RG7652 / Roche - LARVOL DELTA

Ceramide-phospholipid risk score associates with cardiovascular events and is lowered by atorvastatin, simvastatin and anti-PCSK9 treatments. (PubMed, J Cardiovasc Pharmacol) - "Selected ceramides and phospholipids were analyzed with a quantitative liquid chromatography-mass spectrometry-based method from plasma or serum samples obtained from the Angiography and Genes study (ANGES, N = 966), and placebo-controlled trials investigating atorvastatin and simvastatin (N = 44) and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor RG7652 (N = 78). The CERT2 risk score is a significant predictor of cardiovascular outcomes in all-comer patients with symptomatic or suspected coronary heart disease. Treatment with lipid-lowering medication significantly lowers the CERT2 risk score."

Journal • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Heart Failure • Myocardial Infarction • Venous Thromboembolism

A Systematic Review and Meta-Analysis of Therapeutic Efficacy and Safety of Alirocumab and Evolocumab on Familial Hypercholesterolemia. (PubMed, Biomed Res Int) - "A computer was used to search the electronic Cochrane Library, PubMed/MEDLINE, and Embase databases for clinical trials using the following search terms: "AMG 145", "evolocumab", "SAR236553/REGN727", "alirocumab", "RG7652", "LY3015014", "RN316/bococizumab", "PCSK9", and "familial hypercholesterolemia" up to November 2020. Moreover, no significant difference was found between PCSK9-mAbs treatment and placebo in common adverse events, serious events, and laboratory adverse events. PCSK9-mAbs significantly decreased LDL-C and other lipid levels with satisfactory safety and tolerability in FH treatment."

Journal • Retrospective data • Review • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders • APOA1 • APOB

Roche holdings: Revised $58 price estimate on strong pipeline (Nasdaq) - "The company's experimental cardiovascular drug, RG7652, is moving toward advanced trials after significantly reducing levels of bad LDL cholesterol."

Commercial • Dyslipidemia

Oppenheimer Healthcare Conference (Roche) - Anticipated filing for metabolic diseases in 2017 or later

Anticipated regulatory • Dyslipidemia

Roche’s secret heart drug moves toward late-stage trial (Businessweek) - Roche is enrolling pts in a mid-stage trial of the drug; In 2013, the company plans to begin P3 clinical testing needed before seeking regulatory approval; Sanofi & partner Regeneron, Amgen & Pfizer are among the companies working on similar medicines targeting the PCSK9 gene; Anti-PCSK9 drugs could help some 1.5M Americans who aren’t able to take statins, or as many as 11M people including those whose cholesterol doesn’t go low enough on a statin

Anticipated new P3 trial • Dyslipidemia

Effect of RG7652, a mAb against PCSK9, on apolipoprotein B, oxidized LDL, lipoprotein(a) and lipoprotein-associated phospholipase A2 in healthy individuals with elevated LDL-c (AHA 2013) - Presentation time: Monday, Nov 18, 2013, 5:00 PM - 7:00 PM; Abstract # 12009; P=NA, N=80; “RG7652 treatment resulted in a dose-related reduction in serum ApoB and OxLDL by up to 50% from baseline. In the 800 mg single-dose cohort, mean levels of both ApoB and OxLDL remained suppressed by 45% 2 months after RG7652 administration. A single dose of RG7652 reduced serum Lp(a) levels in a dose-related manner with a mean 45% reduction following a 800 mg dose.”

Clinical data • Atherosclerosis • Dyslipidemia

Effects of RG7652, a fully human mAb against proprotein convertase subtilisin/kexin type 9, on LDL-c: A Phase I, randomised, double-blind, placebo-controlled, single- and multiple-dose study (ESC 2013) - Presentation time: 2 Sep 14:00 - 18:00; Abstract # P4183; P1, N=80; “RG7652 reduced mean LDL-c by as much as 90 mg/dL (60%) from baseline...average reduction in LDL-c at Day 15 in SD and Day 36 in MD was >40 mg/dL in all cohorts other than the lowest dose...Thirty-seven AEs, all mild, were attributed to study drug: 27 in 14 RG7652 subjects; 10 in 6 placebo subjects.”

P1 data • Atherosclerosis • Dyslipidemia

Chugai: Annual Report 2014 (Chugai) - “Chugai has stopped development of RG7652, an anti-PSCK9 human monoclonal antibody, following Roche’s discontinuation of development”

Discontinued • Dyslipidemia

Roche: Annual Results 2012 (Roche) - Anticipated presentation of data from P1 trial for metabolic diseases in 2013; Anticipated data from P2 EQUATOR trial for metabolic diseases in 2013

Anticipated P1 data • Anticipated P2 data • Dyslipidemia

Roche: Union Investment/DVFA, Innovative Strategies in the Life Sciences Sector (Roche) - Anticipated NME submission in US and EU for metabolic diseases in 2016 or later

Anticipated EU regulatory • Anticipated FDA event • Dyslipidemia

Impact of PCSK9 monoclonal antibodies on circulating hs-CRP levels: a systematic review and meta-analysis of randomised controlled trials. (PubMed, BMJ Open) - "Our updated meta-analysis suggested that PCSK9-mAbs had no significant impact on circulating hs-CRP levels irrespective of PCSK9-mAb types, participant characteristics and treatment duration or methods."

Journal • Retrospective data • Review