Bayer unit takes heart failure gene therapy into phase 2

Bayer’s AskBio gene therapy unit has started recruiting patients into a phase 2 trial of its AB-1002 candidate for congestive heart failure (CHF), buoyed by encouraging data from a first-in-human study.

The new GenePHIT study is enrolling patients with non-ischaemic cardiomyopathy and New York Heart Association (NYHA) class III heart failure who have been medically stable for at least 4 weeks.

People with this stage of CHF will have a marked reduction in their ability to carry out exercise and will be comfortable only at rest. Up to 150 patients will be randomised in the study to receive either a single intracoronary infusion of the gene therapy, given at two dose levels, or a matched placebo.

AB-1002 delivers a gene coding for a therapeutic protein, called inhibitor-1 or I-1, which blocks the activity of protein phosphatase 1 (PP1), thought to play a role in the development of heart failure.

The primary analysis of the study will take place at 52 weeks, looking at cardiovascular death and hospitalisation rates, as well as patients’ exercise capacity, heart function, and blood oxygen levels. The subjects will also be followed up for at least three years to investigate the longer-term safety and efficacy of the gene therapy.

The start of the phase 2 trial comes after AskBio reported the first clinical data for AB-1002 (also known as NAN-101) at the American Heart Association (AHA) annual congress in November, which showed preliminary signs of efficacy, with no serious adverse events linked to the treatment.

Patients who had completed 12 months of follow-up had “clinically meaningful” improvements in left ventricular ejection fraction (LVEF), a measure of heart performance, according to the investigators.

That was accompanied by improvements in other measures, like the NYHA Functional Class (NYHA FC), Minnesota Living with Heart Failure Questionnaire (MLHFQ), cardiopulmonary exercise test (VO2 max), and 6-minute walk test (6MWT).

Approximately 26 million people worldwide are living with CHF, which occurs when the heart cannot pump blood efficiently enough to meet the body’s needs, including providing sufficient oxygen to the organs.

Bayer launched its cell and gene therapy business in 2020, shortly before it acquired AskBio for $4 billion, and is developing several candidates for disorders including Pompe disease, Parkinson’s disease, Huntington’s disease, multiple system atrophy, and limb-girdle muscular dystrophy (LGMD).

Earlier this month, it reported the first data from a clinical trial of its AB-1005 candidate for Parkinson’s, showing it was well-tolerated in a group of 11 patients 18 months after the therapy was neurosurgically delivered into the brain. Patients will be followed for up to five years for safety and efficacy in alleviating motor and non-motor symptoms of the disease.