The US Food and Drug Administration (FDA) has reportedly partially lifted a clinical hold that it had placed last month on one of the only investigational Ebola treatments that has been tested in humans thus far.
The drug, an RNA interference product known as TKM-Ebola, is manufactured by Tekmira Pharmaceuticals.
In a statement on 7 August 2014, Tekmira said that FDA had "verbally confirmed" that it had modified its clinical hold on the drug. The hold was initiated in early July 2014 after the company reported that one of its patients enrolled in a Phase I clinical trial had experienced a potentially deadly side effect, cytokine release, at elevated doses of the drug.
The agency reportedly placed the study on hold while it asked Tekmira to compile more data about the mechanism of cytokine release.
Regulation of Clinical Holds
As reported yesterday by Regulatory Focus, FDA had indicated that it might be willing to lift the hold in light of a massive outbreak of the Ebola virus in Western Africa, which has already killed hundreds of patients.
Under 21 CFR 312.42, clinical holds—orders to stop a clinical trial—are ordered by FDA when a clinical investigation reveals information that indicates an "unreasonable and significant risk of illness or injury."
But under federal regulations (21 CFR 312.42(e)), FDA can lift—either completely or partially—the clinical hold if the agency is satisfied that the investigation can proceed.
"A future proposal for a study or emergency use in a different population, for example in patients with disease, might have an acceptable risk-benefit balance," FDA explained to Focus in a statement. "If there is a reasonable prospect that the benefits of investigational use may outweigh the risks for a specific population, we may consider permitting that study to proceed."
The hold could also be lifted based on the "context for use for the product and the patient population being studied."
For more on the regulation of Ebola therapies, please read our extensive Regulatory Explainer on the topic.
And it's exactly that "context for use" that seems to be driving FDA's decision to partially lift the clinical hold on TKM-Ebola. While the original hold will remain in effect, FDA will allow for its use in patients infected with Ebola.
That could put Tekmira into a unique position, as one of the only Ebola treatments to be used thus far, Mapp Biopharmaceuticals' ZMapp, is in scarce supply. Tekmira, having already scaled up its production processes to allow for Phase I human trials, may be able to supply more of the drug—a key benefit to patients, assuming the drug works as intended.
The company said it is "willing to assist with any responsible use of TKM-Ebola," and that FDA's actions remove a "potential roadblock for doing so."
FDA's clinical hold is still in effect for healthy patients not infected with Ebola, the company said.