Selexys Pharmaceuticals Corporation, a privately held biopharmaceutical company that is developing therapies to treat inflammatory and thrombotic diseases, has started enrolling patients in SUSTAIN, a phase II, multi-centre, randomized, placebo-controlled, double-blind, 12-month study to assess safety and efficacy of the anti-P-selectin monoclonal antibody SelG1 with or without hydroxyurea therapy in sickle cell disease patients with sickle cell-related pain crises.
The SUSTAIN trial will randomize approximately 174 patients to receive high dose SelG1, low dose SelG1 or placebo in the presence or absence of hydroxyurea therapy, the current standard of treatment. The study will examine the effectiveness of SelG1 in reducing the rate of sickle cell-related pain crises in each active dose level as compared to placebo. The study will be conducted in approximately 60 centres throughout the US.
“With the limited therapies available to patients with sickle cell disease, this trial with a novel P-selectin inhibitor is particularly exciting. Not only does it have the potential to improve the clinical outcomes in patients, its effects may be additive or synergistic with those of hydroxyurea, the only drug currently approved by the FDA for treatment of complications due to sickle cell disease,” stated Dr Kenneth Ataga, lead investigator and associate professor of Medicine in the Division of Hematology/Oncology, University of North Carolina at Chapel Hill.
“Data from preclinical sickle cell disease models suggest that blockade of P-selectin effectively prevents the painful stoppage of circulation in small blood vessels called vasoocclusion and maintains patent blood flow,” stated Dr Russell Rother, Selexys executive vice-president and chief operating officer. “In addition, results from our recently completed phase I study indicate that SelG1 is well tolerated in healthy human subjects. We now look forward to investigating its safety and efficacy in the sickle cell disease patient population."
SelG1 prevents certain blood cells from binding to one another and to the blood vessel walls. By stopping these cell-cell interactions, SelG1 may prevent small blood vessels from becoming blocked and reduce the occurrence and severity of pain crises as well as downstream complications such as stroke, heart attack and organ failure in sickle cell patients.
"We are excited to initiate our second clinical study with SelG1 and to test its potential benefit in the sickle cell patient population," said Dr Scott Rollins, president and CEO of Selexys. "The SUSTAIN study focuses on the ability of our novel anti-P-selectin antibody to reduce or prevent the occurrence of pain crises and thereby improve the lives of patients with sickle cell, a disease that largely affects African-Americans in the US.”
SelG1 is an investigational humanized monoclonal antibody directed against P-selectin, a key member of the adhesion molecule family known as the selectins. In preclinical studies, inhibition of P-selectin has been shown to effectively prevent vasoocclusion by blocking critical cell-cell interactions that drive this process. Therapeutic blockade of P-selectin may therefore reduce or prevent vasoocclusive crises in patients with sickle cell disease. The SelG1 programme for sickle cell disease is supported by Small Business Innovation Research (SBIR) fast-track award #5R44HL093893-02 and #2R44HL093893-03 through the National Heart, Lung and Blood Institute.