Garetosmab

Regeneron reported efficacious early results on its T cell engager Lynozyfic in smoldering multiple myeloma, a precancerous condition that can turn into active multiple myeloma. The study is part of a bid to expand the use of its recently approved bispecific antibody. In the Phase 2 study, all 19 people responded to Lynozyfic, which is also known as linvoseltamab. About three-quarters of patients achieved a “very good partial response,” meaning that levels of an abnormal protein that’s a signal of the disease fell by at least 90% but were still detectable. Regeneron said all responses were ongoing as of May 28. “Our conversation is shifting from treating to potentially — in premalignant conditions — asking the question now, can we cure people? Are we there yet? No,” said Andres Sirulnik, Regeneron’s head of hematology clinical development. “We are asking that question, and that means going to early lines of therapies with a shorter duration or a fixed duration of treatment, and see whether we can obtain long-term remissions,” he said. Regeneron is planning to pit the drug against Johnson & Johnson’s Darzalex in a Phase 3 trial of smoldering multiple myeloma that’s slated to begin late this year or early next year, Sirulnik said. J&J is awaiting an FDA decision on Darzalex Faspro, an injectable version of the drug, in this condition following a favorable advisory committee vote in May. The Tarrytown, NY biotech noted that the safety of Lynozyfic “appeared more favorable” compared to people with more severe disease of relapsed or refractory multiple myeloma. Regeneron reported no ICANS, a form of neurotoxicity, and no treatment discontinuations. It reported that 10 of 24 patients experienced cytokine release syndrome, a side effect of immunotherapies where the immune system overactivates. All of those cases were mild to moderate. Nineteen of 24 patients faced infections, three of which were grade 3. Lynozyfic is a BCMAxCD3 T cell engager, latching onto a protein called BCMA on myeloma cells as well as CD3 on T cells. By bridging the two together, the drug’s goal is to trigger T cells to attack the cancer cells. In July, the FDA granted accelerated approval to Lynozyfic for adults with multiple myeloma who have tried at least four previous treatment regimens. The approval followed an initial rejection last year over manufacturing problems. The new Lynozyfic data cap off an active week of trial readouts for Regeneron — starting with Phase 3 results of an ultra-rare bone disease drug garetosmab , for which the biotech is planning to ask the FDA for approval. Regeneron also shared detailed data on its muscle-sparing regimens for weight loss.

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.