Inversago Pharma, Inc.

A drug that Novo Nordisk acquired to expand its prospects in metabolic disorders has failed a mid-stage clinical trial in diabetic kidney disease. The results also showed signs of a neuropsychiatric side effect that could crimp plans to develop this pill in other metabolic indications, including obesity. The Phase 2b results for the drug, monlunabant, were tucked into Novo Nordisk’s report of full-year 2024 financial results released Wednesday. The company said the once-daily pill did not meet the main goal of showing statistically significant improvement on the measure of certain compounds in urine that are indicative of kidney disease. The most common adverse events were gastrointestinal, and the company said the vast majority of them were mild to moderate. But Novo Nordisk also noted mild-to-moderate neuropsychiatric side effects that were more frequent in patients who received the study drug. Neuro effects are a risk for monlunabant and others in its drug class, which targets cannabinoid receptor type 1 (CB1). This receptor, found mainly in the central nervous system but also in some peripheral organs and tissues, regulates various physiological processes, including appetite. Targeting it for obesity was validated by rimonabant (brand name Acomplia), a Sanofi drug approved in Europe in 2006. But hitting CB1 receptors in the brain led to psychiatric effects. Those complications led Sanofi to withdraw the product from the market in 2008. presented by Health IT Transforming Patient Care: The Role of AI-Powered Assistants The progress in artificial intelligence (AI) is reshaping patient care, across various dimensions, from facilitating faster discharge to curating treatment plans and suggesting lifestyle changes. By IT Medical Monlunabant, formerly INV-202, came from Novo Nordisk’s 2023 acquisition of Inversago Pharma. The Canadian company designed this small molecule to preferentially target CB1 receptors in the gastrointestinal tract, liver, kidneys, and pancreas. The M&A deal followed Inversago’s report of Phase 1 data showing clinically significant weight loss. Last September, Novo Nordisk reported Phase 2 obesity study results showing statistically significant weight loss at 16 weeks across all three doses tested. While gastrointestinal side effects were mild to moderate, the results also showed mild-to-moderate neuropsychiatric effects such as anxiety, irritability, and sleep disturbances. Novo Nordisk said these effects were more frequent in those who treated with the study drug compared to those who received a placebo. At the time of the trial readout, Martin Lange, executive vice president and head of development at Novo Nordisk, said the results indicate the drug’s weight-lowering potential, adding that more work is needed to determine the optimal dose to balance safety and efficacy. But the signs of neuropsychiatric effects for monlunabant, despite a design intended to avoid such problems, leaves other companies with an opportunity to show differentiation with their peripherally restricted CB1-targeting drugs. Skye Bioscience aims to drug CB1 with nimacimab. As a large molecule that does not easily penetrate the blood brain barrier, this antibody should avoid sparking the neuropsychiatric side effects observed with small molecules that target CB1, Skye Chief Development Officer Tu Diep told MedCity news last year. A Phase 2 test of the Skye drug in obesity is expected to yield data later this year. Exclusive Improving the Healthcare Financial Experience to Help Care Flow Zelis CEO Amanda Eisel shares her perspective on how the company is solving the problems of a fragmented health financial system to benefit all. By Stephanie Baum Meanwhile, Corbus Pharmaceuticals is developing what it describes as a next-generation peripherally restricted CB1 receptor agonist. In preclinical research presented at the Obesity Week 2024 conference in November, Corbus reported that brain levels of its drug, CRB-913, were 15-fold lower compared to monlunabant that was administered to mice at the same dose. Corbus expects to begin a Phase 1 test of its drug in the first quarter of 2025. In Novo Nordisk’s report of third quarter 2024 financial results, the company said it expected to begin a larger Phase 2b obesity test for monlunabant in 2025. The goal of this study is to further investigate the dosing and safety profile of the drug over a longer period of time in a global population. Regarding monlunabant’s mid-stage failure in kidney disease, Novo Nordisk said Wednesday that it is evaluating this drug for further clinical development in this indication. Image: DrAfter123, Getty Images

Novo Nordisk’s $1 billion bet last year on a small Canadian biotech could expand the Danish drug giant’s arsenal of obesity medicines, but it will first have to address safety concerns. On Friday, Novo said its experimental drug monlunabant helped people lose weight at statistically significant levels in a Phase 2a trial . The oral small molecule is a CB1 inverse agonist, and Novo acquired it through a takeover of the biotech Inversago Pharma, announced in August 2023. In the Phase 2a trial, Novo said all once-daily doses of monlunabant hit statistical significance at reducing weight from baseline compared to placebo. But the higher doses didn’t have as much of an impact as expected. After 16 weeks on the lowest dose of 10 mg, trial participants on its drug experienced a weight loss of 7.1 kg versus 0.7 kg for those taking the placebo. At the higher doses of 20 mg and 50 mg, Novo said there was “limited additional weight loss.” The data didn’t excite the market. Novo’s US shares $NVO were down about 4.3% Friday morning, while shares of Corbus Pharmaceuticals $CRBP tanked 63% as investors took Novo’s readout as a barometer for Corbus’ pipeline asset — the company has said it planned to start a Phase 1 study next year. Corbus’ shares had risen 755% year-to-date, making it one of the best-performing biotech stocks until this point in 2024. “Overall, this update disappoints on both efficacy and safety,” TD Cowen analyst Michael Nedelcovych wrote in a note. “Novo sees a path forward, but potential of this early-stage asset is diminished.” Novo said it will move into a Phase 2b study next year that will include more patients and will test the drug for a longer duration. The drug, also known as INV-202, is also being studied in diabetic kidney disease. That trial completed last month, according to the federal trials database. A first generation of CB1 drugs was marred by safety in the 2000s, and a marketed drug was pulled in Europe because of suicidality concerns. The drug never made it onto the US market. But Novo and other drugmakers, including Corbus and Skye Bioscience, are trying to tackle the class with medicines that don’t penetrate the brain nearly as much, hoping to stave off those safety scares. “We’re taking a new approach, a more profound approach on the biology, and we’re staying out of the brain so that we don’t cause the depressive mood disorders that came with the other ones,” former Inversago CEO François Ravenelle told Endpoints last year. The Novo drug isn’t in the clear on the safety front, though. Anxiety, irritability and sleep disturbances were “more frequent and dose dependent with monlunabant compared to placebo,” Novo said. Those side effects were also mild to moderate, it said. Gastrointestinal side effects were the most common adverse events in the Phase 2a study. The “vast majority” were mild to moderate, the drugmaker said. “The phase 2a results indicate the weight-lowering potential of monlunabant and that further work is needed to determine the optimal dosing to balance safety and efficacy,” Novo’s head of development Martin Holst Lange said in a press release.

Today, a brief rundown of news from Sanofi and Novo Nordisk, as well as updates from The Lasker Foundation, Edgewise Therapeutics and Vanda Pharmaceuticals that you may have missed.Novo Nordisk shares fell 6% in Friday trading today after reporting mixed study resultsfrom a Phase 2 trial of a weight-loss drug it acquired in a deal for startup Inversago Pharma last year. According to Novo, people who received the lowest dose of the drug, a new type of medicine blocking the protein receptor CB1, lost an average of just over 7 kilograms of weight after 16 weeks. Higher doses resulted in limited additional weight loss, while drug recipients reported gastrointestinal as well as neuropsychiatric side effects. Novo is planning a larger and longer mid-stage study of the drug, monlunabant, to find the optimal dosing to balance safety and efficacy, said Martin Holst Lange, its executive vice president and head of development, in a statement. Jonathan GardnerSanofi on Friday presented study results the company has claimed could support approval of its experimental drug tolebrutinib in a form of multiple sclerosis. The data showed tolebrutinib helped delay the time to onset of confirmed disability progression by 31% compared to a placebo in people with non-relapsing secondary progressive MS, while also inducing a spike in liver enzymes that Sanofi said can be managed by monitoring patients. Overall, the findings should enable global filings and approvals given [the] current unmet need in that form of MS, wrote Jefferies analyst Peter Welford. Ben FidlerThree scientists whose research led to a new group of widely popular weight-loss drugs have won a Lasker Award, an annual prize given for discoveries that advance medicine and public health. Joel Habener of Massachusetts General Hospital, Svetlana Mosjov of The Rockefeller University and Lotte Bjerre Knudsen of Novo Nordisk were each handed awards for their roles researching and developing the GLP-1 medicines now used to treat diabetes and obesity. The three have introduced a new era of weight management in which GLP-1 based pharmaceuticals promise to dramatically enhance health, the Lasker Foundation said in a Thursday statement. Ben FidlerShares of Edgewise Therapeutics surged nearly 50% after the company on Thursday revealed early study results for a drug its developing for a form of heart failure. Though only from a small number of healthy volunteers in a Phase 1 trial and people with hypertrophic obstructive cardiomyopathy in a mid-stage study, the data clearly differentiates Edgewises drug from Bristol Myers Squibbs Camzyos and Cytokinetics aficamten, wrote Leerink Partners analyst Joseph Schwartz. Edgewise dosed the first participants in the next part of its Phase 2 study and expects to report findings next year.Ben FidlerThe Food and Drug Administration on Thursday declined to approvea Vanda Pharmaceuticalsdrug called tradipitantfor symptoms of gastroparesis. Vanda claimed the agency generally disregarded the evidence from two placebo-controlled trials and requested additional studies with a design and duration that are “inconsistent with the advice of key experts“ in the field. The company still plans to pursue an approval in gastroparesis, and intends to file a separate application for use preventing vomiting and motion sickness. Delilah AlvaradoThe House Energy and Commerce Committee voted unanimously Wednesday to support legislation extending the pediatric rare disease voucher program for another six years, to 2030. The program, which was due to expire on Sept. 30, grants companies that win approvals of medicines for rare pediatric diseases a voucher that speeds up drug reviews and can be sold for cash. As of the end of April,the FDA had awarded 53 vouchers since the programs inception in 2012, according to the National Organization for Rare Disorders. Jonathan Gardner '