MDCO-216 / Novartis - LARVOL DELTA

Efficacy of Apolipoprotein A-1 Infusion on Coronary Atherosclerosis Postacute Coronary Syndrome: A Network Meta-Analysis of Randomized Controlled Trials. (PubMed, Cardiol Rev) - "Our analysis concludes that ETC-216, 45 mg, showed a significant reduction in PAV. This analysis highlights the need for further clinical trials to explore this regimen for enhancing responses in ACS patients."

Journal • Retrospective data • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease • APOA1

Impact of Apolipoprotein A-1 Infusion on Coronary Atherosclerosis Post-Acute Coronary Syndrome: A Network Meta-Analysis of randomized controlled trials. (AHA 2024) - "Our analysis concludes that ETC-216, 45 mg showed a significant reduction in PAV. Other regimens were insignificant in their effect on atheroma reduction. This analysis highlights the need for further clinical trials to explore this regimen for enhancing responses in ACS patients."

Retrospective data • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Myocardial Infarction • APOA1

ApoA-I Infusion Therapies Following Acute Coronary Syndrome: Past, Present, and Future. (PubMed, Curr Atheroscler Rep) - "Phase II-b studies of MDCO-216 and CER-001 failed to produce a significant reduction in coronary plaque volume as assessed by IVUS. However, the investigation to determine whether the direct infusion of a reconstituted apoA-I reduces post-myocardial infarction coronary events is being tested using CSL112, which is dosed at a higher level than MDCO-216 and CER-001 and has more favorable pharmacodynamics."

Journal • Review • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Dyslipidemia • Myocardial Infarction • APOA1

Artificial high-density lipoprotein-mimicking nanotherapeutics for the treatment of cardiovascular diseases. (PubMed, Wiley Interdiscip Rev Nanomed Nanobiotechnol) - "Because of the pleiotropic endothelial protective effects of high-density lipoproteins (HDL), the direct infusion of reconstituted HDL (rHDL) products, including MDCO-216, CER001, and CSL112, have been tested in clinical trials to determine whether direct infusion of rHDL can reduce coronary events in CVD patients. Moreover, success stories, lessons, and interpretations of the utility and functionality of these HDL-mimicking nanotherapeutics will be an integral part of this article. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease."

Journal • Review • Cardiovascular • Dyslipidemia

Administration of apo A-I (Milano) nanoparticles reverses pathological remodelling, cardiac dysfunction, and heart failure in a murine model of HFpEF associated with hypertension. (PubMed, Sci Rep) - "MDCO-216 completely reversed cardiac dysfunction and abolished heart failure as evidenced by the normal lung weight and normal biomarkers of heart failure. In conclusion, apo A-I nanoparticles constitute an effective treatment for established hypertension-associated HFpEF."

Journal • Preclinical • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Hypertension • Immunology

The Medicines Company: Goldman Sachs Global Healthcare Conference (The Medicines Company Press Release) - Anticipated initiation of P1 trial for acute coronary syndrome in H2 2013

Anticipated trial initiation date • Acute Coronary Syndrome

The Medicines Company: Annual Report 2013 (The Medicines Company) - Anticipated expiry of patent in US for use in the treatment of acute coronary syndrome in October 2024

Anticipated patent expiry • Acute Coronary Syndrome • Dyslipidemia

Reconstituted HDL (Milano) Treatment Efficaciously Reverses Heart Failure with Preserved Ejection Fraction in Mice. (PubMed, Int J Mol Sci) - "...This study investigated whether feeding coconut oil (CC diet) for 26 weeks in female C57BL/6N mice induces HFpEF and evaluated the effect of reconstituted high-density lipoprotein (HDL) (MDCO-216) administration on established HFpEF...In conclusion, the CC diet induced HFpEF. Reconstituted HDL reversed pathological remodeling and functional cardiac abnormalities."

Journal • Preclinical • Biosimilar • Cardiovascular • Fibrosis • Heart Failure • Immunology

Interplay between cigarette smoking and pulmonary reverse lipid transport. (PubMed, Eur Respir J) - "In mice, the capacity of bronchoalveolar lavage fluid and serum to stimulate cholesterol efflux in macrophages was increased after a single exposure to cigarette smoke. ApoA-1(-/-) mice showed increased lung neutrophilia, larger macrophages and greater loss in lean mass in response to smoking, whereas treatment with MDCO-216 reduced the size of macrophages and increased the lean mass of mice exposed to cigarette smoke.Altogether, this study shows a functional interaction between smoking and reverse lipid transport, and opens new avenues for better understanding the link between metabolic and pulmonary diseases related to smoking."

Journal • Biosimilar

The Medicines Company: Q2 FY 2015 Results (The Medicines Company) - Anticipated data from clinical trial to affirm cholesterol efflux and efflux saturation and to assess ultrasound-measured plaque regression in Q1 2016

Anticipated clinical data • Dyslipidemia

The Medicines Company: Investor & Analyst Day (The Medicines Company) - Anticipated initiation of P2 dose finding trial for atherosclerosis in Q2 2015; Anticipated data for P2 dose finding trial for atherosclerosis in Q2 2016; Anticipated publication of P1 data for atherosclerosis in Q1 2015

Anticipated new P2 trial • Anticipated P1 data • Anticipated P2 data • Dyslipidemia

The Medicines Company: Annual Report 2015 (The Medicines Company) - Anticipated expiry of patent in US for use in the treatment of acute coronary syndrome in March 2025; Anticipated expiry of patent in EU for use in the treatment of acute coronary syndrome in October 2024 

Anticipated patent expiry • Dyslipidemia

The Medicines Company discontinues development of MDCO-216, its investigational cholesterol efflux promoter (The Medicines Company Press Release) - P1/2, N=120; NCT02678923; "The Medicines Company announced today the immediate discontinuation of the clinical development program for MDCO-216, its investigational cholesterol efflux promoter. Data from the recently-completed MILANO-PILOT trial did not show drug effects on intracoronary atherosclerotic plaque sufficient to warrant further development...The Company is supporting the close-out of the MILANO-PILOT trial and results will be presented...in the Late-Breaking Clinical Trial Session at the American Heart Association (AHA) Scientific Sessions 2016, on November 15, 2016, in New Orleans."

Anticipated conference • Anticipated P1/2 data • Discontinued • Dyslipidemia

Jefferies Global Healthcare Conference (The Medicines Company) - MDCO - 216 / The Medicine Company; Anticipated data presentation at AHA for PK/PD with new product in Nov 14 '11

Anticipated data presentation • Dyslipidemia • None

A single infusion of MDCO-216 (ApoA-1 Milano/POPC) induces marked changes on the lipid profile (AHA 2014) - Presentation time: November 16, 2014, 9:30 - 11:00 AM; Abstract #9907; P1, N=48; "In both healthy volunteers and stable CAD patients, dose dependent increases in ApoA-1, phospholipid and prebeta-1 HDL and decreases in Apo E were observed. Prominent sustained increases in triglyceride and decreases in HDL-C occurred at doses above 20 mg/kg in healthy volunteers and patients with CAD. In both subject populations, profound increases in ABCA1 mediated cholesterol efflux were observed."

P1 data • Atherosclerosis • Dyslipidemia

MDCO-216 (Apo A-I Milano/POPC Complex) administered to cynomolgus monkeys induces pronounced changes in plasma lipids and apolipoproteins (AHA 2011) - Presentation Time: Monday, Nov 14, 2011, 3:00 PM - 4:30 PM; MDCO-216 increased the level of free cholesterol (by over 10-fold at the highest dose), in line with the expected action of the drug on cholesterol transporters; Triglycerides and ApoB levels moderately increased at the higher doses, possibly due to increased delivery of free cholesterol and phospholipids to the liver, known to result in increased VLDL production

Preclinical-animal • Cardiovascular • Dyslipidemia

The Medicines Company: J.P. Morgan Healthcare Conference (The Medicines Company) - Anticipated launch in US for dyslipidemia in 2017 or beyond; Anticipated launch in Europe and Middle East for dyslipidemia in 2017 or beyond; Anticipated launch in Asia / Pacific region for dyslipidemia in 2017 or beyond

Anticipated launch Europe • Anticipated launch non-US • Anticipated launch US • Dyslipidemia

The Medicines Company: Cowen and Company Annual Health Care Conference (The Medicines Company) - “MDCO-216 Phase I clinical data”; “A single infusion of MDCO-216 modulated lipid parameters profoundly increased ABCA1 mediated cholesterol efflux and was well tolerated”; “These single dose data are consistent with the lipid profile of carriers of the ApoA1-Milano variant3 and data seen in monkeys in a previous study with MDCO-216”; “These data support further development of this agent as a disease-modifying treatment for reducing atherosclerotic disease and subsequent cardiovascular events”

P1 data • Dyslipidemia

The Medicines Company: Cowen and Company Annual Health Care Conference (The Medicines Company) - Anticipated interim data from P1/2 MILANO-PILOT trial (NCT02678923) for acute coronary syndrome in mid-2016

Anticipated P1/2 data • Dyslipidemia

The Medicines Company: Q4 2015 Earnings Call (The Medicines Company) - Anticipated enrollment completion of P1/2 MILANO-PILOT trial (NCT02678923) for acute coronary syndrome by mid-2016

Anticipated enrollment status • Dyslipidemia

The Medicines Company: Annual Report 2013 (The Medicines Company) - Anticipated completion of P1 trial for atherosclerosis by Q1 2014; Anticipated results from P1 trial for atherosclerosis by Q4 2014

Anticipated P1 data • Anticipated trial completion date • Dyslipidemia

The Medicines Company: Q2 FY 2016 Results (The Medicines Company) - Anticipated IDMC review of interim safety and efficacy analysis of P1/2 MILANO-PILOT trial (NCT02678923) in ACS in August 2016

Anticipated DSMB • Dyslipidemia

The Medicines Company: Earnings Call Transcript (The Medicines Company) - Anticipated data from P1 trial in patients with stable coronary artery disease for escalating doses of MDCO-216 versus placebo at American Heart Association meeting (Nov 15 -19, 2014)

Anticipated P1 data • Dyslipidemia

The Medicines Company: Investor & Analyst Day (The Medicines Company) - "MDCO-216 (ApoA1- Milano/POPC) Phase I clinical trial completed successfully"; "Up to 4 fold increase in ABCA1 efflux compared with baseline"; "ABCA1 efflux was maximally increased by 20 mg/kg in CAD patients"; "The ApoA1-Milano lipid phenotype of low HDL-C and raised TG was observed"; "MDCO-216 was well tolerated at all doses"

P1 data • Dyslipidemia

BioCentury newsmakers in the biotech industry (The Medicines Company) - Anticipated NDA filing for dyslipidemia beyond 2016

Anticipated NDA • Dyslipidemia