FDA delays its decision on Bristol Myers' $13B heart drug another three months
Last week, Bristol Myers Squibb marched out long-term data for its heart drug mavacamten ahead of what execs had hoped would be a positive FDA decision in January. But regulators are saying they need a bit more time to think.
The FDA has extended mavacamten’s PDUFA date three months, from Jan. 28 to April 28, Bristol Myers announced on Friday. The news came just a few days after independent drug pricing watchdog ICER raised concerns about the candidate’s long-term safety in its final evidence report.
Mavacamten, a myosin inhibitor, was the centerpiece of BMS’ $13 billion MyoKardia buyout last October. The pharma giant’s shooting for an initial indication in symptomatic obstructive hypertrophic cardiomyopathy, or oHCM: a condition in which the muscular wall between the two bottom chambers of the heart becomes thicker than normal, blocking blood flow out of the heart.
In an abstract at the American Heart Association conference, BMS said HCM patients who took mavacamten saw a “sustained reduction” of a hormone called NT-proBNP through Week 48. Higher than normal NT-proBNP levels are indicative of heart failure.
However, the company reported that nine patients paused treatment because their left ventricular ejection fractions (a measurement of how much blood is being pumped out of the heart’s left ventricle) were too low. Eight of the patients resumed treatment at a lower dose after recovery, while one discontinued the trial permanently, the company said.
BMS says the FDA requested more time to “review information pertaining to updates to the proposed Risk Evaluation Mitigation Strategy (REMS),” and that no additional data or studies have been requested.
Mizuho’s Salim Syed speculated that the delay seems to be molecule-specific, and not class-specific, noting that no patients saw EF below 40% in Cytokinetics’ Phase II study for its myosin inhibitor aficamten (also known as CK-274). In that drug’s dose-range finding trial, one patient experienced a transient decrease in LVEF that required dose adjustment, but not dose interruption, Cytokinetics said.
Ejection fraction is considered normal if it’s in the range of 50% to 70%. Of the seven mavacamten patients who experienced EF below 50% in the Phase III EXPLORER-HCM trial, one patient had an EF below 40%.
“This is the primary reason we believe the REMS is molecule-specific and should be treated as such — these are clearly two different safety datasets,” Syed said in a note to investors on Friday. “The PDUFA delay should also be helpful toward enrolling US patients in CK-274’s Ph3 SEQUOIA-HCM study, where ‘start-up activities’ are ‘underway.’
While ICER noted that mavacamten may deliver important benefits for HCM patients with fewer side effects than other drugs, the organization suggested more data are necessary to assess long-term safety:
While mavacamten improved physiologic parameters and symptoms in the EXPLORER trial, the available data are mostly short term, and symptomatic HOCM, once it appears, can last a lifetime. Clinical experts differed on whether the reductions in ejection fraction with mavacamten reflected beneficial improvements in cardiac function, including healthy remodeling, or worrisome changes that could be associated with clinical harm with longer observation times.
Bristol Myers remains confident in the drug, with CMO Samit Hirawat stating: “We look forward to continuing to work closely with the FDA to bring this important medicine to patients.”