MyoKardia, Inc.

iStock, apfDesign According to analysts at BMO Capital Markets, non-obstructive hypertrophic cardiomyopathy would have meant a $1.3 billion label expansion opportunity for Camzyos. Bristol Myers Squibb ’s myosin blocker Camzyos failed to ease clinical burden and improve oxygen consumption in patients with non-obstructive hypertrophic cardiomyopathy, the pharma announced on Monday. “This trial failure removes the opportunity for Camzyos in the 1/3 HCM patients who have the non-obstructive form of the disease,” analysts at BMO Capital Markets told investors in a Monday note. The late-stage stumble makes Camzyos’ label expansion into non-obstructive HCM “highly unlikely,” the analysts said. BMS did not present specific data in the news release, only revealing that Camzyos “did not meet its dual primary endpoints” in the Phase III ODYSSEY-HCM study, including 48-week improvement in peak oxygen consumption and other symptoms, including shortness of breath and blood markers for potential heart failure. In terms of safety, BMS did not document any new signals of concern. The pharma has promised to share detailed results from ODYSSEY-HCM “in the future,” as per its Monday release. Hypertrophic cardiomyopathy is a genetic disorder that causes heart muscle thickening. Depending on whether that thickening reduces flow of blood from the heart, the disorder can be classified as obstructive or non-obstructive. For BMO, the failure did not come as a big surprise: “We’ve always framed this trial as more challenging.” The analysts pointed to the difficulties of demonstrating strong and significant treatment benefits in patients with the less severe, non-obstructive form of the disease. Camzyos is an orally available cardiac myosin inhibitor that works by protein actions in muscular activation in the heart, with the goal of relaxing heart muscle and allowing the heart to fill with more blood. BMS gained ownership of Camzyos when it bought MyoKardia for $13.1 billion in October 2020. Two years later, the pharma secured the FDA’s approval for the drug, allowing its use in obstructive HCM. According to the BMO note, ODYSSEY-HCM will not change Camzyos’ opportunity in obstructive HCM, retaining a roughly $2.7 billion sales potential at peak. Still, the late-stage failure is a blow to BMS’ cardio portfolio, which will now miss out on more an additional 33,000 patients with the non-obstructive form of the disease—approximately $1.3 billion in earnings. BMO called this missed opportunity “meaningful.” BMS in the meantime is continuing to beef up its pipeline, with multiple “impactful catalysts” still lined up for 2025, according to BMO. “Top of mind for us remain the ARISE data evaluating the use of Cobenfy in adjunctive schizophrenia,” the analysts wrote, adding that this readout will come “any day now.” BMO is also looking forward to Cobenfy data in Alzheimer’s psychosis, expected in the latter half of 2025.

Dive Brief:Bristol Myers Squibb on Monday said its drug Camzyos failed a Phase 3 trial in people with a progressive heart condition, closing off an opportunity to expand use of a medicine it sees as a future blockbuster.According to Bristol Myers, Camzyos missed the dual main goals of a study focused on the non-obstructive form of HCM, or hypertrophic cardiomyopathy. It failed to meaningfully improve peak oxygen consumption as well as scores on an assessment of heart health. The company didnt provide study details, but said more information will be shared with the scientific community in the future.Camzyos was acquired through the $13 billion buyout of MyoKardia in 2020 and two years later became the first drug cleared for use in the obstructive and more common form of the disease. Biotechnology companies Cytokinetics and Edgewise Therapeutics are developing similar medicines that are both in the advanced stages of clinical testing. Cytokinetics drug, aficamten, could be approved in the U.S. later this year.Dive Insight:Camzyos setback carries implications for Bristol Myers as well as the companies trying to develop better medicines for HCM, a chronic condition characterized by a potentially deadly stiffening of the heart muscle.Bristol Myers is bracing for the losses of billions of dollars in yearly revenue when the patents expire for its cancer immunotherapy Opdivo and blood thinner Eliquis. The company already announced a cost-cutting plan under CEO Chris Boerner, and is looking to a handful of medicines, Camzyos among them, to grow sales in the years ahead.Camzyos generated $602 million in sales in 2024. But Bristol Myers has said that number could reach $4 billion in 2029, and one way to get there was a clearance in the non-obstructive setting, which is estimated to account for about a third of the people with the condition. The setback is a disappointment, wrote Leerink Partners analyst David Risinger, though Bristol Myers could rebound if a series of coming Phase 3 readouts are successful.The study failure also stirred debate among analysts as to whether drugs like Camzyos, known as cardiac myosin inhibitors, can help all people with HCM. Camzyos has proven beneficial for the obstructive form that impedes blood flow and can lead to heart failure as well as other potentially serious complications. The non-obstructive type doesnt, but can still put people at risk of poor health outcomes. The new study tested whether Camzyos might be similarly helpful for those people as well.The fact that Camzyos wasnt suggests obstructive and non-obstructive HCM are two unique diseases, said Milind Desai, the director of the Cleveland Clinics HCM Center, in a statement provided by Bristol Myers.Analysts were mixed on whether the cardiac myosin inhibitors Cytokinetics and Edgewise are developing might similarly struggle in non-obstructive HCM. Cytokinetics drug, aficamten, is under Food and Drug Administration review in obstructive HCM and in a Phase 3 trial in non-obstructive disease. Edgewises EDG-7500 could join it in late-stage testing next year.Matt Phipps, of the investment bank William Blair, wrote that Camzyos shaky performance in the latest study as well as Phase 2 testing in non-obstructive HCM patients may be more attributed to disease biology, which has negative implications for the whole drug class.That form of the disease is also more heterogeneous, making it tougher for a drug to succeed in testing, added RBC Capital Markets Leonid Timashev.Still, there are key differences between the drugs and their development plans that leave some analysts optimistic about Cytokinetics and Edgewises chances. Aficamten appeared to perform better in earlier testing in non-obstructive patients, and Cytokinetics Phase 3 study is designed differently, wrote Mizuho Securities Salim Syed. RBCs Timashev added that EDG-7500s unique mechanism could overcome the limitations of other medicines in non-obstructive HCM.We now see a 2-handed market split between Cytokinetics and Edgewise, Timashev wrote. '

Bristol Myers Squibb will utilise the programme to assess the Cell Shuttle platform as an automated manufacturing process. Credit: Tada Images/Shutterstock.com. Bristol Myers Squibb’s (BMS) Phase III trial investigating Camzyos (mavacamten) in patients with non-obstructive hypertrophic cardiomyopathy (nHCM) has failed to meet its dual primary endpoints. In the ODYSSEY-HCM (NCT05582395) trial, the cardiac myosin inhibitor did not show a benefit compared to placebo in either the Kansas City Cardiomyopathy Questionnaire – Clinical Summary Score (KCCQ-23 CSS) or peak oxygen consumption (pVO2) after 48 weeks. The study was a Phase III randomised, double-blind, placebo-controlled study that enrolled 580 adult patients with symptomatic (NYHA class II or III) nHCM. The company has not mentioned the status of secondary endpoints, which evaluated a change from baseline in ventilatory efficiency (VE/VCO2), NYHA functional class, N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and the Hypertrophic Cardiomyopathy Symptom Questionnaire-Shortness of Breath (HCMSQ-SoB) after 48 weeks. Dr. Roland Chen, senior vice president, drug development, immunology and cardiovascular medicines at BMS, said: “These findings represent the first Phase III clinical trial data for a cardiac myosin inhibitor in non-obstructive HCM. Importantly, these results do not change the favourable benefit-risk profile that has been consistently demonstrated across our Camzyos clinical trials in obstructive HCM and the robust body of real-world effectiveness and safety evidence showing its benefit for people living with obstructive HCM around the world.” This Phase III failure comes as a blow to BMS, which was hoping to gain label expansion for the drug’s use in nHCM. Camzyos gained approval from the US Food and Drug Administration (FDA) in 2022 as a treatment for obstructive forms of HCM and remains the only FDA-approved treatment for that condition. European approval followed in June 2023 . The therapy was the main asset that inspired BMS’ acquisition of MyoKardia for $13bn in 2020. Despite having held its spot as the only HCM therapy for nearly three years, BMS is gearing up for its first potential competition in the space as the FDA has accepted a marketing application by Cytokinetics for its therapy aficamten for treating obstructive HCM. Investigators said the Phase III trial results make them believe HCM and nHCM should be classified as different diseases. Dr. Milind Desai, vice chair of the Heart, Vascular & Thoracic Institute at the Cleveland Clinic said: “The findings of this trial help us understand that obstructive HCM and non-obstructive HCM are two unique diseases. ODYSSEY-HCM indicates that we must consider new ways of thinking about potential treatment approaches for nHCM.” GlobalData predicts Camzyos will reach blockbuster status next year with a global sales forecast of $2.39bn in 2030. GlobalData is the parent company of Clinical Trials Arena.