MyoKardia is headed for its biggest moment since debuting as a publicly traded company in 2015. Forthcoming results from a Phase 3 study of its heart disease treatment mavacamten will be an inflection point, as the California-based biotech will either have a drug ready to submit for an approval, or will be contemplating several more years of unprofitable clinical development.
The company is due to disclose the data sometime this quarter, as study investigators completed the final patient visits from the 30-week trial in March. MyoKardia said the study, called EXPLORER, hasn't been disrupted by the COVID-19 pandemic, although patient enrollment into an extension phase has been suspended.
Mavacamten is MyoKardia's most advanced project, and failure of the EXPLORER trial would add years to its timeline for achieving approval and launch of a drug. Moreover, a setback could cause investors to shy away from the company, as its two other experimental drugs in clinical testing act via the same biological pathway as mavacamten.
EXPLORER tested mavacamten in hypertrophic cardiomyopathy, or HCM, a usually inherited heart condition in which cardiac muscles become thickened and can't pump blood as well as healthy tissue. EXPLORER enrolled patients with the obstructive form of the disorder, in which the thickening reduces the amount of blood that can be pumped from the heart's left ventricle.
HCM bears some similarity to heart failure, in which the heart also is unable to pump enough blood due most often to cardiovascular damage. Heart failure affects around 7 million people in the U.S., according to the Centers for Disease Control and and Prevention. By contrast, about 700,000 suffer from HCM, per the Hyptertophic Cardiomyopathy Association.
The biggest branded drug in heart failure is Novartis' Entresto, which recorded sales of $1.7 billion in 2019. But it's taken the Swiss company four years, and stepped-up investments in marketing, to get Entresto to its current level, underscoring the challenges drugmakers face in the market for cardiovascular disease medicines.
Compared with heart failure, HCM has "a very mild clinical course, a fraction of patients have symptoms, and most can be managed," Ethan Weiss, an associate professor at the University of California-San Francisco medical school, wrote in an email to BioPharma Dive.
MyoKardia's hypothesis is that by improving the heart muscles' ability to relax, mavacamten can ease symptoms and improve the heart's pumping power. The drug does so by inhibiting a protein called myosin, which plays a key role in muscle contraction.
To succeed in EXPLORER, mavacamten will need to show significantly more patients responded to treatment as defined by an improvement in peak oxygen consumption, than did those on placebo.
Specifically, a "responder" will be defined as the study participants who improved by one grade on the New York Heart Association's (NYHA) heart failure scale and experienced an increase in the max amount of oxygen they can use during when exercising — a measurement known as VO2 max — or those who saw an even larger increase in oxygen uptake with no worsening in NYHA classification.
The response criteria may not necessarily show patients have improved, however, Weiss said. "For the increase in VO2 max with improved NYHA class, that is something patients would notice. Almost by definition they would not notice if there is no change in functional class," he said.
At the virtual meeting of the American College of Cardiology on March 30, the company revealed data from a Phase 2 trial called MAVERICK in non-obstructive disease that showed patients taking mavacamten had statistically significant reductions in markers that indicate heart stress and damage.
Alethia Young, an analyst at investment firm Cantor Fitzgerald, said MAVERICK, among other trials, should lend confidence that EXPLORER will be a success.
"We think that there is enough evidence among preclinical, early, and open label studies and now MAVERICK that mavacamten is active in this disease," she wrote in a March 31 note to clients.
MyoKardia had partnered the drug with Sanofi, but the Paris-based pharmaceutical company pulled out of a four-year deal in January 2019 after spending $230 million on mavacamten research. MyoKardia said Sanofi withdrew because it wanted more commercial rights in the U.S., a request MyoKardia didn't want to grant.
MyoKardia subsequently raised $271 million in March 2019, an amount it said was sufficient to fund trials, regulatory submission and commercial preparations. As of Dec. 31, the company had $101 million in cash and $329 million in investments.
In the event of success in EXPLORER, Young sees the potential for shares in MyoKardia to increase to $100 a share, up from the $50.15 the stock reached at market close April 8. If the trial fails, company shares might be trade as low as $10 apiece, Young wrote.