MEDI6012 / AstraZeneca - LARVOL DELTA

Cardiometabolic Risk Factors and Non-Culprit Plaque Characteristics in Patients With STEMI in REAL-TIMI 63B (AHA 2023) - "However, NCPV and associations with clinical characteristics in patients presenting with a first acute STEMI are not well described. The REAL-TIMI 63B trial randomized 593 patients with no prior MI presenting with acute STEMI to intravenous recombinant human lecithin-cholesterol acyltransferase (MEDI6012) or placebo; a subset were to undergo CCTA 48-72h after STEMI... Among patients with no prior MI undergoing primary PCI for STEMI, we found that most patients had NCPV and LAPV outside the culprit lesion. Male sex and markers of cardiometabolic disease including higher BMI and diabetes were associated with a greater burden of NCPV. These observations underscore the need for intensive medical therapies that may stabilize vulnerable plaque in patients presenting with acute myocardial infarction."

Clinical • Cardiovascular • Diabetes • Metabolic Disorders • Myocardial Infarction • Obesity

MEDI6012: Recombinant Human Lecithin Cholesterol Acyltransferase, High-Density Lipoprotein, and Low-Density Lipoprotein Receptor-Mediated Reverse Cholesterol Transport. (PubMed, J Am Heart Assoc) - P2a | "These findings are supportive of enhanced reverse cholesterol transport and a functional high-density lipoprotein phenotype. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02601560."

Journal • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Heart Failure • APOA1 • APOB

Randomized, Placebo-Controlled Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Lecithin Cholesterol Acyltransferase in Acute ST-Segment-Elevation Myocardial Infarction: Results of REAL-TIMI 63B. (PubMed, Circulation) - P2b | "Administration of MEDI6012 in patients with acute ST-segment-elevation myocardial infarction did not result in a significant reduction in infarct size or noncalcified plaque volume at 12 weeks. MEDI6012 was well tolerated with no excess in overall serious adverse events."

Journal • P2b data • Cardiovascular • Myocardial Infarction

[VIRTUAL] CARDIOPROTECTION AND PLAQUE REGRESSION WITH MEDI6012 IN ACUTE ST ELEVATION MYOCARDIAL INFARCTION - PRIMARY RESULTS OF THE REAL-TIMI 63B RANDOMIZED CLINICAL TRIAL (ACC 2021) - P2b | "The results of the REAL-TIMI 63B trial will provide an initial assessment of the efficacy and safety of recombinant human LCAT for reduction of IS and NCCPV and is expected to inform future development of MEDI6012."

Clinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Myocardial Infarction

Intravenous ACP-501 for Familial LCAT Deficiency (rhLCAT) (clinicaltrials.gov) - P; N=1; Completed; Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Clinical • New trial

Recombinant human Lecithin-Cholesterol acyltransferase in patients with atherosclerosis: Phase 2a primary results and phase 2b design. (PubMed, Eur Heart J Cardiovasc Pharmacother) - "Multiple ascending doses of MEDI6012 were safe and well tolerated and significantly increased HDL-C, HDL-CE and CE in a dose-related manner. These data support the ongoing Phase 2 b program investigating MEDI6012 in ST-elevation MI."

Clinical • Journal • P2a data • P2b data • Atherosclerosis • Cardiovascular • Dyslipidemia

Study to Evaluate the Effects of MEDI6012 on Apolipoprotein B100 Metabolism (clinicaltrials.gov) - P2; N=7; Terminated; Sponsor: Columbia University; Recruiting ➔ Terminated; Trial primary completion date: Oct 2019 ➔ May 2020; Early termination due to COVID-19

Clinical • Trial primary completion date • Trial termination • Atherosclerosis • Cardiovascular • Dyslipidemia • APOB

REAL-TIMI 63B: A Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction (clinicaltrials.gov) - P2b; N=595; Completed; Sponsor: MedImmune LLC; Active, not recruiting ➔ Completed

Clinical • Trial completion • Cardiovascular • Myocardial Infarction

REAL-TIMI 63B: A Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction (clinicaltrials.gov) - P2b; N=594; Active, not recruiting; Sponsor: MedImmune LLC; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Cardiovascular • Myocardial Infarction

AlphaCore granted orphan drug designation for ACP-501 (rhLCAT) by European Medicines Agency (Business Wire) - AlphaCore announced it has received orphan drug designation from the EMA for ACP-501 for the treatment of familial LCAT deficiency; This EMA designation follows an earlier FLD orphan drug designation granted by the FDA

European regulatory • Dyslipidemia

REAL-TIMI 63B: A Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction (clinicaltrials.gov) - P2b; N=540; Recruiting; Sponsor: MedImmune LLC; Active, not recruiting ➔ Recruiting; Trial completion date: Jul 2020 ➔ Nov 2020; Trial primary completion date: Jul 2020 ➔ Nov 2020

Clinical • Enrollment open • Trial completion date • Trial primary completion date • Acute Coronary Syndrome • Cardiovascular • Myocardial Infarction

AlphaCore reports positive phase 1 results for ACP-501 (rhLCAT) in patients with stable atherosclerosis (Business Wire) - P1, N=16; NCT01554800; AlphaCore announced that results from the company’s P1 clinical trial have met the primary endpoint by demonstrating the safety & tolerability of the drug ACP-501 (recombinant human LCAT); ACP-501 also met the secondary endpoints by rapidly & substantially elevating HDL cholesterol; The elevation of HDL cholesterol was due entirely to an increased formation of cholesteryl esters

P1 data • Dyslipidemia

Safety and Tolerability of ACP-501, a Recombinant Human Lecithin:Cholesterol Acyltransferase, in a Phase 1 Single-Dose Escalation Study. (PubMed) - Circ Res - "ACP-501 has an acceptable safety profile after a single IV infusion. Lipid and lipoprotein changes indicate that rhLCAT favorably alters HDL metabolism and support rhLCAT use in future clinical trials in CHD and FLD patients. ClinicalTrials.gov Identifier: NCT01554800."

Journal • Acute Coronary Syndrome • Biosimilar • Heart Failure

Effect of ACP-501 on safety, tolerability, pharmacokinetics and pharmacodynamics in subjects with coronary artery disease (clinicaltrials.gov) - P1, N=16; Sponsor: AlphaCore Pharma; Recruiting -> Completed.

Trial completion • Dyslipidemia

AstraZeneca: Q3 FY 2016 Results (AstraZeneca) - Anticipated top-line results from P2a (NCT02601560) trial in adults with stable CAD and low HDL in H2 2016

Anticipated P2a data • Dyslipidemia

REAL-TIMI 63B: A Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction (clinicaltrials.gov) - P2b; N=540; Active, not recruiting; Sponsor: MedImmune LLC; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Acute Coronary Syndrome • Cardiovascular • Myocardial Infarction

REAL-TIMI 63B: A Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction (clinicaltrials.gov) - P2b; N=540; Recruiting; Sponsor: MedImmune LLC; N=414 ➔ 540; Trial completion date: Mar 2020 ➔ Jul 2020; Trial primary completion date: Mar 2020 ➔ Jul 2020

Clinical • Enrollment change • Trial completion date • Trial primary completion date

Study to Evaluate the Effects of MEDI6012 on Apolipoprotein B100 Metabolism (clinicaltrials.gov) - P2; N=8; Recruiting; Sponsor: Columbia University; Not yet recruiting ➔ Recruiting; Trial primary completion date: Jun 2019 ➔ Oct 2019

Clinical • Enrollment open • Trial primary completion date