Positive data from three Onconova Ex-RAD clinical trials on acute radiation syndrome

Onconova Therapeutics, Inc.Oct 4 2012

Onconova Therapeutics, Inc. today announced positive human safety, tolerability, and pharmacokinetic data from three clinical trials of Ex-RAD (recilisib sodium, ON 01210.Na), a novel radioprotectant being developed as a medical countermeasure for the treatment of acute radiation syndrome (ARS). Ex-RAD and other radioprotection strategies are increasingly important as the threat of accidental and intentional exposure to harmful radiation is becoming a major security concern. These new data were presented on October 3, 2012 at the 58^th Annual Radiation Research Society Meeting in San Juan, Puerto Rico.    

"The collaborative Ex-RAD program is advancing towards the final stages of development," said Manoj Maniar, Ph.D., Senior VP of Product Development for Onconova. "The data from these human safety trials are encouraging and support continued development of this novel radiation protector for potential prophylactic and therapeutic indications."

Dr. Amanda Gillum, Executive Director, Project Management, presented results from two Phase I clinical trials of subcutaneous (SC) Ex-RAD in healthy adult volunteers in a poster presentation entitled "Human safety testing of subcutaneously-administered Ex-RAD^® (ON 01210.Na), a small molecule radioprotection agent."

Subcutaneous (SC) Ex-RAD was studied in two randomized, placebo-controlled Phase I trials in healthy volunteers. In the first trial, 32 volunteers received doses of Ex-RAD ranging from 50 to 300 mg. The second trial, in which 20 volunteers were treated, examined the absorption of drug from various SC sites using a fractionated 2-dose regimen (200 & 400 mg total doses). In both trials, Ex-RAD was rapidly absorbed and found to be well-tolerated, without clinically significant drug-related systemic toxicity. Main adverse events were mild, self-limited injection site reactions, generally subsiding in a few hours. No clinically-significant trends were noted in inflammatory cytokines. High plasma levels of Ex-RAD, proportional to the full dose range, were rapidly achieved following the SC administrations. In the second study, absorption and the total drug exposure was similar, independent of the site of administration.

In a second poster, Dr. Chen Ren, Senior Research Scientist, presented the results from the first Phase I clinical trial of orally-administered Ex-RAD in a presentation entitled "Safety, tolerability and pharmacokinetic behavior of escalating single oral doses of Ex-RAD^® (ON 01210.Na) in healthy volunteers."

In this open-label, single-ascending dose study, three cohorts (3 healthy volunteers/cohort) received 200 to 800 mg oral Ex-RAD solution under fasting conditions. Ex-RAD was rapidly absorbed, well tolerated, and no drug-related systemic side-effects were observed. Ex-RAD displayed excellent oral bioavailability and pharmacodynamically relevant levels were readily achieved, suggesting that oral delivery of Ex-RAD is feasible. Furthermore, drug exposure achieved using the oral administration was ~135% of that observed with a 200-mg SC injection in an earlier clinical study, suggesting that the oral formulation has a higher relative bioavailability. Importantly, this oral formulation would provide a convenient route of administration for first-responders, civilian mass casualties, or at-risk populations who may face exposure to harmful ionizing radiation.