Update on Merck's development programs for vorapaxar, ER niacin/laropirprant and anacetrapib

MerckAug 27 2012

Merck (known outside the United States and Canada as MSD) today provided an update on the development programs for vorapaxar, extended release niacin/laropirprant (MK524A, Tredaptive) and anacetrapib in association with the European Society of Cardiology (ESC) meeting in Munich.

Vorapaxar: Merck now plans to file regulatory applications in 2013

Following a review of the clinical trial data and discussions with external experts, Merck now plans to file applications for vorapaxar, an investigational anti-thrombotic medicine in the United States and the European Union in 2013. Merck plans to seek an indication for the prevention of cardiovascular events in patients with a history of heart attack and no history of TIA (transient ischemic attack) or stroke. Discussions with worldwide regulatory agencies are continuing and we will update this information when appropriate.

Extended release niacin/laropiprant (MK-524A, Tredaptive): Merck confirms study on track to complete later this year

For MK-524A (Tredaptive), Merck also confirmed that the HPS2-THRIVE (Treatment of HDL to Reduce the Incidence of Vascular Events) study is on track to complete later this year, and Merck plans to file in the United States and the European Union in 2013.

Anacetrapib: Merck provides information about a different method to measure LDL cholesterol and progress on REVEAL study

Merck also today provided information about a different method to more accurately measure LDL-C when patients are treated with anacetrapib, an investigational CETP-inhibitor. Based on this method, called beta-quantification, anacetrapib 100 mg daily resulted in LDL-C reductions of approximately 25 to 35 percent, compared to the 40 percent reduction previously reported from the DEFINE (Determining the EFficacy and Tolerability of CETP INhibiition with AnacEtrapib) study and other anacetrapib studies.

In DEFINE, LDL-C was calculated using the Friedewald equation, which is the method used in most lipid studies. The Friedewald method estimates LDL-C from direct measurements of total cholesterol, HDL-C and triglycerides, but does not measure LDL-C directly. Because CETP-inhibition increases the ratio of triglycerides to cholesterol in LDL and VLDL particles, Merck and the DEFINE Steering Committee hypothesized that methods other than Friedewald might more accurately measure LDL-C when lowered by CETP inhibitors. The researchers believe that these initial results indicate that the beta-quantification method provides a more accurate measure of LDL-C after treatment with anacetrapib. These findings are being finalized and will soon be submitted for publication in a peer-reviewed journal, and additional studies are underway, or planned, to more precisely determine the LDL-C lowering of anacetrapib.

The results of other key lipid measurements such as HDL-C, triglycerides, and apo-lipoproteins, such as A-I and B, are not believed to be affected by this observation. As previously reported in DEFINE, at 24 weeks, anacetrapib increased HDL-C by 138 percent. Compared to placebo, anacetrapib raised mean apo-lipoprotein (apo) A-1 (a major protein component of HDL particles) by 45 percent, lowered mean apo B (a major protein component of atherogenic lipoprotein particles, including LDL) by 21 percent, and reduced mean non-HDL-C by 32 percent. Anacetrapib reduced median Lp(a) (an LDL-like particle) by 36 percent compared to placebo.

Based on the available data, REVEAL investigators are not planning to change the size or duration of REVEAL ((Randomized EValuation of the Effects of Anacetrapib through Lipid-modification), the event-driven cardiovascular clinical outcomes trial of anacetrapib. REVEAL is being led by Oxford University's Clinical Trial Service Unit, and is one of the largest cardiovascular studies ever conducted. The study started in June 2011 and will enroll 30,000 patients with pre-existing vascular disease. Oxford researchers reported today that more than 20,000 patients have now been enrolled in the trial, and that the study is on track to achieve target recruitment during 2013. The study is predicted to be completed in 2017.

"Merck remains committed to research to bring forward innovations in cardiovascular disease, which remains the leading cause of death worldwide," said Jeff Chodakewitz, M.D., senior vice president, Late Stage Development, Merck Research Laboratories. "The clinical outcomes studies for these three medicines have involved or will involve more than 90,000 patients around the world. All of these studies are designed to address the important question of whether, by adding these medicines to the current standard of care, we can further reduce the risk of cardiovascular events."