FDA Approval for BACKBEAT Study A Major Potential Win for Orchestra BioMed and Medtronic in U.S. Pacemaker Market

Orchestra BioMed Holdings, Inc. (Nasdaq: OBIO), a leader in global life sciences, has received approval from the U.S. Food and Drug Administration (FDA) to initiate the pivotal BACKBEAT study. The study will assess the effectiveness and safety of atrioventricular interval modulation (AVIM) therapy, also known as BackBeat CNT™, for the treatment of hypertensive patients indicated for a dual-chamber cardiac pacemaker.

Orchestra BioMed partnered with Medtronic plc (NYSE: MDT) in July 2022 to develop and commercialize AVIM therapy for hypertensive pacemaker patients. Under this collaboration, Medtronic is offering crucial support for the global pivotal BACKBEAT study, which Orchestra BioMed is sponsoring. In the event of approval, Medtronic will have exclusive global rights to market AVIM-enabled pacing systems for this patient population. Orchestra BioMed will share in the revenue generated from Medtronic’s sales of these pacing systems. Medtronic has an estimated 60% market share in the $4.5 billion global pacemaker market.

BackBeat Cardiac Neuromodulation Therapy™, is a patented investigational bioelectronic treatment for hypertension. This therapy is designed to substantially, immediately, and persistently lower blood pressure by using programmable and adjustable bioelectronic technology that modulates the autonomic nervous system (ANS). BackBeat Cardiac Neuromodulation Therapy™ leverages standard rhythm management device hardware, such as a dual-chamber pacemaker, and utilizes the same implant procedure and lead positions. It is a patented bioelectronic therapy designed to achieve an immediate and substantial reduction in blood pressure through programmed pacing. Furthermore, this therapy is designed not only to lower blood pressure but also to maintain this reduction by modulating the autonomic nervous system (ANS) response through programmed variable pressure patterns. Importantly, it can work automatically without relying on patient compliance with background antihypertension medications. The adaptability of BackBeat Cardiac Neuromodulation Therapy™ allows it to be rapidly incorporated into existing treatment pathways for hypertensive patients already indicated for a pacemaker. This innovative bioelectronic therapy holds promise in revolutionizing the management of hypertension, offering potential benefits for individuals with high blood pressure.

Receiving IDE (Investigational Device Exemption) approval from the FDA is a significant milestone for Orchestra BioMed. The company plans to commence the BACKBEAT global pivotal study before the end of 2023. This study aims to support potential regulatory approval of AVIM therapy for hypertensive patients requiring a pacemaker. David Hochman, Chairman, Chief Executive Officer, and Founder of Orchestra BioMed, expressed his excitement about this innovative therapy and its potential to improve the standard of care for hypertensive pacemaker patients.

Hypertension, a leading modifiable risk factor for mortality affecting over one billion people worldwide, is the focus of this study. Despite the effectiveness of existing pharmaceutical treatments, more than half of individuals with hypertension do not meet blood pressure treatment goals. Hypertension is a common comorbidity in the pacemaker population, affecting over 70% of patients. AVIM therapy, if successful, could complement existing standards of care by reducing blood pressure and improving clinical outcomes.

The BACKBEAT pivotal study is a global, multi-center, prospective, randomized, double-blind study. It will assess the efficacy and safety of AVIM therapy in patients who have recently received a Medtronic dual-chamber cardiac pacemaker and have uncontrolled hypertension despite antihypertensive medications. The study will randomize approximately 500 patients, with half receiving AVIM therapy in addition to medical therapy and pacing, and the other half receiving only medical therapy and pacing. The primary efficacy endpoint of the study is the difference between the two groups in the change of mean 24-hour ambulatory systolic blood pressure at three months post-randomization. The primary safety endpoint is freedom from unanticipated serious adverse device effects in the treatment group at three months post-randomization. Double-blind follow-up will continue for 12 months to collect additional clinical endpoints. Enrollment in the BACKBEAT study is expected to begin in late 2023 after standard clinical trial initiation activities are completed.

The BACKBEAT study builds upon encouraging results from the MODERATO II pilot study, which demonstrated significant reductions in blood pressure in patients treated with AVIM therapy compared to control patients. The MODERATO II trial was a double-blind, randomized study involving 68 patients who had uncontrolled hypertension despite treatment with at least one antihypertensive medication. These patients also had an indication for the implantation or replacement of a dual-chamber pacemaker. The trial took place at 13 European centers. Patients in this trial were selected based on specific blood pressure criteria, which included daytime ambulatory systolic blood pressure (SBP) of ≥130 mm Hg and office SBP of ≥140 mm Hg. The primary efficacy endpoint for this trial was the difference in the change in 24-hour ambulatory SBP between the treatment and control groups. The study achieved this primary endpoint, demonstrating that 24-hour ambulatory SBP immediately decreased upon the activation of CNT and maintained its blood pressure-lowering effect through six months of follow-up. The between-group difference at 6 months was -8.1 mm Hg, with a 95% confidence interval of -14.2 to -1.9 (P=0.012).