The US Food and Drug Administration (FDA) issued draft guidance Monday to describe a “streamlined nonclinical program” aimed at aiding sponsors with the development of drugs used for treating severely debilitating or life-threatening hematologic disorders (SDLTHDs).
As defined under current regulations, examples of SDLTHDs—conditions, other than cancer, “in which life expectancy is short or quality of life is greatly diminished despite available therapies”—include hemophagocytic lymphohistiocytosis, cold agglutinin and severe aplastic anemia, among others, FDA said. Draft guidance
from August 2015 on rare disease drug development is not specific to SDLTHDs.
Radiopharmaceuticals, vaccines, cellular and gene therapy products, as well as blood products fall outside of the guidance’s scope, and it largely points to recommendations in guidelines previously developed via the International Council for Harmonisation (ICH) for those product types.
Sponsors should use ICH’s S9 from 2010 on nonclinical evaluations of anticancer pharmaceuticals, including combination therapies, as a reference for additional information on this topic.
The new 7-page draft guidance
separates nonclinical evaluation studies for SDLTHDs into nine categories—pharmacology, safety pharmacology, general toxicology, genotoxicity, reproductive toxicology, carcinogenicity, immunotoxicity, photosafety testing and pharmacokinetics.
It also provides timing recommendations for submissions to FDA of nonclinical study results.
“The sponsor can provide study results earlier than the timings listed, and is encouraged to do so, when a cause of concern exists,” the agency clarified. “For example, results of secondary pharmacology studies may be provided when phase 1 clinical data indicate unexpected severe toxicities.”
In general, toxicology studies for safety investigations of combined pharmaceuticals intended for treatment of SDLTHDs and juvenile animal studies
for SDLTHDs are not warranted for FDA purposes.
In 2016, officials from FDA's Office of Hematology and Oncology Products at the Center for Drug Evaluation and Research, reached the conclusion in retrospective analysis
that “juvenile animal studies conducted to date have not provided useful information to support [first-in-pediatric] development for anticancer drugs, consistent with the recommendations outlined in ICH S9."
Severely Debilitating or Life-Threatening Hematologic Disorders: Nonclinical Development of Pharmaceuticals Guidance for Industry