AesRx, a biopharmaceutical company dedicated to the development of treatments for two orphan diseases, will present data from the recently completed phase 1 study of its anti-sickling agent Aes-103 at the 2012 American Society of Hematology (ASH) meeting in Atlanta. The data will be presented in a poster session on December 10.

Data shows the drug is safe and well-tolerated. It also shows Aes-103 is biologically active in humans in a manner consistent with its proposed mechanism of action in sickle cell disease.

The first-in-human, double-blind, placebo-controlled clinical trial was conducted in collaboration with the National Institutes of Health (NIH). The trial examined the effects of single doses of Aes-103 at 300 mg, 1000 mg, 2000 mg and 4000 mg or placebo in 20 healthy normal volunteers of African-American descent. Endpoints were focused on safety, pharmacokinetics and pharmacodynamic changes.

The safety measures showed no clinically significant adverse effects on vital signs, ECGs, clinical laboratory tests, physical exams or adverse events. All adverse events were mild and transient. The pharmacokinetics of Aes-103 showed 5-10 fold higher drug concentrations in red blood cells, which is the site of action of Aes-103 on haemoglobin, compared to drug concentrations in plasma. Aes-103 was rapidly absorbed and the amount of Aes-103 in plasma and red blood cells was largely dose proportional.

Pharmacodynamic effects were also examined to determine the ability of Aes-103 to increase the oxygen affinity of the haemoglobin of the healthy volunteers. In a hypoxia challenge test, the subjects inhaled low levels of oxygen (12%) while their blood oxygen levels (SpO2%) were monitored. Aes-103 in 1000-4000 mg doses reduced the hypoxia-related drop in subjects’ SpO2% compared to placebo and the 300 mg dose.

“We are very pleased with the results of our Phase 1 study,” commented Stephen R. Seiler, AesRx’s Chief Executive Officer. “In sickle cell patients, increasing the oxygen affinity of haemoglobin is known to prevent red blood cell sickling. The ability of Aes-103 to provide protection in a hypoxia challenge of healthy volunteers indicates biological activity in humans in a manner consistent with Aes-103’s proposed mechanism of action in sickle cell disease.”

Based on these positive results, a second trial of similar design enrolling patients with sickle cell disease has been initiated at the NIH Clinical Center in Bethesda, Maryland.

The reported phase 1 study and the ongoing phase 1/2a study in sickle cell patients are part of a multi-institute, public-private translational research collaboration involving AesRx and two separate NIH components—the National Heart, Lung, and Blood Institute (NHLBI) and the National Center for Advancing Translational Sciences (NCATS) through its Therapeutics for Rare and Neglected Diseases (TRND) programme.