Cerenis to Present Clinical Proof-of-Concept Results
Cerenis Therapeutics SA, a biotech startup based in Toulouse, France with laboratory operations in Ann Arbor, said Monday it will present the results of two clinical proof-of-concept studies for its CER-627 program (niacin/aspirin combinations) at the 78th European Atherosclerosis Society Congress on June 20-23 in Hamburg, Germany.
Niacin has proven cardiovascular benefit, including reduction in morbidity and mortality. However, its usage has been limited by facial flushing. This side effect often prevents patients from titrating to adequate dose levels and frequently results in discontinuation of dosing altogether. Current niacin prescribing recommendations advise taking aspirin 30 minutes prior to niacin in order to inhibit COX1-dependent prostaglandin production in the skin, which is responsible for niacin-induced flushing. However, because aspirin is rapidly metabolized and removed from the circulation, its effectiveness is limited. Better anti-flushing effects may be achieved by controlling and coordinating aspirin and niacin exposure such that aspirin is present at sufficient levels in the skin prior to, and during niacin exposure.
Two Phase 1 proof-of-concept studies were conducted to evaluate simulated sustained-release aspirin regimens to decrease niacin-induced flushing. In the first study, 4 days of pre-dosing with 240 mg of aspirin, followed by a simulated sustained-release aspirin treatment regimen (20 mg/hr for 12 hrs), given in conjunction with 500 mg of immediate-release niacin at hour 6, was assessed in 30 subjects for its ability to inhibit niacin-induced flushing. The aspirin regimen resulted in a highly significant 53 percent reduction in the maximal severity of flushing compared with placebo. In the second study, flushing induced by a single two-gram dose of extended release-niacin was evaluated with two different sustained-release aspirin dosing regimens in 54 subjects. Regimen A consisted of 3 days of pre-dosing with 240 mg of aspirin, followed by aspirin 30 mg/kg for 8 hrs with extended-release niacin administered at hour 4. Regimen B consisted of no aspirin pre-dosing and aspirin 10 mg/hr for 6 hrs with extended-release niacin administered at hour 6. Regimen A significantly reduced the flushing by 37 percent compared with placebo where regimen B had no significant effect. It was concluded that the timing and duration of aspirin exposure relative to niacin is important in inhibiting niacin-induced flushing.
These data support the development of a fixed-dose combination product of sustained-release aspirin and delayed and extended-release niacin. Such a product would be expected to increase patient compliance thereby allowing niacin to attain its full potential for cardiovascular protection.
The goal of the CER-627 program is to develop a fixed dose combination of niacin and aspirin to treat dyslipidemia with low HDL, where the aspirin dosing is delivered by sustained release several hours in advance of niacin dosing. This dosing combination has an unexpectedly large ability to reduce flushing, and is supported by a portfolio of issued and pending patents. CER-627 is under phase 2 clinical development, with a focus on formulation optimization.
Cerenis Therapeutics is a multinational biopharmaceutical company dedicated to the discovery and development of novel HDL therapies for the treatment of cardiovascular and metabolic diseases. HDL is the primary facilitator of the reverse lipid transport, or RLT, pathway by which excess cholesterol is removed from arteries and is transported to the liver for elimination from the body. Cerenis is developing a portfolio of HDL therapies, including HDL mimetics for the rapid regression of atherosclerotic plaque in high-risk patients, and HDL elevators for patients with low HDL. Cerenis is well positioned to become the leader in the HDL therapeutic market with a broad portfolio of programs in development.
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