Phase 2 trial of tiprelestat for PAH receives FDA advice
'Tiprelestat holds the promise of a disease-modifying therapy': Researcher
The U.S. Food and Drug Administration (FDA) has provided Tiakis Biotech with advice for a planned Phase 2 clinical trial testing tiprelestat for pulmonary arterial hypertension (PAH).
The ATHENA trial, which will assess the treatment’s safety and efficacy, is expected to enroll 90 patients, randomly assigned to receive tiprelestat or a placebo, in combination with standard of care. Tiakis states the FDA supports the study’s design and its primary and secondary outcome measures.
“Given its unique mechanism of action addressing major pathological [disease-related] processes in PAH, specifically inflammation and BMPR2 deficiency, tiprelestat holds the promise of a disease-modifying therapy for PAH. Data from the planned 4-week withdrawal period are expected to confirm this hypothesis,” Roham Zamanian, MD, professor of medicine at Stanford University and principal investigator of the ATHENA trial, said in a company press release.
PAH is caused by the narrowing of pulmonary arteries, the blood vessels that carry blood through the lungs. This restricts blood flow in the lungs and leads to high blood pressure, or hypertension.
The disease can be caused by mutations, with the BMPR2 gene being particularly relevant. This gene codes for a protein that regulates the growth of blood vessel cells in the lungs. Such mutations have been associated with the overgrowth of smooth muscle cells in pulmonary vessels, which contributes to vascular remodeling that underlies the narrowing of blood vessels.
Tiprelestat is lab-made version of anti-inflammatory protein called elafin
Tiprelestat is a lab-made version of elafin, an anti-inflammatory protein that works by blocking the activity of neutrophil elastase and proteinase 3, two proteins involved in inflammation. Elafin deficiency and high levels of elastase have been identified in PAH patients.
In five placebo-controlled trials, the treatment demonstrated a good safety profile, the company states on its website.
In animal models, tiprelestat reduced vascular remodeling, according to the company. In preparation for the future trial, a six-month toxicology study in rats is currently being conducted.
ATHENA’s main goal is to assess changes in pulmonary vascular resistance, or the resistance of pulmonary arteries against blood flow. Secondary measures include the six-minute walk distance, or the distance walked in six minutes, as a measure of functional status.
The trial also includes a four-week period in which patients are withdrawn from the active therapy to study whether tiprelestat has disease-modifying potential.
The therapy has been granted orphan designation in the U.S. and in Europe for PAH. The designation is meant to accelerate the development of treatments for rare conditions and provides certain benefits, including tax credits and a period of market exclusivity if the therapy is ultimately approved.
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