Tekmira Pharmaceuticals’ Ebola drug may be used on infected patients
FDA modifies TKM-Ebola clinical hold to partial hold enabling use of investigational therapeutic
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VANCOUVER, British Columbia—Tekmira Pharmaceuticals Corporation, a leading developer of RNA interference (RNAi) therapeutics, today announced that the U.S. Food and Drug Administration (FDA) has verbally confirmed they have modified the full clinical hold placed on the TKM-Ebola Investigational New Drug Application (IND) to a partial clinical hold. This action enables the potential use of TKM-Ebola in individuals infected with Ebola virus during the current outbreak in West Africa that has resulted in more than 900 deaths.
"We are pleased that the FDA has considered the risk-reward of TKM-Ebola for infected patients. We have been closely watching the Ebola virus outbreak and its consequences, and we are willing to assist with any responsible use of TKM-Ebola. The foresight shown by the FDA removes one potential roadblock to doing so," said Dr. Mark Murray, CEO and president, Tekmira Pharmaceuticals. "This current outbreak underscores the critical need for effective therapeutic agents to treat the Ebola virus. We recognize the heightened urgency of this situation, and are carefully evaluating options for use of our investigational drug within accepted clinical and regulatory protocols."
TKM-Ebola, an anti-Ebola virus RNAi therapeutic, is being developed by Tekmira Pharmaceuticals under a $140 million contract with the U.S. Department of Defense's Medical Countermeasure Systems BioDefense Therapeutics (MCS-BDTX) Joint Product Management Office.
The company remains on clinical hold as it relates to the multi-ascending dose portion of the Phase 1 clinical study in healthy volunteers. "We are focused on an expedient resolution of this so that we can advance our TKM-Ebola to evaluate the multiple ascending dose regimen," said Murray.
The study is designed to assess the safety, tolerability and pharmacokinetics of administering TKM-Ebola to healthy adult volunteers without administering any steroid pre-medications. Earlier preclinical studies were published in the medical journal The Lancet and demonstrated that when siRNA targeting the Ebola virus and delivered by Tekmira's lipid nanoparticle (LNP) technology were used to treat previously infected non-human primates, the result was 100 percent protection from an otherwise lethal dose of Zaire Ebola virus (Geisbert et al., The Lancet, Vol 375, May 29, 2010). In March 2014, Tekmira was granted a Fast Track designation from the U.S. Food and Drug Administration for the development of TKM-Ebola.
The clinical hold letter confirms that the FDA is seeking data to elucidate the mechanism of potential cytokine release and a modification to the protocol for the multiple ascending dose portion of the trial to ensure the safety of healthy volunteers.
"It is important to highlight that the study protocol for the TKM-Ebola Phase 1 trial called for an interim review of the data from the single ascending dose portion of the trial before proceeding to the multiple ascending dose portion of the study. I wish to emphasize this trial is unique. It represents the first RNAi study involving the daily treatment of healthy volunteers, without steroid pre-medication or any other type of pre-medication, and with multiple ascending doses," said Murray. "Furthermore, the multiple ascending dose portion of the study, as originally proposed, reflects the intense dosing regimen that would be used in patients lethally infected with Ebola virus."
"It is important to highlight that the study protocol for the TKM-Ebola Phase 1 trial called for an interim review of the data from the single ascending dose portion of the trial before proceeding to the multiple ascending dose portion of the study. I wish to emphasize this trial is unique. It represents the first RNAi study involving the daily treatment of healthy volunteers, without steroid pre-medication or any other type of pre-medication, and with multiple ascending doses," said Murray. "Furthermore, the multiple ascending dose portion of the study, as originally proposed, reflects the intense dosing regimen that would be used in patients lethally infected with Ebola virus."
The company is assembling the data requested by the FDA and shares its commitment to patient safety. Murray added, "The mechanism for cytokine release is understood and we will be modifying our study protocol to further ensure subject safety. Our team is working expediently to respond to the FDA. We are mindful of the need for this important therapeutic in situations such as the ongoing Ebola outbreak in West Africa. However, TKM-Ebola is currently an unapproved agent and the regulatory framework to support its use in Africa has not been established at this time."
The U.S. Department of Defense Joint Project Manager Medical Countermeasure Systems (JPM-MCS) is a component of the Joint Program Executive Office for Chemical and Biological Defense, which aims to provide U.S. military forces and the nation with safe, effective and innovative medical solutions to counter chemical, biological, radiological and nuclear threats. JPM-MCS facilitates the advanced development and acquisition of medical countermeasures and systems to enhance biodefense response capability.
Tekmira Pharmaceuticals Corporation is a biopharmaceutical company focused on advancing novel RNAi therapeutics and providing its leading lipid nanoparticle (LNP) delivery technology to pharmaceutical partners. Tekmira has been working in the field of nucleic acid delivery for over a decade and has broad intellectual property covering LNPs. Tekmira is based in Vancouver, B.C., Canada.
