Bristol Myers Squibb currently has the only drug approved specifically for treating obstructive hypertrophic cardiomyopathy, a debilitating disorder that can progress to heart failure. But safety risks and restrictions on this drug still leave an unmet patient need, one that a growing number of biotechs are vying to fill.
Braveheart Bio is developing a drug whose clinical data to date show the potential for advantages in safety along with greater patient and physician convenience. San Francisco-based Braveheart is preparing to advance its in-licensed molecule to Phase 3 testing and on Wednesday, the startup unveiled $185 million for this global clinical trial on track to begin in 2026.
In obstructive hypertrophic cardiomyopathy, or oHCM, heart muscle becomes thicker, making it harder for the organ to pump blood. Standard treatments include older drugs that were not developed for oHCM, such as blood pressure-lowering beta blockers and calcium channel blockers. Those drugs do not address the underlying cause of the thickening, which comes from excessive contractions driven by mutated versions of a heart muscle protein called myosin.
Braveheart’s drug, BHB-1893, is an oral small molecule myosin inhibitor. Blocking this target has clinical and regulatory validation from BMS’s Camzyos, which in 2022 became the first myosin inhibitor approved by the FDA for treating oHCM. But this drug, projected to become a blockbuster seller, also has the effect of reducing left ventricular ejection fraction (LVEF), which is how much blood the left ventricle pumps with each contraction. Reduced LVEF can contribute to heart failure, a risk flagged in a black box warning on the Camzyos label. Because of this risk, Camzyos is available only through a risk evaluation and mitigation strategy (REMS), a program for monitoring and managing potential complications.
Travis Murdoch, Braveheart’s CEO, says BHB-1893 could have a safety edge. The obstruction of blood flow in oHCM leads to a high gradient, a measure of how much force is needed to pump blood. A high gradient means the heart must work harder. As a class, myosin inhibitors reduce gradient. But Murdoch said BHB-1893’s data show the potential to be best in class.
“We’re seeing very dramatic reductions in gradient,” Murdoch said. “On the Phase 1 data, all patients achieved what would be considered a complete gradient response within a matter of a few days. And so that really, we think, points to potential for greater efficacy that needs to be translated and seen in further clinical studies.”
The Phase 1 data were presented during the European Society of Cardiology Congress in September. Soon after, Hengrui Pharma, the Shanghai-based company that discovered and developed the molecule, announced Braveheart licensed global rights to the drug, excluding China, Hong Kong, Macao, and Taiwan. Murdoch said his company has also seen encouraging Phase 2 results, but those data remain confidential. Hengrui is currently evaluating the drug, which it calls HRS-1893, in a Phase 3 test in China.
BHB-1893’s data to date indicate a wider safety margin before adverse effects emerge, Murdoch said. That margin could avoid the safety risks and REMS program that come with Camzyos. The REMS for Camzyos requires echocardiogram assessments of LVEF before and during treatment. Murdoch, a gastroenterologist, said patients taking BHB-1893 achieve a steady state, the concentration of medication in the body consistently in the therapeutic range, within about a week. Achieving a steady state sooner simplifies dose titration, making BHB-1893 a potentially more tunable drug, he said.
“That’s important from the point of view of how and when physicians will use medications in this class because more complicated titration, with a lot of echocardiograms, is quite burdensome on the [healthcare] system,” Murdoch said.
Murdoch declined to specify the molecular attributes of BHB-1893 that make it a potentially better drug, saying those details remain undisclosed. But he said BHB-1893’s pharmacology appears different, which is supported by the clinical trial results to date. Braveheart is also developing this molecule for the less common non-obstructive HCM, which could offer further differentiation from the BMS drug. In April, Camzyos failed a Phase 3 test in this indication despite positive trends for many biomarkers. Murdoch said those results suggest a different molecule with a different profile could be successful.
Murdoch was most recently CEO of Human Immunology Biosciences (HI-Bio), an autoimmune disease drug developer. Last year, Biogen paid more than $1.1 billion to acquire the clinical-stage startup as part of its pipeline diversification strategy. Murdoch continued to lead the HI-Bio team under Biogen, but over the summer, the investment firms that formed Braveheart persuaded him to join. Murdoch said the firms spent a year searching globally for cardiovascular assets and BHB-1893 rose to the top.
The investors in Braveheart’s Series A financing include Andreessen Horowitz, Forbion, OrbiMed, Enavate Sciences, and Frazier Life Sciences. Biogen CEO Chris Viehbacher is chair of Braveheart’s board of directors. Braveheart paid $75 million to license BHB-1893; Hengrui could receive up to $1 billion in milestone payments tied to the progress of the drug.
Startups developing drugs for non-obstructive HCM include Haya Therapeutics and Imbria Pharmaceuticals. An oHCM drug could reach patients soon. An FDA ruling on aficamten, a cardiac myosin inhibitor developed by Cytokinetics, is expected by Dec. 26. This drug was initially slated to receive a regulatory decision in May, but the FDA told Cytokinetics it needed more time to review the proposed REMS for the drug. Like Braveheart, Cytokinetics sees safety as key to distinguishing its drug from BMS’s obstructive HCM product.
“We believe the commercial prospects of aficamten are highly dependent on whether FDA approves aficamten with a label and REMS that are less challenging to prescribers and patients than the REMS applicable to Camzyos,” Cytokinetics said in its most recent quarterly report.
Magicmine, Getty Images
