FDA modifies partial clinical hold on Tekmira's TKM-Ebola IND
The FDA has notified Tekmira Pharmaceuticals, a therapeutic solutions company focused on developing a cure for chronic hepatitis B virus infection (HBV) headquartered in Vancouver, BC, Canada, that the partial clinical hold on the company's Investigational New Drug application (IND) for TKM-Ebola has been modified to permit repeat dosing of healthy volunteers at a dose of 0.24mg/kg/day. The IND remains on partial clinical hold with regard to doses above 0.24mg/kg/day in healthy volunteers.
Tekmira plans to resume the TKM-Ebola phase I clinical trial in the coming weeks. The study is a randomized, single-blind, placebo-controlled study involving repeat dosing of a single cohort of healthy volunteers. Each subject will receive daily doses of 0.24mg/kg of TKM-Ebola or placebo for up to seven days. TKM-Ebola will be administered without steroid pre-medication. Results from the study are expected in the second half of 2015.
In July 2014, the company received notice from the FDA placing the TKM-Ebola IND on clinical hold until additional information was provided and the multiple ascending dose portion of the trial protocol was modified to ensure the safety of healthy volunteers. The clinical hold was subsequently modified in August to a partial clinical hold to permit the administration of TKM-Ebola to patients with a suspected or confirmed Ebola virus infection.
TKM-Ebola, an anti-Ebola virus RNAi therapeutic, is being developed under a $140 million contract with the U.S. Department of Defense's Medical Countermeasure Systems BioDefense Therapeutics (JPM-MCS-BDTX) Joint Product Management Office. 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 LNP technology were used to treat previously infected non-human primates, the result was 100% 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 FDA for the development of TKM-Ebola.
RNAi therapeutics have the potential to treat a number of human diseases by "silencing" disease causing genes. The discoverers of RNAi, a gene silencing mechanism used by all cells, were awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi trigger molecules often require delivery technology to be effective as therapeutics. Tekmira believes its LNP technology represents the most advanced and widely adopted delivery technology for the systemic delivery of RNAi triggers. Tekmira's LNP platform is being utilized in multiple clinical trials in various disease areas by Tekmira and its partners. Tekmira's LNP technology (formerly referred to as stable nucleic acid-lipid particles or SNALP) encapsulates RNAi triggers with high efficiency in uniform lipid nanoparticles that are effective in delivering these therapeutic compounds to disease sites.