Clinical Research
A Phase I, Single Ascending Dose Study of Cimaglermin Alfa (Neuregulin 1β3) in Patients With Systolic Dysfunction and Heart Failure

Presented in part at the American College of Cardiology Annual Meeting, 2015, San Diego, California.
https://doi.org/10.1016/j.jacbts.2016.09.005Get rights and content
Under a Creative Commons license
open access

Highlights

  • Cimaglermin is a recombinant neuregulin that appears to be important for essential cardiac repair processes.

  • Forty patients with significant left ventricular dysfunction and heart failure were randomized in a phase 1 double blind, placebo controlled, single ascending dose study to examine safety and tolerability.

  • An infusion of cimaglermin was generally tolerated except for transient nausea and headache.

  • A dose-limiting toxicity of transient elevated liver transaminases and bilirubin was observed at the highest planned dose.

  • There was a sustained improvement in left ventricular ejection fraction over 3 months at higher doses tested compared to lower doses or placebo.

Summary

A first-in-human, phase 1, double blind, placebo-controlled, single ascending dose study examined the safety, tolerability, and exploratory efficacy of intravenous infusion of a recombinant growth factor, cimaglermin alfa, in patients with heart failure and left ventricular systolic dysfunction (LVSD). In these patients on optimal guideline-directed medical therapy, cimaglermin treatment was generally tolerated except for transient nausea and headache and a dose-limiting toxicity was noted at the highest planned dose. There was a dose-dependent improvement in left ventricular ejection fraction lasting 90 days following infusion. Thus, cimaglermin is a potential therapy to enhance cardiac function in LVSD and warrants further investigation.

Key Words

cardiac repair
growth factor
neuregulin
systolic dysfunction

Abbreviations and Acronyms

AE
adverse event
AUC
area under the curve
DLT
dose-limiting toxicity
GGF
glial growth factor
HF
heart failure
LVEF
left ventricular ejection fraction
LVSD
left ventricular systolic dysfunction
NRG
neuregulin
NYHA
New York Heart Association functional class
TEAE
treatment-emergent adverse event

Cited by (0)

This study was funded by Acorda Therapeutics, Inc., Ardsley, New York. Drs. Lenihan and Sawyer are consultants with and have received research funding from Acorda Therapeutics, Inc. Dr. Lenihan has also received support from Takeda, Roche, Bristol-Myers Squibb, Prothena, and Amgen. Dr. Brittain has received funding from Gilead Sciences. Dr. Zolty was an employee of Acorda Therapeutics, Inc., at the time of the study and is now a paid consultant to Acorda Therapeutics, Inc. Ms. Iaci and Drs. Caggiano, Zhao, and Eisen are employed by and own stock in Acorda Therapeutics, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.