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Bristol Myers Squibb announced that mavacamten did not achieve statistical significance in meeting the dual primary endpoints in the Phase 3 ODYSSEY-HCM trial for patients with symptomatic non-obstructive hypertrophic cardiomyopathy (HCM). However, the study reported no new safety concerns related to the drug.

“The ODYSSEY-HCM trial, the largest and longest-duration study completed to date in patients with non-obstructive HCM, tested the hypothesis of whether a cardiac myosin inhibitor would improve measures of feel and function for these patients, showing clinical benefits similar to what we have seen in obstructive HCM,” said Milind Desai, MD, MBA, Vice Chair in the Heart, Vascular & Thoracic Institute and Director of the HCM Center, Cleveland Clinic. “The findings of this trial help us understand that obstructive HCM and non-obstructive HCM are two unique diseases. Through long-term trials and real-world data from thousands of patients with symptomatic obstructive HCM, we have seen the meaningful impact that Camzyos has on improving the quality of life for patients living with this condition. ODYSSEY-HCM indicates that we must consider new ways of thinking about potential treatment approaches for non-obstructive HCM. We want to thank the patients and investigators for their efforts in completing this important trial and their commitment to advancing the scientific understanding of this complex disease.”

“While these results are disappointing, the ODYSSEY-HCM trial meaningfully contributes to the understanding of non-obstructive HCM, a disease where there remains a significant need for new treatment options,” said Roland Chen, MD, senior vice president, drug development, Immunology and Cardiovascular Medicines, Bristol Myers Squibb. “These findings represent the first Phase 3 clinical trial data for a cardiac myosin inhibitor in non-obstructive HCM. Importantly, these results do not change the favorable 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.”

Bristol Myers Squibb will work with key investigators to share detailed results with the scientific community in the future.

Bristol Myers Squibb thanks the patients and investigators who participated in the ODYSSEY-HCM clinical trial.

About ODYSSEY-HCM

ODYSSEY-HCM is a Phase 3 randomized, double-blind, placebo-controlled trial that enrolled 580 adult patients with symptomatic (NYHA class II or III) non-obstructive hypertrophic cardiomyopathy (nHCM) worldwide.

The dual-primary endpoints for the trial were to examine changes from baseline in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-23 CSS) and peak oxygen consumption (pVO2) at Week 48. Secondary endpoints included 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) at Week 48.

About CAMZYOS® (mavacamten)

CAMZYOS® (mavacamten) is the first and only cardiac myosin inhibitor approved in the U.S., indicated for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (oHCM) to improve functional capacity and symptoms, and in the European Union, indicated for the treatment of symptomatic (NYHA, class II-III) oHCM in adult patients. It has also received regulatory approvals in more than 50 countries and regions across five continents. CAMZYOS is a selective, reversible, allosteric inhibitor of cardiac myosin. CAMZYOS modulates the number of myosin heads that can enter “on actin” (power-generating) states, thus reducing the probability of force-producing (systolic) and residual (diastolic) cross-bridge formation. Excess myosin actin cross-bridge formation and dysregulation of the super-relaxed state are mechanistic hallmarks of HCM. CAMZYOS shifts the overall myosin population towards an energy-sparing, recruitable, super-relaxed state. In oHCM patients, myosin inhibition with CAMZYOS reduces dynamic left ventricular outflow tract (LVOT) obstruction and improves cardiac filling pressures. These effects on the heart translate to improvement in symptoms and ability to be active in symptomatic patients with oHCM.

A marker linked to inflammation, C-reactive protein, may increase significantly during the follicular phase of the menstrual cycle in female patients with sickle cell disease (SCD), according to emerging research published today in Blood Vessels, Thrombosis & Hemostasis. This observation provides insight into the pattern of painful vaso-occlusive events (VOEs), which are driven by inflammation, in female patients with the disorder.

“We know both from the literature and anecdotally from our patients that women with SCD have VOEs that cluster around their menstrual periods. We wanted to examine the potential reason behind that,” said the study’s lead author, Jessica Wu, MD, a resident physician in the Department of Obstetrics and Gynecology at the Perelman School of Medicine at the University of Pennsylvania. “Our study is the first to examine the association between menstrual cycles and inflammation in female patients with SCD.”

“The menstrual cycle is often overlooked in research and clinical care, but can interact with health in important ways, as we are seeing in SCD,” said the study’s principal investigator, Andrea Roe, MD, MPH, an assistant professor of obstetrics and gynecology at the Perelman School of Medicine at the University of Pennsylvania. Dr. Wu, Dr. Roe, and their colleagues analyzed plasma samples in the Penn Medicine BioBank repository from individuals with a confirmed SCD diagnosis. After excluding samples from participants who were pregnant, hospitalized with a VOE, or treated at an emergency department or infusion center at the time of sample collection, 31 plasma samples were included in their analysis – 13 from female patients and 18 from male patients.

SCD, the most common inherited red blood cell disorder in the United States, is characterized by abnormally shaped blood cells. These cells can become lodged in the veins and block blood flow, leading to organ damage, infection, and episodes of severe pain throughout the body, known as VOEs, which can be so debilitating that people seek treatment at a hospital. Previous literature has shown that female patients with SCD have more frequent, severe VOEs, often around the time of their menstrual periods.

The researchers measured C-reactive protein in all samples and female sex hormones, including estradiol, progesterone, and luteinizing hormone, in samples from female patients. They compared C-reactive protein, clinical laboratory markers, and other biomarkers by patient sex, SCD genotype, hydroxyurea, and, in the cases of the 13 female patients, made the same comparisons between samples from the follicular and luteal phases of the menstrual cycle. A progesterone level of 1.75 ng/mL was used to define the occurrence of ovulation and cutoff between the follicular and luteal phases.

Among the 31 samples, the average concentration of C-reactive protein was 4.45 mg/L, with no significant differences observed based off SCD genotype or treatment with hydroxyurea. When Dr. Wu and her colleagues compared C-reactive protein between samples from female patients and male patients, they observed no significant difference (3.88 vs. 4.45 mg/L, p=0.89); however, when they compared C-reactive protein between samples taken during the follicular or luteal phases of the female patients, they observed higher median C-reactive protein in the follicular phase versus the luteal phase (8.80 vs. 0.82 mg/L, p=0.03).

“The amount of inflammation is significantly elevated in the follicular phase, or first half, of the menstrual cycle in female patients with SCD,” said Dr. Wu. “This observation correlates with what we see in the literature, that this is the time in which this patient population has the most VOEs.”

These results also mirror the trend seen in the menstrual cycles of the general population, though the magnitude of elevation is much greater in female patients with SCD than in those without SCD during the follicular phase (8.80 mg/L vs. 0.74 mg/L). The significant fluctuation of C-reactive protein in female patients with SCD could have clinical implications given the similar temporal pattern of VOEs, providing a target for intervention.

“Many hormonal contraceptives can suppress menstruation or suppress the hormone fluctuations that occur from cycle to cycle, so contraceptives could help these patients manage their pain crises,” said Dr. Wu. “SCD is a really debilitating and painful disease. The more data we have about how it presents in female patients, the better we can counsel them on anticipating and managing their pain.”

Dr. Wu cautioned that this research is still early and has several limitations, including its small sample size and cross-sectional, retrospective nature. Specifically, since each sample was from a singular time point in different individuals, menstrual phase comparisons in C-reactive protein (follicular vs. luteal phase) were unable to be performed within the same individual. Additionally, because VOEs evolve through different stages, the researchers could not confirm that the subjects were at their baseline inflammatory levels, even if they did not have symptoms of an acute VOE.

The researchers intend to validate their findings through further prospective studies with larger sample sizes and plan to explore menstrual patterns of other biomarkers associated with SCD, as well as correlation with clinical symptoms. 

Reference:

Jessica Wu, Veronica Bochenek, Kandace Gollomp, Andrea H. Roe, C-reactive protein and the menstrual cycle in females with sickle cell disease, Blood Vessels, Thrombosis & Hemostasis, 2025, https://doi.org/10.1016/j.bvth.2025.100067.

South Korea: New data on 5α-reductase inhibitors (5-ARIs) reveals that low cumulative doses are associated with an increased risk of suicide but a decreased risk of cardiovascular mortality in patients with benign prostatic hyperplasia (BPH) or androgenic alopecia (AGA).

A study led by researchers at Mass General Brigham suggests that, when it comes to cardiovascular health, food timing could be a bigger risk factor than sleep timing

Numerous studies have shown that working the night shift is associated with serious health risks, including to the heart. However, a new study from Mass General Brigham suggests that eating only during the daytime could help people avoid the health risks associated with shift work. Results are published in Nature Communications.

“Our prior research has shown that circadian misalignment – the mistiming of our behavioral cycle relative to our internal body clock – increases cardiovascular risk factors,” said senior author Frank A.J.L. Scheer, PhD, a professor of Medicine and director of the Medical Chronobiology Program at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. “We wanted to understand what can be done to lower this risk, and our new research suggests food timing could be that target.”

Animal studies have shown that aligning food timing with the internal body clock could mitigate the health risks of staying awake during the typical rest time, which prompted Scheer and his colleagues to test this concept in humans.

For the study, researchers enlisted 20 healthy young participants to a two-week in-patient study at the Brigham and Women’s Center for Clinical Investigation. They had no access to windows, watches, or electronics that would clue their body clocks into the time. The effect of circadian misalignment could be determined by comparing how their body functions changed from before to after simulated night work.

Study participants followed a “constant routine protocol,” a controlled laboratory setup that can tease apart the effects of circadian rhythms from those of the environment and behaviors (e.g., sleep/wake, light/dark patterns). During this protocol, participants stayed awake for 32 hours in a dimly lit environment, maintaining constant body posture and eating identical snacks every hour. After that, they participated in simulated night work and were assigned to either eating during the nighttime (as most night workers do) or only during the daytime. Finally, participants followed another constant routine protocol to test the aftereffects of the simulated night work. Importantly, both groups had an identical schedule of naps, and, thus, any differences between the groups were not due to differences in sleep schedule.

The investigators examined the aftereffects of the food timing on participants’ cardiovascular risk factors and how these changed after the simulated night work. Researchers measured various cardiovascular risk factors, including autonomic nervous system markers, plasminogen activator inhibitor-1 (which increases the risk of blood clots), and blood pressure.

Remarkably, these cardiovascular risk factors increased after simulated night work compared to the baseline in the participants who were scheduled to eat during the day and night. However, the risk factors stayed the same in the study participants who only ate during the daytime, even though how much and what they ate was not different between the groups-only when they ate.

Limitations of the study include that the sample size was small, although of a typical size for such highly controlled and intensive randomized controlled trials. Moreover, because the study lasted two weeks, it may not reflect the chronic risks of nighttime versus daytime eating.

A strength is that the study participants’ sleep, eating, light exposure, body posture, and activity schedule were so tightly controlled.

“Our study controlled for every factor that you could imagine that could affect the results, so we can say that it’s the food timing effect that is driving these changes in the cardiovascular risk factors,” said Sarah Chellappa, MD, MPH, PhD, an associate professor at the University of Southampton, and lead author for the paper.

While further research is necessary to show the long-term health effects of daytime versus nighttime eating, Scheer and Chellappa said the results are “promising” and suggest that people could improve their health by adjusting food timing. They add that avoiding or limiting eating during nighttime hours may benefit night workers, those who experience insomnia or sleep-wake disorders, individuals with variable sleep/wake cycles, and people who travel frequently across time zones.

Reference:

Chellappa, S.L., Gao, L., Qian, J. et al. Daytime eating during simulated night work mitigates changes in cardiovascular risk factors: secondary analyses of a randomized controlled trial. Nat Commun 16, 3186 (2025). https://doi.org/10.1038/s41467-025-57846-y