Shares of Edgewise Therapeutics and Cytokinetics diverged Wednesday after safety questions stole the limelight from Edgewise's otherwise successful heart disease study.
The two companies are working on treatments for hypertrophic cardiomyopathy. In this condition, the heart muscle becomes thicker than normal, primarily affecting how the left ventricle pumps blood.
Edgewise Therapeutics' drug showed key reductions in how hard the heart has to work to pump blood. It also led to lower levels of biomarker associated with heart failure. But 14% of patients experienced atrial fibrillation, an irregular heartbeat. Two of the four patients needed treatment for it.
Analysts noted atrial fibrillation, often called afib, is expected in patients with this heart disease. But investors hammered Edgewise stock, sending it down 22.9% to 15.52. Cytokinetics, which is nearing Food and Drug Administration approval for its drug, saw shares jump 7.3% to 40.25.
The Benefits Of Edgewise's Drug
In a 28-day study, Edgewise aimed to show its drug could reduce left ventricular outflow gradient, or LVOT-G. This is essentially how hard the left ventricle has to work to pump blood. A higher LVOT-G signals a patient has hypertrophic cardiomyopathy, also called HCM.
Patients with obstructive HCM who received a high dose of Edgewise Therapeutics' EDG-7500, had reductions of 71% and 58%, respectively, at rest and after exercise. They also showed a 62% average decrease in a biomarker associated with heart failure.
Leerink Partners analyst Joseph Schwartz says the LVOT-G reductions trounced late-stage test results from Cytokinetics and Bristol Myers Squibb. Cytokinetics' aficamten and Bristol's approved drug, Camzyos, block cardiac myosin, a protein involved in contracting the heart. Edgewise's drug targets cardiac sarcomere, the contracting structure of the heart.
The other drugs reduced LVOT-G by 50% to 55% around 28 days. Longer term, they had reductions of 60% to 70%.
Side Effects Overshadow Benefits
It's important to note that there's a risk of overtreating HCM by suppressing cardiac function. This causes reduced left ventricular ejection fraction, or LVEF. One patient with obstructive HCM in Edgewise Therapeutics' study showed a lower LVEF and recovered after treatment.
But the bigger safety issue is with atrial fibrillation.
"In principle, a rate of just 14% is well aligned with historical rates in trials and background rates in the population and could be noise," RBC Capital Markets analyst Leonid Timashev said in a report.
But he noted three of the four cases occurred in patients who received the higher dose.
"The fact that two were serious is a complexity that could prompt the FDA to review this closely and could require additional monitoring and/or exclusions, especially in the real world," he said. "Given the efficacy shown at 50 mg as well, we believe there is still likely a sufficient therapeutic window even if 100 mg is deemed not acceptable for use as a starting dose in all patients."
Rivaling Bristol Myers' Camzyos
Timashev kept his outperform ratings on Edgewise Therapeutics and Cytokinetics stocks.
He notes Cytokinetics has a roughly four-year lead time on Edgewise. The FDA is expected to approve Cytokinetics' aficamten for patients with obstructive HCM in September. He sees Edgewise's drug as being more damaging to Bristol Myers' Camzyos, though Bristol stock fell just a fraction.
"We continue to like CYTK given what we believe should be a differentiated profile vs (Camzyos), and believe the company can leverage the more convenient profile (faster titration, less echos, more flexibility) to drive $3.9 (billion) in peak sales and entrench itself ahead of EWTX's launch," he said.
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