Tekmira Pharmaceuticals Corporation, a biopharmaceutical company focused on advancing novel RNAi therapeutics and providing its leading lipid nanoparticle delivery technology to pharmaceutical partners, has started patient enrollment in its phase 1 clinical trial for TKM-Ebola.
"The initiation of TKM-Ebola clinical development marks another important milestone for Tekmira. TKM-Ebola continues to be developed under a $140 million contract with the US Government's Transformational Medical Technologies (TMT) Programme, which allows us to advance this programme to FDA approval as well as develop further innovations to Tekmira's broader LNP technology platform," said Dr Mark J Murray, Tekmira's president and CEO.
The phase 1 TKM-Ebola clinical trial is a placebo-controlled, single-blind, single-ascending dose study with additional multiple-ascending dose cohorts in healthy human volunteers. The objective of the Phase 1 trial is to assess the safety and tolerability of TKM-Ebola and evaluate the pharmacokinetics and systemic exposure following both a single-ascending dose (SAD) and multiple-ascending doses (MAD) of TKM-Ebola. A maximum of 56 healthy adult subjects will participate in this study, in two stages. In stage one, the SAD phase will have up to six cohorts with four subjects (three receiving TKM-Ebola and one receiving placebo) in each cohort. In stage two, the MAD portion of the study will have up to three cohorts with four subjects per cohort (three receiving TKM-Ebola and one receiving placebo) in each cohort.
TKM-Ebola will be developed under specific FDA regulatory guidelines (called the "Animal Rule"), which are designed to advance therapeutics that cannot meet the requirements for traditional approval because human efficacy studies are not feasible.
In addition to the TKM-Ebola product development collaboration, the TMT program has supported further development of Tekmira's LNP technology, resulting in a successful 100-fold scale up of the LNP manufacturing process as well as the development of a lyophilization (freeze drying) process while maintaining key LNP product characteristics. These advances will support the late stage clinical development and commercialization of TKM-Ebola as well as other LNP-enabled products.
Tekmira believes its LNP technology represents the most widely adopted delivery technology for the systemic delivery of RNAi therapeutics. Tekmira's LNP platform is being utilized in multiple clinical trials by both Tekmira and its partners.
Tekmira is developing TKM-Ebola, a systemically delivered RNAi therapeutic that utilizes Tekmira's lipid nanoparticle (LNP) delivery technology, for the treatment of Ebola virus infection. There are no approved treatments for Ebola or other haemorrhagic fever viruses. Preclinical studies published in the medical journal The Lancet demonstrated that when small interfering RNA (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 per cent protection from an otherwise lethal dose of Zaire Ebola virus (Geisbert et al., The Lancet, Vol 375, May 29, 2010).
RNAi therapeutics have the potential to treat a broad 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 therapeutics, such as "siRNAs," require delivery technology to be effective systemically. Tekmira believes its LNP technology represents the most widely adopted delivery technology for the systemic delivery of RNAi therapeutics. Tekmira's LNP platform is being utilized in multiple clinical trials by both Tekmira and its partners. Tekmira's LNP technology (formerly referred to as stable nucleic acid-lipid particles or SNALP) encapsulates siRNAs with high efficiency in uniform lipid nanoparticles that are effective in delivering RNAi therapeutics to disease sites in numerous preclinical models. Tekmira's LNP formulations are manufactured by a proprietary method which is robust, scalable and highly reproducible and LNP-based products have been reviewed by multiple FDA divisions for use in clinical trials. LNP formulations comprise several lipid components that can be adjusted to suit the specific application.