, presented data on a GLP-1 at the conference on Wednesday — this time, a long-acting shot with potential for monthly administration. Zovaglutide, also known as ZT002, was tested in around 300 nondiabetic obesity patients. Two doses, 80 mg or 160 mg, were given every two weeks and every four weeks in different groups. After six months, those given 80 mg monthly lost 10.6% of their weight, while those on the 160 mg monthly dose lost 13.8%. The same doses given every two weeks resulted in weight loss of 12.5% and 14.4%, respectively. All zovaglutide groups demonstrated statistically significant greater weight loss versus placebo, and no plateau was reached. Gastrointestinal adverse events (AEs) were similar to those of marketed GLP-1s, QL said , though one patient quit the trial due to gastrointestinal AEs. The company said that the data support a Phase 3 trial of monthly zovaglutide in obesity patients. Novo Nordisk reported a new data point from its early-stage trial of the GLP-1 and amylin combo shot known as amycretin on Tuesday. A cohort in the drug’s Phase 1b/2a obesity trial , whose dose was escalated up to 60 mg, lost 24.3% of their body weight at eight months, whereas placebo patients lost 1.1%. This was significantly higher, at a p-value of less than 0.001. The researchers said amycretin was “considered safe and tolerated” up to 60 mg. The most common TEAEs were nausea, vomiting and diarrhea, and most were mild to moderate. Editor’s note: This story was updated to note that the deaths in Regeneron’s study had already been disclosed, and that the company is seeking approval of garetosmab in a rare bone condition.

Regeneron plans to start a phase 3 trial in adolescents and children with FOP next year.\n Regeneron is racing to regulators after reporting a phase 3 win in an ultrarare disease. The biotech plans to file for FDA approval of garetosmab in fibrodysplasia ossificans progressiva (FOP) by the end of 2025 on the strength of a pivotal trial that read out on Wednesday.The study randomized 63 adults with FOP to receive one of two doses of the anti-activin A antibody garetosmab or placebo every four weeks for 56 weeks. At the end of the trial, there were one and two new abnormal bone lesions, respectively, in patients on the low and high doses of garetosmab. Regeneron reported 19 new lesions in the placebo group. With a 90% or greater reduction in lesions in both treatment arms, the study met its primary endpoint. The outcome supports Regeneron’s findings that the activin A protein is critical to the development of heterotopic ossification lesions, deposits of bone in soft tissues that define FOP.Regeneron named clinician-assessed flare-ups, a term for cases of episodic, localized inflammation, as a key secondary endpoint. There were 70 flare-ups in the placebo arm, compared to 53 cases on the low dose of garetosmab. That 20% reduction wasn’t statistically significant. But the high dose performed better, with nine flare-ups and a statistically significant 89% reduction compared to placebo. Nobody on garetosmab stopped treatment and there was no dose-dependent increase in nosebleeds, a side effect seen in a phase 2 trial of the antibody. There were no serious bleeding events and no deaths.Safety was a key area of focus. When Regeneron reported phase 2 data in 2020, the company planned to seek FDA approval early the following year. However, the company paused the study later in 2020 after multiple patients died in the extension part of the trial. Five out of 44 patients died. Researchers said the events were unlikely to be related, noting that there was no clear pattern to link the deaths to the treatment or to the mechanism of action, but were unable to rule out a causal connection to garetosmab. Regeneron dropped garetosmab from its list of planned FDA filings for the year partway through 2021. Based on the phase 3 results, the Independent Data Monitoring Committee recommended switching patients on placebo to garetosmab as soon as possible. Regeneron is moving quickly, too, with a filing for FDA approval planned for this year and global submissions on the schedule for 2026. The company plans to start a phase 3 trial in adolescents and children with FOP next year. Ipsen won FDA approval for Sohonos in adults and children with FOP in 2023. However, after a troubled development, the drug has underperformed commercially. Ipsen took (PDF) an impairment loss of 279 million euros ($330 million) related to the product. Sohonos sales fell (PDF) 20% to 8.3 million euros in the first half of 2025.The French drugmaker is developing a next-generation FOP drug, fidrisertib. Data from a registrational phase 2 trial of the candidate are expected this year. Ipsen has enrolled children as young as five years in the study and expects fidrisertib to be free from some of the safety problems that have impeded sales of Sohonos.