Bristol Myers Squibb’s examination into whether its heart med Camzyos can spark improvements in patients with non-obstructive hypertrophic cardiomyopathy (nHCM) turned out to be a conclusive failure, leaving the company with one fewer avenue to boost the drug's long-term growth trajectory.

The Camzyos maker initiated the “largest and longest-duration study” to date in patients with nHCM to see if its drug could offer the same benefits as it does in obstructive HCM (oHCM). 

While the trial, dubbed ODYSSEY-HCM, ultimately missed both of its dual primary endpoints, the findings “help us understand that obstructive HCM and non-obstructive HCM are two unique diseases," Milind Desai, M.D., director of the HCM center at the Cleveland Clinic, explained in Bristol's April 14 press release. 

This indicates that new ways of thinking about potential treatment approaches are needed for those with nHCM, Desai added.

HCM is a common heart disease that's often inherited, according to the American Heart Association. In nHCM, the thickened heart muscle that hallmarks HCM doesn’t block the blood flow out of the heart, as is the case with oHCM. 

In 2022, Camzyos won FDA approval to treat certain patients with oHCM. 

BMS hadn’t given much fanfare to its drug's potential expansion into nHCM leading up to the readout, although the ODYSSEY-HCM was listed as a potential catalyst on the company’s rundown of key milestones at this year’s J.P. Morgan Healthcare Conference.

With looming losses of exclusivity for a handful of key blockbusters, the Camzyos miss in nHCM could add pressure onto other upcoming growth catalysts for BMS, BMO Capital Markets analyst Evan Siegerman pointed out in a recent note to clients.

At the same time, the trial miss does not affect Camzyos' outlook in obstructive HCM, since there were no new safety signals flagged in the latest results, Siegerman noted.

The company didn’t offer much further insight on the trial failure but said it will share detailed results in the future, leaving analysts to wonder whether the issues were specific to Camzyos and the ODYSSEY-HCM trial design or point to a larger issue within the drug class.

BMS’ declaration that oHCM and nHCM are two unique diseases led William Blair analysts to believe that the study wasn’t a “near-miss," the team wrote in a recent note to clients, suggesting that the trial’s failure may be more attributable to differences in disease biology than the drug itself.

If true, that could spell trouble for Cytokinetics, which is testing its own drug aficamten in nHCM. Aficamten uses the same mechanism of action as Camzyos, meaning that there’s a chance BMS’ failure in the disease could “read through to the class,” William Blair analysts noted.

However, Evercore ISI analysts pointed out a few differences in BMS and Cytokinetics’ trial designs that could potentially favor the latter, such as a single endpoint on Cytokinetics' study. While it's “tough to conclude” if BMS’ issues will hamper the wider drug class, Camzyos dropping out of the nHCM race would give Cytokinetics a bigger piece of the market if its candidate proves successful, according to the Evercore analysts. Aficamten is up for a September FDA approval decision in oHCM.

According to the Evercore ISI team, nHCM studies are often seen as a “dry run” for a much larger market opportunity in heart failure with preserved ejection fraction (HFpEF).  BMS is evaluating a different cardiac myosin inhibitor, known as MYK-224, in this indication after a phase 2 proof of concept study using Camzyos generated preliminary efficacy and safety data that gave the company enough confidence to advance its development program for MYK-224 in HFpEF, a BMS spokesperson explained in an emailed statement. 

Camzyos brought in $602 million last year, a 161% jump from the prior year. BMS has projected the drug could generate $4 billion in potential peak sales.