NEW YORK (Reuters Health) – Recombinant human neuregulin-1 (rhNRG-1) improves cardiac function and remodeling in patients with chronic heart failure (CHF), say researchers from the People’s Republic of China in the May 4th Journal of the American College of Cardiology.
“Neuregulin is a novel drug for heart failure with a brand new mechanism, and its efficacy and safety have been evaluated in CHF patients,” co-author Dr. Xinyan Li from Zensun Science and Technology Co. Ltd. in Shanghai told Reuters Health by email. “Different from other currently used drugs, it directly improves the structure of cardiomyocytes and reverses left ventricular remodeling.”
Dr. Li and colleagues investigated the efficacy of rhNRG-1 on cardiac pump function and remodeling in CHF patients in New York Heart Association (NYHA) functional class II or III. In a multicenter phase II trial, they randomly assigned 44 subjects to receive rhNRG-1 (either 0.3, 0.6, or 1.2 mcg/kg/day) or placebo for 10 days.
In patients taking 0.6 mcg/kg/day, an increase in left ventricular ejection fraction (LVEF) became evident on day 11. At day 30 – 20 days after treatment ended — LEVF in this group had increased by 27.11% (p=0.009). The increase was still significant at day 90 (31.99%; p=0.02).
Changes were less dramatic with 0.3 mcg/kg/day dose (11.55% at day 90, p=0.03). There was no improvement in LVEF with 1.2 mcg/kg/day or with placebo.
End-systolic and end-diastolic volumes were lowered by the 0.6- and 0.3-mcg/kg/day treatments, even after LVEF had improved. The 0.6-mcg/kg/day dose was most effective for inhibiting cardiac enlargement.
Other endpoints — 6-minute walk distance, quality of life, and NYHA functional class — did not differ between the placebo and rhNRG-1 groups, likely as a result of the small sample number, the authors say.
Only the 1.2 mcg/kg/day group had an increase in adverse events compared to the placebo group. Gastrointestinal disorders were most common, and there were no serious adverse events.
“Neuregulin has become a hot drug candidate for heart failure treatment considering its novel therapeutic mechanism and significant efficacy,” Dr. Li said. “rhNRG-1 may be the first novel drug which can improve the cardiac function fundamentally.”
“We have already started a phase III clinical trial in China (that) will investigate the efficacy of rhNRG-1 in reducing the death rate in heart failure patients,” Dr. Li added. “We have approval from the FDA to conduct a phase II clinical trial in the USA, and it will be set up in the near future. A phase IIa trial has already been finished in Australia.”
Five of the 11 authors have received research grants or own shared in Zensun Science and Technology Co. Ltd., which manufactures rhNRG-1.
Reference:
J Am Coll Cardiol 2010;55:1907-1914.
