Patients With Congestive Heart Failure Show Clinically Meaningful Improvements After Gene Therapy

Patients with congestive heart failure (CGF) treated with AB-1002 (AskBio; NAN-101) gene therapy showed clinically meaningful improvements in multiple functional outcomes in a phase 1/2 clinical trial (NCT04179643).

Data from the trial were presented at the American Heart Association’s (AHA) Scientific Sessions 2023, held November 10-13 in Philadelphia, Pennsylvania.

"We believe these encouraging early results in patients with advanced heart failure are important for the congestive heart failure community, as they bring hope to a sub-population where treatment options are needed," Litsa G. Kranias, PhD, Hanna Chair of Cardiology, University of Cincinnati and US Coordinator, Cure-PLaN, said in a statement. "Seeing the potential of gene therapy being explored in heart failure is a key step forward in one day potentially changing the direction of this devastating disease, which is a leading cause of morbidity and mortality in westernized countries."

Investigators found that 3 of 6 patients in cohort 1, those that completed 12-month follow-up, showed clinically meaningful improvements in left ventricular ejection fraction (LVEF), NYHA Functional Class (NYHA FC), Minnesota Living with Heart Failure Questionnaire (MLHFQ), cardiopulmonary exercise test (VO2 max), and 6-minute walk test (6MWT) compared to baseline. The remaining 3 patients are still within 3 months of treatment and not yet evaluable.

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In cohort 2, 2 of 5 patients, showed clinically meaningful improvements in MLHFQ and NYHA FC and all 4 evaluable patients showed clinically meaningful improvements in LVEF at 12 months, compared with baseline. One patient was not evaluable due to a fatal, unrelated-to-treatment, serious adverse event (AE). No serious or treatment emergent AEs were deemed related to AB-1002 gene therapy.

"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 and death. 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,” principal investigator Timothy D. Henry, MD, MSCAI, Steering Committee Member, AskBio and Lindner Family Distinguished Chair in Clinical Research and Medical Director, Carl and Edyth Lindner Center for Research, The Christ Hospital, added to the statement.

AB-1002 is a cardiotropic adeno-associated virus(AAV) vector gene therapy, administered via injection to the heart, designed to promote increased production of a therapeutic protein inhibitor 1 and block protein phosphatase 1, which has been linked to CHF.

"At AskBio we are committed to our mission of transforming gene therapies from idea to impact. These results further validate that the AAV2i8 vector capsid is highly cardiotropic when injected through intracoronary means at relatively low doses. This is encouraging as it shows the exciting potential for gene therapy to reduce the considerable burden of congestive heart failure in a sub-population of heart failure patients where the current prognosis is particularly poor,” Canwen Jiang, MD, PhD, chief development officer and chief medical officer, AskBio, added.

REFERENCE
AskBio presents preliminary data from phase 1 trial of gene therapy for congestive heart failure (CHF) at the 2023 American Heart Association Scientific Sessions. News release. AskBio. November 12, 2023. https://www.prnewswire.com/news-releases/askbio-presents-preliminary-data-from-phase-1-trial-of-gene-therapy-for-congestive-heart-failure-chf-at-the-2023-american-heart-association-scientific-sessions-301985319.html