Tekmira Pharmaceuticals Completes ApoB SNALP Phase 1 Clinical Trial
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Tekmira Pharmaceuticals Corporation announced that it has concluded its ApoB SNALP Phase 1 human clinical trial. ApoB SNALP is designed to reduce the production of apolipoprotein B (ApoB), a protein produced in the liver that plays a central role in cholesterol metabolism.
Tekmira enrolled a total of 23 subjects in its Phase 1 clinical trial. Of the 23 subjects enrolled, 17 subjects received a single dose of ApoB SNALP at one of seven different dosing levels and six subjects received a placebo.
The primary endpoints of the ApoB SNALP Phase 1 clinical trial were measures of safety and tolerability. ApoB SNALP was well tolerated overall in this study with no evidence of liver toxicity, which was the anticipated dose-limiting toxicity observed in preclinical studies. Of the two subjects treated at the highest dose level, one subject experienced flu-like symptoms consistent with stimulation of the immune system caused by the ApoB siRNA payload. The other subject treated at the highest dose level experienced no side effects. Based on the potential for the immune stimulation to interfere with further dose escalation, Tekmira decided to conclude the trial.
Secondary endpoints of the ApoB SNALP Phase 1 clinical trial included measures of drug activity, including the reduction of ApoB protein and LDL cholesterol. Of the two subjects treated at the highest dose, the average transient reduction of ApoB protein and LDL cholesterol was 21.1% and 16.3%, respectively. The complete data set will be presented at an upcoming scientific meeting.
Dr. Mark J. Murray, Tekmira’s President and CEO, said “We are pleased to report the completion of the ApoB SNALP Phase 1 clinical trial. ApoB SNALP was well tolerated with no liver toxicity in any of the subjects treated and we observed some encouraging indications of RNAi drug activity. We have gained a considerable amount of very valuable information and insight and at this time we believe it is prudent to close the current trial and focus our efforts on an improved ApoB SNALP product candidate.”
“With our extensive experience and understanding of siRNA mediated immune stimulation, we are confident we can modify the siRNA payload to avoid this unanticipated side effect. Therefore, we will focus on advancing a new ApoB siRNA in a next generation SNALP formulation that exhibits significantly greater potency and we will be ready to continue clinical development later this year,” added Dr. Murray.
Building on extensive preclinical work and the data obtained in this clinical trial, Tekmira will select a new siRNA payload and SNALP formulation in the first quarter of 2010. Tekmira has made significant improvements in its SNALP formulation technology over the past two years and the new ApoB SNALP formulation will be several fold more potent than the current formulation. Tekmira is targeting the second half of 2010 to re-initiate a Phase 1 clinical trial with its next generation ApoB SNALP.
ApoB SNALP is being developed as a treatment for patients with elevated low-density lipoprotein (LDL) cholesterol, or “bad” cholesterol, who are not well served by current therapy.
Tekmira’s therapeutic approach is to target ApoB, a protein synthesized in the liver that is essential to the assembly and secretion of very low density lipoprotein (VLDL), a precursor to LDL, both of which are required for the transport and metabolism of cholesterol.
ApoB SNALP consists of small interfering RNA (siRNA), designed to silence ApoB, encapsulated in a SNALP formulation. ApoB SNALP is delivered with high efficiency into the liver hepatocytes, the cells which produce ApoB, where the siRNA acts to silence the mRNA coding for ApoB protein resulting in a decrease in circulating VLDL and LDL.
Tekmira enrolled a total of 23 subjects in its Phase 1 clinical trial. Of the 23 subjects enrolled, 17 subjects received a single dose of ApoB SNALP at one of seven different dosing levels and six subjects received a placebo.
The primary endpoints of the ApoB SNALP Phase 1 clinical trial were measures of safety and tolerability. ApoB SNALP was well tolerated overall in this study with no evidence of liver toxicity, which was the anticipated dose-limiting toxicity observed in preclinical studies. Of the two subjects treated at the highest dose level, one subject experienced flu-like symptoms consistent with stimulation of the immune system caused by the ApoB siRNA payload. The other subject treated at the highest dose level experienced no side effects. Based on the potential for the immune stimulation to interfere with further dose escalation, Tekmira decided to conclude the trial.
Secondary endpoints of the ApoB SNALP Phase 1 clinical trial included measures of drug activity, including the reduction of ApoB protein and LDL cholesterol. Of the two subjects treated at the highest dose, the average transient reduction of ApoB protein and LDL cholesterol was 21.1% and 16.3%, respectively. The complete data set will be presented at an upcoming scientific meeting.
Dr. Mark J. Murray, Tekmira’s President and CEO, said “We are pleased to report the completion of the ApoB SNALP Phase 1 clinical trial. ApoB SNALP was well tolerated with no liver toxicity in any of the subjects treated and we observed some encouraging indications of RNAi drug activity. We have gained a considerable amount of very valuable information and insight and at this time we believe it is prudent to close the current trial and focus our efforts on an improved ApoB SNALP product candidate.”
“With our extensive experience and understanding of siRNA mediated immune stimulation, we are confident we can modify the siRNA payload to avoid this unanticipated side effect. Therefore, we will focus on advancing a new ApoB siRNA in a next generation SNALP formulation that exhibits significantly greater potency and we will be ready to continue clinical development later this year,” added Dr. Murray.
Building on extensive preclinical work and the data obtained in this clinical trial, Tekmira will select a new siRNA payload and SNALP formulation in the first quarter of 2010. Tekmira has made significant improvements in its SNALP formulation technology over the past two years and the new ApoB SNALP formulation will be several fold more potent than the current formulation. Tekmira is targeting the second half of 2010 to re-initiate a Phase 1 clinical trial with its next generation ApoB SNALP.
ApoB SNALP is being developed as a treatment for patients with elevated low-density lipoprotein (LDL) cholesterol, or “bad” cholesterol, who are not well served by current therapy.
Tekmira’s therapeutic approach is to target ApoB, a protein synthesized in the liver that is essential to the assembly and secretion of very low density lipoprotein (VLDL), a precursor to LDL, both of which are required for the transport and metabolism of cholesterol.
ApoB SNALP consists of small interfering RNA (siRNA), designed to silence ApoB, encapsulated in a SNALP formulation. ApoB SNALP is delivered with high efficiency into the liver hepatocytes, the cells which produce ApoB, where the siRNA acts to silence the mRNA coding for ApoB protein resulting in a decrease in circulating VLDL and LDL.
