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 58th
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.
Onconova Therapeutics, Inc.