TRIALS UNDER DEVELOPMENT
This past year saw significant advances in clinical trials. The Angioma Alliance has already created guidelines used by the medical community to standardize care. But there is great need for safe medications, instead of surgery. The Angioma Alliance is actively preparing patients and creating a network of Clinical Centers where drug trials can be staged. And they are working with drug companies and academic researchers to design drug trials that have the best chance of success. They are undertaking big projects that save lives and improve the quality of care for thousands of CCM patients around the world.
Atorvastatin Trial
The Atrovastatin Trial has just completed enrollmet of Phase I/II at the University of Chicago. The objective is to evaluate the effectiveness of a currently approved and widely used drug, atorvastatin, in stabilizing cerebral cavernous angiomas that have caused a symptomatic bleed, for which a decision was made not to surgically resect the hemorrhagic lesion. Atorvastatin is a statin cholesterol-lowering drug, also used for the prevention of stroke and heart attack. Statins are a class of drugs commonly used to treat high blood pressure. Statins have wide-ranging effects in the body and are known to alter many different chemical signaling systems. Statins inhibit the action of a protein called Rho Kinase (ROCK). In recent years, CCM researchers have shown that inhibiting the action of Rho Kinase (ROCK) may have a potential therapeutic effect on human CCM patients. In mice, statin treatment is able to reduce lesion size, number, and bleeding. These findings have led to the first clinical drug trial for cavernous angioma with symptomatic hemorrhage.
REC-994
REC-994, a potentially first-in-class, orally bioavailable small molecule for the treatment of CCM, is being developed by Recursion Pharmaceuticals specifically for the treatment of symptomatic cerebral cavernous malformations. The Phase I trial of REC-994, using healthy volunteers, was completed in late 2020, where it demonstrated tolerability and suitability for chronic dosing. REC-994 has been granted Orphan Drug designation for CCM by the U.S. Food and Drug Administration and the European Commission.
“Historically, cavernomas have been managed primarily with observation, surgical resection, and occasionally radiotherapy. However, for a number of reasons, many patients with cavernomas must endure a life with neurologic symptoms,” said Ryan Kellogg, MD, Investigator at the University of Virginia. “This group of patients has long needed a new modality of treatment, and the opening of the SYCAMORE study, the first industry-sponsored study in the field, is an important step toward potential treatment options to reduce or eliminate the burden of this neurological disease.”
A Phase II trial testing the safety and tolerability of the medicine in patients with CCM enrolled its first patient in March 2022. It is designed as a multi-center, randomized, double-blind, placebo-controlled study to investigate the safety, efficacy and pharmacokinetics of REC-994. The study is expected to enroll approximately 60 patients.
PROPRANOLOL
Propranolol is a beta-blocker that can be used to treat infantile hemangiomas. Several reports in the medical literature describe successful treatment of a giant infantile brain cavernoma, as well as two adult women with symptomatic and bleeding CCM lesions. Further studies are ongoing to investigate the biological effects of propranolol in CCM patients. A clinical trial to investigate the effects of propranolol treatment for CCM completed enrolling at multiple centers across Italy in late 2019. The trial will run for 2 years, through 2021.
BA-1049
BA-1049 is a specific Rho Kinase inhibitor developed by a pharmaceutical company, BioAxone Biosciences, and now licensed by Neurelis, a company that plans to take the medicine to human trials. Working in collaboration with researchers at Duke University and the University of Chicago, BA-1049 has been shown to reduce lesion volume and hemorrhage in mouse models.