New drug atakiguat shows promise for treating aortic valve stenosis

New drug atakiguat shows promise for treating aortic valve stenosis

Aortic valve stenosis (AVS) is a significant health problem that affects over 1.5 million Americans and millions more worldwide. Mayo Clinic researchers are studying the use of a new drug called ataciguat to manage AVs. Results from preclinical and clinical studies published inTrafficshow that ataciguat has the potential to significantly slow disease progression. The final step to determine the drug's long-term effectiveness and safety is a Phase 3 trial, and efforts to initiate this pivotal trial will soon take place 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 disease typically progresses over time with symptoms such as chest pain, shortness of breath and fatigue affecting people over 65 years of age. The current standard of care – watchful waiting – often results in a reduced quality of life before the condition is severe enough for the patient to seek surgical or interventional intervention.

This research represents a significant advance in the treatment of aortic valve stenosis. Ataciguat has the potential to significantly delay or even prevent the need for valve replacement surgery and improve the lives of millions. “

Jordan Miller, Ph.D., Director of Cardiovascular Disease and Aging, Mayo Clinic

Dr. Miller notes 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 a greater than 50% chance that they will require multiple valve replacement surgeries over their lifetime due to recalculation of the implanted valve. Ataciguat, which slowed the progression of native aortic valve calcification in the clinical trial, offers the potential for a one-time procedure if he can reach age 65. The older a patient is, the less likely the implanted valve is to calcify.

Over the past decade, Mayo Clinic research has found that ataciguat reactivates a pathway critical to preventing valve calcification and stenosis. Preclinical studies in mice showed that this drug essentially slowed the progression of the disease, even at the start of treatment after the disease had been established.

Clinical trials in patients with moderate AVs demonstrated that once-daily dosing of ataziguate was well tolerated with minimal side effects compared to placebo. This final phase 2 study in 23 patients showed a reduction in progression of aortic valve calcification at six months compared to placebo, and patients who received ataziguat tended to maintain better myocardial function. Crucially, the research team confirmed that ataciguat had no negative impact on bone formation, despite its profound effect on slowing valve calcification.

This important finding is the result of a collaboration between the Mayo Clinic, the National Institutes of Health, the University of Minnesota, and Sanofi Pharmaceuticals. The research was conducted under an academic research grant administered by the National Center for Accelerated Translational Sciences and the Minnesota Biotechnology and Genomics Partnership.

The Mayo Clinic and Dr. Miller has a financial interest in the intellectual property referenced in this press release. Mayo Clinic will use all revenue it receives to support its nonprofit mission of patient care, education and research.

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