Tredaptive (niacin controlled release/laropiprant) / Merck (MSD) - LARVOL DELTA

A Systematic Review of Cost-Effectiveness of Non-Statin Lipid-Lowering Drugs for Primary and Secondary Prevention of Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus. (PubMed, Curr Probl Cardiol) - "Thirteen studies were included; ezetimibe (n=8), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (n=4), fenofibrate (n=2), nicotinic acid (n=1), extended-release niacin/laropiprant (ER- ERN/LRPT) (n=1), and icosapent ethyl (n=1). Nicotinic acid and ER- ERN/LRPT compared to statin monotherapy were also cost-effective. Icosapent ethyl using the solid-state relay was cost-effective compared to standard care but not using the wholesale acquisition cost."

HEOR • Journal • Review • Cardiovascular • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Effect of switch to the highest dose of rosuvastatin versus add-on-statin fenofibrate versus add-on-statin nicotinic acid/laropiprant on oxidative stress markers in patients with mixed dyslipidemia (Cardiovasc Ther) - P4, N=100; NCT01010516; “...both ox-LDL and urine F2-isoprostane levels decreased similarly in the add-on ER-NA/LRPT and rosuvastatin monotherapy group, while a less pronounced decrease was observed in the add-on fenofibrate group.”

P4 data • Atherosclerosis • Dyslipidemia

Merck announces HPS2-THRIVE study of Tredaptive (Extended-release niacin/laropiprant) did not achieve primary endpoint (Merck (MSD)) - P3, N=25,673; HPS2-THRIVE; Based on the current understanding of the new data & until further analyses can be completed, Merck is recommending that providers not start new pts on Tredaptive; Merck does not plan to seek regulatory approval for the medicine in the US.

Anticipated regulatory • P3 data • Dyslipidemia

Efficacy and safety of extended release (ER) niacin/laropiprant when added to ongoing lipid-modifying therapy in patients with high cholesterol or abnormal lipid levels (protocol MK-0524A-133 AM2) (clinicaltrials.gov) - P3, N=1,134; Sponsor: Merck; Active, not recruiting -> Terminated.

Trial termination • Dyslipidemia

Following stable therapy with extended release niacin/laropiprant, continued extended release niacin/laropiprant use redu ced flushing versus extended release niacin alone in dyslipidemic patients (AHA 2011) - Presentation Time: Tuesday, Nov 15, 2011, 4:00 PM - 4:08 PM; P=NA, N=1,152; Extended-release niacin (ERN) / laropiprant (LRPT) produced significantly less flushing relative to ERN alone during the post-withdrawal period, as measured by the number of days/week with GFSS ≥4 (p<0.001) and the percentage of patients with maximum GFSS ≥4 (ERN/LRPT: 19.6%; ERN: 48.9%; Placebo: 9.2%); There were fewer drug related adverse experiences during the post-withdrawal period comparing the ERN/LRPT to the ERN treatment groups

Clinical data • Dyslipidemia

Detrimental effects of niacin/laropiprant on microvascular reactivity and red cell deformability in patients with elevated lipoprotein(a) levels. (PubMed) - "In the light of the results of HPS2-THRIVE study, we may hypothesize that the addition of laropiprant to niacin might be responsible for these negative effects. In turn, these effects might explain, at least in part, the lack of a clinical net benefit of niacin/laropiprant in the trial."

Journal • Biosimilar

The law firms of Bernstein Litowitz Berger & Grossmann LLP and Grant & Eisenhofer P.A. announce pendency of class action in In re Merck & Co., Inc. Vytorin / Zetia securities litigation (Market Watch) - The trial is scheduled by the court to begin on Mar 4, 2013.

Corporate lawsuit • Dyslipidemia

Merck highlights pipeline progress and showcases novel innovations at R&D and business briefing (Merck (MSD)) - The company plans to submit eight new US filings in 2012-2013, including Tredapyive (ER niacin/laropiprant); Anacetrapib is being investigated in a large P3 outcomes study, the REVEAL study, for the treatment of atherosclerosis; This candidate is anticipated to be filed after the results of the study become available; results from REVEAL are expected after 2015

Pipeline update • Cardiovascular • Dyslipidemia

HPS2-THRIVE randomized placebo-controlled trial in 25,673 high-risk patients of ER niacin/laropiprant: Trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment (Eur Heart J) - P3, N=25,673; PMID: 23444397; NCT00461630; "The risk of myopathy was increased by adding ERN/LRPT to simvastatin 40 mg daily (with or without ezetimibe), particularly in Chinese patients whose myopathy rates on simvastatin were higher. Despite the side effects of ERN/LRPT, among individuals who were able to tolerate it for ∼1 month, three-quarters continued to take it for ∼4 years."

P3 data • Dyslipidemia