Aortic valve stenosis (AVS) is a significant health issue affecting more than 1.5 million Americans and millions globally. Researchers at the Mayo Clinic are investigating the potential of a new drug called ataciguat to manage AVS. Results from preclinical and clinical studies, published in Circulation, indicate that ataciguat has promising potential to substantially slow disease progression.
The next critical step towards establishing the drug’s long-term effectiveness and safety is conducting a phase 3 trial. Efforts to launch this pivotal study are underway with an industry partner. In AVS, calcium deposits accumulate and narrow the aortic valve, forcing the heart to work harder to pump blood. The condition typically progresses over time, leading to symptoms such as chest pain, shortness of breath, and fatigue in individuals aged 65 or older.
The current standard of care—watchful waiting—is associated with reduced quality of life until the disease reaches a severe stage that necessitates surgical or interventional valve replacement. This research represents a significant advancement in AVS treatment. Ataciguat has potential to substantially delay or prevent the need for valve replacement surgery, thereby significantly improving millions’ lives.
Jordan Miller, Ph.D., Director of the Cardiovascular Disease and Aging Laboratory at Mayo Clinic, points out that the impact extends beyond simply delaying surgery. Younger patients with aggressive disease or congenital valve defects may develop symptoms in midlife. If a patient requires valve replacement before age 55, there is more than a 50% chance they will need multiple valve replacements over their lifetime due to implanted valve recalcification.
Ataciguat, which slowed the progression of native aortic valve calcification in clinical trials, offers potential for patients to reach at least age 65 without requiring further surgeries. The older a patient is, the less likely it is that an implanted valve will calcify again. Over the past decade, Mayo Clinic’s research has revealed that ataciguat reactivates a critical pathway in preventing valvular calcification and stenosis.
Preclinical studies in mice showed this drug substantially slowed disease progression even when treatment was initiated after the condition had developed. Clinical trials with patients having moderate AVS demonstrated that once-daily dosing of ataciguat was well-tolerated, accompanied by minimal side effects compared to placebo. This latest phase 2 trial involving 23 patients revealed a 69.8% reduction in aortic valve calcification progression at six months compared to the placebo group.
Patients receiving ataciguat also exhibited better heart muscle function. Crucially, researchers confirmed that despite its profound effect on slowing valve calcification, ataciguat did not negatively impact bone formation. This important finding is due to a collaborative effort involving Mayo Clinic, the National Institutes of Health, the University of Minnesota, and Sanofi Pharmaceuticals.
The research was conducted under an innovative academic-industry partnership grant administered by the National Center for Accelerating Translational Sciences and a Minnesota Biotechnology and Genomics Partnership grant. It’s important to note that Mayo Clinic and Dr. Miller have financial interests in the intellectual property referenced in this news release, but any revenue will be used to support their not-for-profit mission in patient care, education, and research.
