FDA draft guidance aims to help sponsors develop drugs for radiation exposure

The US Food and Drug Administration (FDA) on 19 April issued draft guidance that encourages sponsors to have “early and ongoing” communication with the agency in developing drugs to prevent or treat acute radiation syndrome (ARS), in an effort to overcome some of the challenges in developing these drugs.
 
ARS applies to a variety of clinical indications resulting from high doses of exposure to radiation.  The Centers for Disease Control and Prevention (CDC) defines ARS as “an acute illness caused by irradiation of the entire body (or most of the body) by a high dose of penetrating radiation in a very short period of time (usually a matter of 45 minutes).”
 
The guidance is not intended for drugs treating the “downstream effect” of exposure such as sepsis and does not address delayed effects of acute radiation exposure, such as radiation-induced lung injury.
 
Treatments for ARS are approved under FDA’s Animal Rule, which is a pathway to approve a drug or biological product without human clinical trials in limited circumstances, when human clinical trials are not ethical or feasible.
 
FDA said that “developing products under the Animal Rule can be very challenging.  Establishing early and ongoing communication with the review division is critical for a successful outcome.”
 
These drugs may also be eligible for expedited review programs such as fast track and priority review or for orphan drug designation. They also may be eligible for an emergency use authorization (EUA) or under an expanded access mechanism, according to the draft guidance. 
 
As part of such early communication, the agency encourages sponsors to request pre-investigational new drug (IND) meetings. These meetings “are useful to prevent unnecessary studies, to increase the likelihood that needed studies will provide useful information, and to allow a discussion of scientific ideas and exchange of information and experience.”
 
At these meetings, the review division will work with sponsors to “clarify their best path forward, including the most appropriate animal models, primary endpoints for efficacy studies, and [pharmacodynamic] endpoints to support dose translation.”
 
FDA recommends that sponsors conduct a battery of studies to support drug approval. These include a preclinical evaluation of drug pharmacology (e.g., potency against target, selectivity) and toxicity, and natural history studies to characterize and select animal models that are intended to be translational or candidate models under the Animal Rule.
 
Sponsors also should conduct pharmacokinetic (PK) studies in relevant animal models and employ a range of drug doses to support the dosing regimen in humans.
 
Currently approved drugs for treating ARS -- filgrastim, pegfilgrastim, sargramostim, and romiplostim – were approved based on the results of a single animal efficacy study in a single non-human primate (NHP) model, since human challenge studies cannot be ethically conducted and field trials are not feasible, according to the draft guidance.
 
FDA is accepting comments on the draft guidance until 19 July 2023 at www.regulations.gov, Docket No. FDA-2023-D-1146.
 
Draft guidance, Federal Register Notice