Aortic valve stenosis (AVS) is a serious health issue affecting over 1.5 million Americans and millions of others worldwide. Researchers at the Mayo Clinic are investigating a new drug called ataciguat to manage AVS. Findings from preclinical and clinical studies, published in Circulation, suggest that ataciguat has potential to significantly slow disease progression.
The final step to establish the drug’s long-term effectiveness and safety is a phase 3 trial. Efforts to launch this pivotal trial are underway with an industry partner. In AVS, calcium deposits build up and narrow the aortic valve, forcing the heart to work harder to move blood. The condition typically progresses over time, causing symptoms like chest pain, shortness of breath and fatigue in people over age 65.
The current standard of care – watchful waiting – often leads to reduced quality of life before the condition is severe enough for surgical or interventional valve replacement. This research represents a significant advancement in the treatment of aortic valve stenosis. Ataciguat has potential to substantially delay or even prevent need for valve replacement surgery, significantly improving lives of millions.
Dr Jordan Miller, Ph.D., Director of Cardiovascular Disease and Aging Laboratory at Mayo Clinic notes that impact extends beyond simply delaying surgery. Younger patients with aggressive disease or congenital valve defects may develop symptoms in midlife. If patient requires valve replacement before age 55, there is more than 50% likelihood they will require multiple valve replacement surgeries over lifetime due to recalcification of implanted valve.
Ataciguat, which slowed progression of native aortic valve calcification in clinical trial, offers potential for once-in-a-lifetime procedure if they can reach age 65. The older patient is, the less likely the implanted valve will calcify. Over past decade Mayo Clinic’s research revealed that ataciguat reactivates pathway crucial in preventing valvular calcification and stenosis.
Preclinical studies in mice showed that drug substantially slowed disease progression even when treatment began after disease was established. Clinical trials in patients with moderate AVS demonstrated that once-daily ataciguat dosing well tolerated, with minimal side effects compared to placebo. This latest phase 2 trial in 23 patients showed a 69.8% reduction in aortic valve calcification progression at six months compared to placebo.
Patient receiving ataciguat tended maintain better heart muscle function. Crucially research team confirmed that despite its profound effect on slowing valve calcification, did not negatively impact bone formation. This important finding is the result of collaborative effort between Mayo Clinic National Institutes of Health University of Minnesota and Sanofi Pharmaceuticals.
The research was conducted under innovative academic-industry partnership grant administered by National Center for Accelerating Translational Sciences and a Minnesota Biotechnology Genomics Partnership grant.
