New Drug for Aortic Valve Stenosis May Slow Disease Progression and Delay Surgery

Aortic valve stenosis (AVS) is a major health issue, impacting over 1.5 million Americans and millions more worldwide. Researchers at the Mayo Clinic are investigating a new drug, ataciguat, for treating AVS. Early preclinical and clinical study results, published in Circulation, suggest that ataciguat could effectively slow the progression of the disease. The next crucial step is a phase 3 trial to confirm its long-term safety and efficacy, which will soon begin in collaboration with an industry partner (1^✔ ✔Trusted Source
Reactivation of Oxidized Soluble Guanylate Cyclase as a Novel Treatment Strategy to Slow Progression of Calcific Aortic Valve Stenosis: Preclinical and Randomized Clinical Trials to Assess Safety and Efficacy

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Understanding Aortic Valve Stenosis

In AVS, calcium deposits accumulate on the aortic valve, narrowing it and making the heart work harder to pump blood. The condition worsens over time, with symptoms like chest pain, shortness of breath, and fatigue commonly affecting those over 65. The current approach, known as "watchful waiting," can reduce quality of life before the condition becomes severe enough to require surgery or a valve replacement intervention.

"This research marks a major breakthrough in treating aortic valve stenosis," says Jordan Miller, Ph.D., director of the Cardiovascular Disease and Aging Laboratory at Mayo Clinic. "Ataciguat could greatly delay or even eliminate the need for valve replacement surgery, offering significant improvements to the lives of millions."

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How Ataciguat Could Offer a Single Procedure Option

Dr. Miller highlights that the benefits go beyond just delaying surgery. Younger patients with aggressive AVS or congenital valve defects may experience symptoms in midlife. If they need valve replacement before 55, there's over a 50% chance they'll require multiple surgeries due to recalcification of the implanted valve. However, ataciguat, which slowed the progression of native valve calcification in clinical trials, could offer the chance for a single procedure if patients reach 65, as the likelihood of valve calcification decreases with age.

Over the past decade, Mayo Clinic's research discovered that ataciguat reactivates a key pathway that helps prevent valvular calcification and stenosis. Preclinical studies in mice showed that the drug significantly slowed disease progression, even when treatment started after the disease had already developed.

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Ataciguat Well Tolerated in Clinical Trials

Clinical trials in patients with moderate AVS showed that once-daily dosing of ataciguat was well tolerated, with few side effects compared to a placebo. In the latest phase 2 trial involving 23 patients, ataciguat resulted in a 69.8% reduction in aortic valve calcification progression after six months, and patients on the drug also tended to maintain better heart muscle function. Importantly, the research team confirmed that, despite its strong impact on slowing valve calcification, ataciguat did not negatively affect bone formation.

This key finding comes from a collaborative effort between Mayo Clinic, the National Institutes of Health, the University of Minnesota, and Sanofi Pharmaceuticals. The research was supported by an innovative academic-industry partnership grant from the National Center for Accelerating Translational Sciences, as well as a Minnesota Biotechnology and Genomics Partnership grant.

Reference:

1. Reactivation of Oxidized Soluble Guanylate Cyclase as a Novel Treatment Strategy to Slow Progression of Calcific Aortic Valve Stenosis: Preclinical and Randomized Clinical Trials to Assess Safety and Efficacy - (https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.066523)

Source-Eurekalert