Researchers have demonstrated the potential of a new drug—ataciguat—to significantly slow the progress of aortic stenosis.
Results of the drug’s effectiveness have been shown in preclinical and clinical studies, published in Circulation, and the team behind the research are seeking to launch a pivotal trial to demonstrate the long-term safety and effectiveness of the treatment.
“This research represents a significant advancement in the treatment of aortic valve stenosis,” comments Jordan Miller, director of the Cardiovascular Disease and Aging Laboratory at Mayo Clinic (Rochester, USA), a co-author on the research paper. “Ataciguat has the potential to substantially delay or even prevent the need for valve replacement surgery, significantly improving the lives of millions.”
The research is part of a collaboration between Mayo Clinic, the National Institutes of Health (NIH), the University of Minnesota (Minneapolis, USA), and Sanofi Pharmaceuticals, conducted under an academic-industry partnership grant administered by the National Center for Accelerating Translational Sciences and a Minnesota Biotechnology and Genomics Partnership grant.
In their Circulation paper, the researchers write that they tested the hypothesis that reactivation of oxidised soluble guanylate cyclase (sGC), the primary receptor for nitric oxide, with ataciguat is a safe and effective strategy to slow the progression of fibrocalcific aortic valve stenosis.
The study team used quantitative real-time reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry to characterise sGC signalling and the biological effects of the drug on signalling cascades related to nitric oxide, calcification, and fibrosis in excised human aortic valve tissue, aortic valve interstitial cells, and mouse aortic valves.
They then conducted randomised placebo controlled phase I and II trials, showing 14-day safety and tolerance and six-month efficacy, respectively, in patients with moderate aortic valve stenosis. The phase II trial in 23 patients showed a 69.8% reduction in aortic valve calcification progression at six months compared to placebo, and patients receiving ataciguat tended to maintain better heart muscle function. Crucially, the research team confirmed that—despite its profound effect on slowing valve calcification—ataciguat did not negatively impact bone formation.
