An FDA panel meeting in early December will give a hint as to whether Impulse Dynamics will become the first company to bring a heart muscle stimulator to US patients with heart failure. A positive verdict will be important to the company given its stated intention to go public next year.
Impulse’s implant, the Optimizer Smart, succeeded in its pivotal US trial, and has FDA breakthrough status. But the study was not sham controlled, and it concerned measures like exercise tolerance and quality of life; in the absence of data on harder endpoints such as survival it is possible that the panel might vote against the product.
The Optimizer Smart is a second-generation version of a first-of-its-kind device. An earlier iteration is CE marked and on sale in Europe, but it is not yet available in the US.
The Optimizer senses ventricular activity and delivers shocks to the heart that are designed to modulate the strength of heart muscle contraction. It is intended for drug-refractory patients with New York Heart Association class III heart failure – those who are not sick enough to require heart transplants or ventricular assist devices, the main device therapies for heart failure.
The device’s PMA filing is based on the results of the Fix-HF-5C trial, which compared the Optimizer plus heart failure medication against drugs alone in patients with ejection fractions between 25% and 45%. Peak VO2, a measure of exercise capacity, quality of life questionnaire scores and NYHA class – a measure of disease severity – were all significantly better in the treatment group (Impulse Dynamics aims to find its niche in heart failure, May 23, 2018).
The study involved unusual statistical considerations, its Bayesian design permitting a 30% borrowing from the earlier Fix-HF-5 trial. Fix-HF-5 failed overall, but a hypothesis-generating subgroup analysis showed significant effects with the Optimizer in patients with ejection fractions ranging from 25% to 45%, a subgroup that included roughly half of all the study subjects.
One finding with which the panel will concern itself is the significant reduction in the composite of cardiovascular death and heart failure hospitalisations, from 10.8% with drugs alone to 2.9% using the Optimizer.
A panel vote to recommend approval of the stimulator is crucial for Impulse’s long-term ambitions. The company previously told Vantage that it was planning a “disruptive, major, large-scale IPO” for 2019. Many potential investors will consider having a device on the US market a prerequisite before they part with their cash.