Basel, 1 April 2011
Dalcetrapib Phase II studies dal-VESSEL and dal-PLAQUE show encouraging results
Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the results from two exploratory Phase IIb studies, dal-VESSEL and dal-PLAQUE, further support the promising safety profile of dalcetrapib, its first-in-class cholesteryl ester transfer protein (CETP) modulator. The studies investigated dalcetrapib’s effects on vascular function (dal-VESSEL) and on atherosclerotic disease progression (dal-PLAQUE) with the main goal of confirming that dalcetrapib does not have pro-inflammatory or pro-atherogenic effects, does not affect blood pressure and is generally well tolerated by patients treated for up to two years.
Although current therapies are effective at treating many cardiovascular (CV) risk factors, CV disease remains the leading cause of mortality worldwide. A major cause of CV morbidity and mortality is atherosclerosis, a disease in which cholesterol accumulates in plaques within the arterial wall. High density lipoprotein (HDL) removes cholesterol from atherosclerotic plaques therefore drugs that improve this functionality may slow the progression of atherosclerosis and prevent CV events.
Dalcetrapib is an innovative molecule which increases the ‘good’ functional HDL-cholesterol (HDL-C) by modulation of CETP. The hypothesis that dalcetrapib may prevent future CV events is currently being tested in the dal-HEART Program in more than 17,000 patients.
“We are pleased with the results of dal-PLAQUE and dal-VESSEL and we look forward to presenting the details of these studies at a future medical meeting”, said Hal Barron M.D., Chief Medical Officer and Head, Global Product Development. "To evaluate whether there is a clinical benefit of dalcetrapib, we need to await the results of the ongoing Phase III study (dal-OUTCOMES) to determine if dalcetrapib can reduce heart attacks and strokes in patients with CV disease.”
In dal-VESSEL, the primary efficacy objective was to evaluate the effect of dalcetrapib on endothelial function using brachial flow-mediated dilatation1 (FMD) in patients receiving either dalcetrapib or placebo on top of their standard medication after 12 weeks’ treatment. FMD is a response of an intact endothelium and impairment of FMD is a validated marker of endothelial dysfunction, a process associated with the development of atherosclerosis. The primary safety objective of the dal-VESSEL study was to evaluate the effect of dalcetrapib on blood pressure as measured by 24-hour ambulatory blood pressure monitoring assessed at week 4. Patients were treated for a total period of 36 weeks.
In dal-PLAQUE, the primary objective was to assess the effect of dalcetrapib on atherosclerotic plaque inflammation at 6 months using PET/CT2 and on plaque burden/progression after 12 months using MRI3, comparing patients receiving dalcetrapib or placebo in addition to standard medication. Patients received treatment for 24 months
Data from both studies support the ongoing dal-HEART Program and will be presented at a future medical meeting.
A Phase III morbidity and mortality study, dal-OUTCOMES, in patients with stable coronary heart disease who had experienced a recent acute coronary event aims to evaluate dalcetrapib’s effect on the reduction of cardiovascular events beyond and above the current standard of care. In total 15,872 patients have been enrolled.
A Phase III study, dal-ACUTE, the fifth study in the dal-HEART Program is currently being initiated. This study will evaluate the safety and efficacy of dalcetrapib in approximately 300 patients treated early after an acute coronary syndrome for a period of 20 weeks.
Dalcetrapib was in-licenced by Roche from Japan Tobacco, Inc. in late 2004. Roche acquired exclusive worldwide rights to develop and commercialise dalcetrapib, excluding Japan, where Japan Tobacco has retained these rights. The collaboration with Japan Tobacco is a successful partnership and the companies have a very positive working collaboration.
Flow mediated dilatation1: expansion of a vessel in response to increased blood flow
PET/CT2: Positron emission tomography/computed tomography – imaging technique to assess inflammatory processes in the wall of blood vessels
MRI3: Magnetic resonance imaging – technique to characterize atherosclerotic plaque burden
Dalcetrapib is a CETP modulator, which raises functional HDL by modulating CETP activity through a mechanism which differs from other CETP inhibitors, including torcetrapib.
The HDL raised by dalcetrapib promoted efflux of cholesterol from cells in animal experiments. The hypothesis that it will similarly remove cholesterol from atherosclerotic plaques in humans, potentially reducing the occurrence of cardiovascular events, is currently being tested in Phase III studies.
dal-VESSEL is a phase IIB, randomised, double-blind, placebo-controlled study in patients with coronary heart disease (CHD), or CHD risk equivalents. 476 patients with HDL-C levels <50 mg/dL were recruited and received dalcetrapib 600 mg/day or placebo in addition to their existing treatments. The primary efficacy endpoint is change from baseline in brachial flow mediated dilatation after 12 weeks. The primary safety endpoint was 24-hour ambulatory blood pressure monitoring (ABPM) assessed at week 4..
dal-PLAQUE is a phase IIB, exploratory, randomised, double-blind, placebo-controlled study in patients with CHD, or CHD risk equivalents. 130 patients were recruited and received dalcetrapib 600 mg/day or placebo in addition to their existing treatments. The primary outcomes were the effect of dalcetrapib on positron emission tomography (PET) at 6 months, and magnetic resonance imaging (MRI) plaque burden after 12 months. Secondary objectives include PET at 3 months and MRI at 6, and 24 months.
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2010, Roche had over 80’000 employees worldwide and invested over 9 billion Swiss francs in R&D. The Group posted sales of 47.5 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.
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