TY - JOUR
T1 - Single Ascending-Dose Study of Selective ErbB4 Agonist JK07 in Heart Failure With Reduced Ejection Fraction
AU - Tang, W. H.Wilson
AU - Steiner, Johannes
AU - Kassi, Mahwash
AU - Wheeler, Matthew T.
AU - Spahillari, Aferdita
AU - Sweitzer, Nancy K.
AU - Grodin, Justin L.
AU - Solomon, Neal
AU - Singhal, Shalabh
AU - McEwen, Amanda M.G.
AU - Murphy, Samuel L.
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/9
Y1 - 2025/9
N2 - This first-in-human, phase 1, double-blind, placebo-controlled study evaluated the safety, tolerability, immunogenicity, pharmacokinetics, and exploratory efficacy of a selective ErbB4 agonist, JK07, in patients with heart failure with reduced ejection fraction (HFrEF). In these patients on optimal goal-directed medical therapy, JK07 was generally safe and well tolerated at dose levels up to 0.09 mg/kg. There was a trend toward increased incidence and severity of treatment-emergent adverse events observed at the highest dose of 0.27 mg/kg. Consistent with prolonged effects seen with transient exposure to neuregulin-1 in previous phase 1 investigations, improvements in left ventricular ejection fraction lasting up to 180 days after infusion were observed. These findings support continued clinical investigation of JK07 in heart failure.
AB - This first-in-human, phase 1, double-blind, placebo-controlled study evaluated the safety, tolerability, immunogenicity, pharmacokinetics, and exploratory efficacy of a selective ErbB4 agonist, JK07, in patients with heart failure with reduced ejection fraction (HFrEF). In these patients on optimal goal-directed medical therapy, JK07 was generally safe and well tolerated at dose levels up to 0.09 mg/kg. There was a trend toward increased incidence and severity of treatment-emergent adverse events observed at the highest dose of 0.27 mg/kg. Consistent with prolonged effects seen with transient exposure to neuregulin-1 in previous phase 1 investigations, improvements in left ventricular ejection fraction lasting up to 180 days after infusion were observed. These findings support continued clinical investigation of JK07 in heart failure.
KW - chronic systolic heart failure
KW - left ventricular ejection fraction
KW - neuregulin
UR - https://www.scopus.com/pages/publications/105011845927
UR - https://www.scopus.com/pages/publications/105011845927#tab=citedBy
U2 - 10.1016/j.jacbts.2025.101352
DO - 10.1016/j.jacbts.2025.101352
M3 - Article
AN - SCOPUS:105011845927
SN - 2452-302X
VL - 10
JO - JACC: Basic to Translational Science
JF - JACC: Basic to Translational Science
IS - 9
M1 - 101352
ER -