The randomized, double-blind and placebo-controlled trial evaluated the safety, tolerability and pharmacokinetics of 0.03 mg, 0.05 mg, 0.1 mg and 0.2 mg single doses of APD811. The trial evaluated 32 healthy volunteers in four cohorts of eight participants each — six randomized to APD811 and two to placebo. APD811 was rapidly absorbed and demonstrated dose-proportional pharmacokinetic exposure over the tested dose range. The terminal half-life was approximately 20 hours.
The most frequent treatment-emergent adverse events were headache, vomiting, nausea, jaw pain and flushing. Dose-limiting adverse events of nausea and vomiting occurred at the 0.2 mg dose. As compared to placebo, heart rate trended higher at the 0.05 mg, 0.1 mg and 0.2 mg doses and the corrected QT (QTc) interval trended higher at the 0.1 mg and 0.2 mg doses. Arena believes the QTc observation is not supported by preclinical data and will further evaluate this in future studies. No serious adverse events were reported.
"We are encouraged by the results of this early stage clinical trial that suggest APD811 has the potential for once-daily, oral dosing, and our next step will be to evaluate the safety, tolerability and pharmacokinetics of multiple dosing and the optimal titration schedule in a Phase 1b trial," said
About Pulmonary Arterial Hypertension (PAH)
PAH is a progressive, life-threatening disorder characterized by increased pressure in the arteries that carry blood from the heart to the lungs. The increased pressure strains the heart, which can lead to limited physical activity and a reduced life expectancy. Over time, the heart weakens, can no longer pump blood efficiently and may eventually fail.
APD811, an orally bioavailable agonist of the prostacyclin receptor, is an investigational drug candidate discovered by Arena and intended for the treatment of PAH. Prostacyclin receptor agonists slow disease progression and improve exercise tolerance in PAH patients and are among the treatments administered as standard of care for advanced PAH. Currently available prostacyclin receptor agonists belong to the prostanoid class of molecules, and these products need to be administered frequently or continuously through intravenous, subcutaneous or inhaled delivery methods. Arena believes that an orally bioavailable, non-prostanoid prostacyclin receptor agonist that provides clinical benefits similar to currently available prostacyclin receptor agonists has the potential to improve the standard of care for PAH.
Arena is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing oral drugs that target G protein-coupled receptors, an important class of validated drug targets, in four major therapeutic areas: cardiovascular, central nervous system, inflammatory and metabolic diseases. Arena's most advanced drug candidate is intended for weight management.
Arena Pharmaceuticals® and Arena® are registered service marks of the company.
Certain statements in this press release are forward-looking statements that involve a number of risks and uncertainties. Such forward-looking statements include statements about the advancement, therapeutic indication and use, safety, efficacy, tolerability and mechanism of action of APD811; the potential of APD811 and orally bioavailable, non-prostanoid prostacyclin receptor agonists in general; future study and evaluation of APD811; Arena's commitment to advance its pipeline; the therapeutic indication of Arena's most advanced drug candidate; and Arena's beliefs, focus, goals, strategy, research and development programs, and ability to develop compounds and commercialize drugs. For such statements, Arena claims the protection of the Private Securities Litigation Reform Act of 1995. Actual events or results may differ materially from Arena's expectations. Factors that could cause
actual results to differ materially from the forward-looking statements include, but are not limited to, the following: there was a small safety margin from the no observed adverse effect level to significant adverse events in preclinical studies of APD811, and APD811 could have an unacceptable safety and efficacy profile in humans; the timing of regulatory review and approval is uncertain; the risk that data and other information related to Arena's research and development programs may not meet safety or efficacy requirements or otherwise be sufficient for regulatory approval; Arena's response to the CRL for the lorcaserin NDA or submission of a Marketing Authorization Application for regulatory approval of lorcaserin may not be submitted when anticipated, if at all; the
Contact: Arena Pharmaceuticals, Inc.
Media Contact: Russo Partners
David Schull, President
President and CEO
Manager, IR and Corporate Communications
Anthony J. Russo, Ph.D., CEO
858.453.7200, ext. 1479
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