AskBio's AB-1002 Gene Therapy Shows Promise in Heart Failure
Key Insights
AskBio's AB-1002 gene therapy demonstrates preliminary efficacy in treating congestive heart failure (search), with no serious adverse events reported in early clinical data.
The Phase 1 study (NAN-CS101) showed clinically meaningful improvements in left ventricular ejection fraction (LVEF) in a subset of patients with NYHA Class III heart failure (search).
AB-1002 delivers a gene coding for inhibitor-1 (I-1), which blocks protein phosphatase 1 (search) (PP1), a target implicated in the development of heart failure (search).
Bayer's AskBio unit has announced encouraging initial clinical data for its AB-1002 gene therapy in patients with congestive heart failure (search). The Phase 1 NAN-CS101 study, presented at the AHA annual congress, revealed preliminary signs of efficacy and a favorable safety profile for the adeno-associated virus (AAV) therapy.
Mechanism of Action
AB-1002 (NAN-101) works by delivering a gene that encodes for inhibitor-1 (I-1), a therapeutic protein. I-1 inhibits the activity of protein phosphatase 1 (search) (PP1), an enzyme implicated in the pathogenesis of heart failure (search). Elevated PP1 levels have been observed in failing hearts and are associated with impaired cardiac function and the development of cardiomyopathy.
Phase 1 Clinical Trial Results
The NAN-CS101 study involved a single intracoronary artery infusion of AB-1002 at various doses in patients with NYHA Class III heart failure (search). In Cohort 1, three out of six patients who completed 12 months of follow-up experienced clinically meaningful improvements in left ventricular ejection fraction (LVEF). Improvements were also noted in NYHA Functional Class (NYHA FC), Minnesota Living with Heart Failure Questionnaire (MLHFQ), cardiopulmonary exercise test (VO2 max), and 6-minute walk test (6MWT).
In Cohort 2, involving four evaluable patients, two showed improvements in MLHFQ and NYHA FC, and all four demonstrated clinically meaningful improvements in LVEF at 12 months compared to baseline. One patient experienced a fatal event, which was not attributed to the study treatment.
Expert Commentary
"Although current management has improved survival in CHF patients, most therapies do not treat the underlying causes, consequently the current standard of care does not reverse the trajectory of the disease to ultimate end-stage heart failure (search) and death," said lead investigator Timothy Henry of The Christ Hospital in Cincinnati. "These results show delivery of AB-1002 was well tolerated and resulted in positive efficacy outcomes in some patients with non-ischemic congestive heart failure."
Future Directions
AskBio is currently in the planning stages for a Phase 2 trial of AB-1002 to further assess its efficacy and safety in a larger cohort of patients. This next phase of clinical development will be crucial in determining the potential of AB-1002 as a novel treatment for heart failure (search).