Biotech Values

[DewDiligence]

GSK Starts 15,000-Patient Phase-3 Study of Darapladib in Chronic Heart Disease

[This PR is from HGSI, the licensor; GSK’s own PR is embedded in it. The trial is event-driven; the final analysis triggered by 1,500 MACE events (i.e. 10% of the total enrolled patients) is expected to occur in approximately three years. A second phase-3 trial in post-ACS patients is planed to start in 2009. HGSI gets a 10% royalty on worldwide sales.]

http://finance.yahoo.com/news/FYI-from-Human-Genome-prnews-13867285.html

›Thursday December 18, 2008, 10:09 am EST

ROCKVILLE, Md., Dec. 18 /PRNewswire-FirstCall/ -- Attached is a press release issued earlier this morning by GlaxoSmithKline, announcing that GSK has initiated the first pivotal trial to evaluate the efficacy of long-term treatment with the investigational Lp-PLA2 inhibitor darapladib in men and women with chronic coronary heart disease.

Darapladib was discovered by GSK based on HGS technology. HGS will receive 10% royalties on worldwide sales if darapladib is commercialized, and has a 20% co-promotion option in North America and Europe.

All inquiries regarding the Phase 3 study of darapladib should be directed to the contacts provided by GSK.

[GSK’s PR follows]:

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GSK initiates phase III programme for novel cardiovascular medication, darapladib

Thursday 18 December 2008, London, UK

GlaxoSmithKline today announced initiation of the first pivotal Phase III clinical trial to evaluate the efficacy of long-term treatment with the investigational Lp-PLA2 inhibitor darapladib in men and women with chronic coronary heart disease (CHD). The study, called STABILITY (STabilisation of Atherosclerotic plaque By Initiation of darapLadIb TherapY) will include more than 15,000 patients from 39 countries.

"Despite major advances in medical treatment, coronary heart disease remains the leading cause of death worldwide and new approaches are needed to help reduce this burden to patients and society," said Patrick Vallance, MD., Senior Vice President, Drug Discovery, GlaxoSmithKline. "GSK is initiating the large STABILITY trial with darapladib as part of a phase III programme to determine if this novel medication could improve people's lives by reducing the risk of cardiovascular events."

STABILITY is a randomised, placebo-controlled, double-blind, parallel group multi-center, event-driven trial in men and women with chronic CHD. The study will evaluate the clinical efficacy of long-term treatment with darapladib as compared with placebo (when both are added to standard of care which may include a statin, aspirin and blood pressure medications) on the incidence of first occurrence of major adverse cardiovascular events (MACE), including CV death, non-fatal heart attack and non-fatal stroke.

"The recently completed IBIS-2 study (Integrated Biomarker and Imaging Study-2) showed that use of darapladib dramatically reduced Lp-PLA2 activity in plasma and prevented expansion of the necrotic core - a region within coronary artery plaques associated with a high risk of rupture which is the major cause of heart attacks and cardiovascular death," said Harvey White, MD, co-chair of the Steering Committee for STABILITY and director of Coronary Care and Cardiovascular Research Unit, Auckland City Hospital, Auckland, New Zealand. "STABILITY will help us to determine whether treatment with darapladib is in fact associated with favourable effects on these outcomes as well as stroke."

Coronary artery disease is the leading cause of death globally1 and the single largest killer of Americans.2 According to the World Health Organization (WHO), 7.2 million people worldwide die each year from CAD.3 Advances in science, clinical medicine, and public health over the past 50 years have resulted in significant reductions in the age-adjusted death rates from coronary heart disease and stroke, however, the clinical event rates associated with atherosclerosis have largely remained unchanged over the past 30 years. 4

About STABILITY and the Phase III programme

In STABILITY, men and women with chronic CHD and receiving standard of care will be randomised 1:1 to once-daily treatment with darapladib or placebo. The duration of the study will be determined by the rate of first occurrence of events that comprise the primary endpoint of MACE. The study will be stopped when approximately 1500 reports of first occurrence of MACE have occurred - estimated to be approximately three years - with interim independent analyses planned.

The study's secondary objectives are to evaluate the efficacy of darapladib on major and total coronary events, including CHD death, non-fatal heart attack, urgent and non-urgent coronary revascularisation, or hospitalisation for unstable angina, individual components of MACE and all-cause mortality. Additional safety and efficacy data will also be collected. Pre-specified sub-studies will include 24-hour ambulatory blood pressure monitoring, progression of protein in urine, changes in cognitive function and pharmacokinetic analyses.

GSK is also planning to initiate another large event-driven trial with darapladib in late 2009 in a post-ACS patient population. ACS represents a spectrum of clinical presentations (unstable angina, non-ST segment elevation MI, ST segment elevation MI) that are associated with an increased risk of CV death, non-fatal MI and recurrent hospital admissions for refractory myocardial ischemia.

About darapladib and Lp-PLA2

Darapladib is a selective and orally active inhibitor of LpPLA2 currently in Phase III development as a potential anti-atherosclerosis agent for the reduction of major cardiovascular events in patients with coronary heart disease. In four completed Phase II studies, 1051 patients have received darapladib for periods of up to 12 months, and 371 subjects have received darapladib 160 mg once daily for 12 weeks or longer.

Lp-PLA2 is an enzyme found in blood and atherosclerotic plaque. The underlying process in most heart attacks and strokes is atherosclerosis, which is an inflammatory disease characterised by the build-up of plaque within the walls of arteries. The rupture of unstable atherosclerotic plaque, regardless of the size of the plaque, causes most heart attacks and strokes. Elevated Lp-PLA2 activity has been implicated in the development and progression of atherosclerosis. Large amounts of Lp-PLA2 are present in the necrotic core of rupture-prone human coronary plaques.
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