Author + information
- Daniel J. Lenihan,
- Sarah Anderson,
- Carrie Geisberg,
- Anthony Caggiano,
- Andrew Eisen,
- Evan Brittain,
- James A.S. Muldowney III,
- Lisa Mendes and
- Douglas Sawyer
Glial Growth Factor 2 (GGF2) is a neuregulin peptide critical for cardiac function. GGF2 enhances myocardial function and repair in animal models of cardiac injury. A first-in-human, double-blind, placebo-controlled, single escalating dose study was conducted to begin examining safety and tolerability of GGF2 in patients with systolic heart failure (HF).
After informed consent, 40 patients with symptomatic HF were randomized (4:2) to GGF2 or placebo in 7 ascending dose cohorts from 0.007 to 1.5 mg/kg. Patients were observed in hospital for 30 hours, then evaluated for adverse events (AEs) at 1, 2, 4, 12, and 24 weeks after infusion. AEs were graded using the Combined Toxicity Criteria.
There were no notable effects of treatment on hematologic or electrical parameters and no AEs leading to withdrawal. Treatment Emergent AEs are shown in Table 1. A dose-limiting toxicity meeting Hy's Law criteria (ALT, AST, bilirubin) and one case of superficial uroepithelial carcinoma occurred in the seventh cohort (1.5 mg/kg).
A single dose of GGF2 in patients with HF was generally well tolerated up to 0.75 mg/kg. Higher doses may be associated with reversible hepatotoxic events. Further studies are needed to assess safety and tolerability GGF2 therapy in symptomatic HF.
Poster Sessions, Expo North
Sunday, March 10, 2013, 9:45 a.m.-10:30 a.m.
Session Title: Heart Failure: Pharmacologic Therapy
Abstract Category: 17. Heart Failure: Therapy
Presentation Number: 1223-308
- 2013 American College of Cardiology Foundation