Karos Pharmaceuticals recently announced it has advanced its small molecule investigational drug candidate, KAR5585, into the clinic for the treatment of pulmonary arterial hypertension (PAH) and other rare conditions marked by extensive fibrosis.
KAR5585 selectively inhibits tryptophan hydroxylase 1 (TPH1), and was developed to reduce peripheral serotonin (5-HT) and 5-HT-associated fibrosis and vascular remodeling, the hallmarks of PAH.
The company has completed the single ascending dose part of the Phase 1 trial assessing KAR5585 in 120 healthy volunteers, and is currently running the multiple ascending dose part of the clinical trial. Karos expects to report data from the Phase 1 clinical program in the second half of this year.
The biomarkers included in the multiple-dose part of the trial are anticipated to provide insight into the mechanism of action of KAR5585, and the dose-range required to reduce peripheral 5-HT. Upon this advancement, Karos expects to initiate a Phase 2 clinical trial on KAR5585 as a once-a-day therapy in patients with PAH.
“PAH is a uniformly fatal disease if left untreated, and while there are current treatments available, they do not halt or reverse the primary pathophysiology underlying disease progression,” said Lewis J. Rubin, M.D., emeritus director of pulmonary and critical care and professor of medicine at the University of California, San Diego School of Medicine, in a press release.
“Critically important will be to develop new treatments that can alter the course of disease and deliver improvements in patient survival and quality of life. Based on the early evidence to date, I believe that peripheral serotonin modulation holds great potential, and I look forward to the further advancement of Karos’ program,” Rubin said.
“Karos is dedicated to discovering and developing novel therapies that address the role of dysregulated peripheral serotonin seen in diseases associated with tissue fibrosis and inflammation,” said Peter U. Feig, M.D., chief medical officer at Karos. “With PAH as our lead disease target, we are also advancing programs in pulmonary fibrosis unrelated to PAH, other diseases associated with fibrosis, and carcinoid syndrome. Our goal is to have proof-of-concept studies in two or more indications in 2017.”
PAH is an increase of blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature. The early symptoms of PAH, such as dyspnea, dizziness, and fatigue, are often mild and are common to many other conditions. At rest, there are often no symptoms and no apparent signs of illness. As a result, time from symptom onset to disease diagnosis is, on average, more than two years. This means that PAH is frequently not recognized until the disease is relatively advanced.
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