Date: 2015-06-03
Type of information: Publication of results in a medical journal
phase: 2b
Announcement: publication of results in The Lancet
Company: Dezima Pharma (The Netherlands)
Product: DEZ-001 - TA-8995
Action
mechanism: cholesteryl ester transfer protein (CETP) inhibitor. DEZ-001 is a cholesteryl ester transfer protein (CETP) inhibitor that has already demonstrated clinically relevant improvements on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels as well as other lipid parameters in healthy volunteers. The Cholesteryl Ester Transfer Protein (CETP) facilitates the transfer of cholesterol from HDL to other lipoproteins including LDL, in exchange for triglycerides. The CETP mediated transfer of cholesterol into LDL particles results into maturation of those LDL particles to more atherogenic LDL particles, which contribute to macrophage foam cell, and eventually plaque formation. Large Mendelian Randomization studies, epidemiological as well as preclinical studies have provided evidence for the notion that lower CETP activity is inversely related to cardiovascular mortality. In addition, reduced activity of CETP by pharmaceutical means or by naturally occurring mutations in the CETP gene results in increased HDL and decreased LDL levels. This provides a rationale for the inhibition of CETP activity as a therapeutic intervention in dyslipidemic conditions characterized by either low HDL or high LDL cholesterol. The compound was in-licensed from Mitsubishi Tanabe Pharma Corporation.
Disease: dyslipidemia
Therapeutic area: Cardiovascular diseases
Country: Denmark, The Netherlands
Trial
details: The TULIP (“TA-8995: its Use in patients with mild dysLIPidemia”) study takes place in specialized centres across Denmark and the Netherlands. The aim of the study is to investigate the effects of TA-8995 (DEZ-001), a potential best-in-class CETP inhibitor, in around 360 patients with mild dyslipidemia on a wide range of plasma lipids, lipoproteins and validated biomarkers of cardiovascular disease (CVD). Recruitment started in August 2013. The study has seen rapid enrolment in 17 specialized centres across the Netherlands and Denmark. The study has nine arms with patients receiving TA-8995 alone and in combination with statins.
Latest
news: * On June 3, 2015, Dezima Pharma the biotechnology company developing innovative drugs in the field of dyslipidemia, today announced the publication of the phase 2b TULIP study results with its CETP inhibitor, TA-8995, in the Lancet. The peer-reviewed article is entitled “Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomised, double-blind, placebo-controlled phase 2 trial”. The TULIP (“TA-8995: its Use in patients with mild dysLIPidaemia”) study was conducted in specialized cardiovascular centres across Denmark and the Netherlands. A total of 364 individuals with dyslipidaemia were randomised into nine cohorts: placebo, TA-8995 as monotherapy at different doses, or in combination with different statins. The study investigated the effects of TA-8995 on a wide range of established cardiovascular disease (CVD) biomarkers over a three month dosing period. The results showed potent effects on the primary endpoint, which was a composite of change from baseline in LDL-C and HDL-C. 5 mg of TA-8995 reduced LDL-C by 45% and increased HDL-C by 161%. 10 mg of TA-8995 in combination with statin therapy reduced LDL-C by an additional 48%. With this combination therapy nearly all patients achieved the most stringent LDL-C target of <1.8 mmol/L. In addition, TA-8995 boosted cholesterol efflux significantly. Finally, TA-8995 was safe and well tolerated without any drug accumulation as has been reported with other CETP inhibitors. The Company anticipates starting a phase 3 cardiovascular outcomes trial in the first half of 2016. * On August 29, 2014, Dezima Pharma announced that it has received very positive results in its Phase 2b TULIP clinical trial, a double blind, placebo controlled, Phase 2b dose ranging study of TA-8995 (DEZ-001), as monotherapy and in combination with statins for treating dyslipidemia. A total of 364 patients were randomised into nine cohorts; a placebo, TA-8995 alone at different doses, or in combination with different statins. The study investigated the effects of TA-8995 on a wide range of established cardiovascular disease (CVD) biomarkers over a three months' dosing period. The results showed dramatic effects on the primary endpoint, which was a composite of changes in lowering LDL-C and raising HDL-C, as well as strong and clinically relevant effects on other parameters including cholesterol efflux and Lipoprotein(a) (Lp(a)). There were no safety or tolerability issues identified or any pharmacokinetic concerns about potential accumulation of the drug. The company plans to publish the full data over the coming months in peer reviewed journals. Meanwhile Dezima will continue to collect data from its ongoing studies (DDI, TQT and a pilot study on Lp(a)), while preparing for the start of pivotal Phase 3 studies in 2015. * On January 13, 2014, Dezima Pharma has announced the completed enrolment of its phase 2b TULIP study. The aim of the study is to investigate the effects of TA-8995 (DEZ-001), a potential best-in-class CETP inhibitor, in around 360 patients with mild dyslipidemia on a wide range of plasma lipids, lipoproteins and validated biomarkers of cardiovascular disease (CVD). Recruitment started in August 2013. In addition, Dezima Pharma is currently preparing and executing a range of pre-clinical and clinical phase 3 enabling studies around its lead product, including a DDI study and a TQT study under an IND, in order to have a comprehensive partnering package. In phase 1 studies, TA-8995 has also shown a potent effect on Lp(a), an independent, major risk factor for cardiovascular disease. * On August 29, 2013, Dezima Pharma has announced the initiation of a double blind, placebo controlled, Phase 2b dose ranging study of DEZ-001 (previously TA-8995), alone and in combination with statins, in order to study the effects on a wide range of lipids and other biomarkers of cardiovascular disease (CVD) in patients with mild dyslipidaemia. Dezima Pharma was founded in 2012 by John J.P. Kastelein, Professor of Medicine at the Department of Vascular Medicine at the Academic Medical Centre, University of Amsterdam. The Company recently raised €14.2m from a Series A financing with participation of Forbion Capital Partners, BioGeneration Ventures and New Science Ventures, and a loan from the AgentschapNL, an agency of the Dutch Ministry of Economic Affairs. Dezima Pharma focuses on the development of novel products to treat dyslipidemic patients suffering from cardiovascular disease. Its lead program DEZ-001 involves the development of the CETP inhibitor TA-8995, which was in-licensed from Mitsubishi Tanabe Pharma Corporation.
