FDA Approves Pivotal Study of Orchestra Biomed’s BackBeat CNT

Orchestra BioMed Holdings Inc. has received U.S. Food and Drug Administration (FDA) investigational device exemption approval to begin its global BACKBEAT study, evaluating the efficacy and safety of atrioventricular interval modulation (AVIM) therapy (a.k.a., BackBeat CNT) in treating hypertensive patients requiring a dual-chamber cardiac pacemaker.
 
Orchestra BioMed and Medtronic plc formed a strategic collaboration last summer to develop and commercialize AVIM therapy for hypertensive pacemaker patients. Under the collaboration, Medtronic is providing Orchestra BioMed with development, clinical, and regulatory support for the BACKBEAT (BradycArdia paCemaKer with atrioventricular interval modulation for Blood prEssure treAtmenT) global pivotal study, which Orchestra BioMed is sponsoring. If approved, Medtronic will have exclusive global rights to commercialize AVIM-enabled pacing systems for this target population. Orchestra BioMed will share in the revenues generated from Medtronic sales of the AVIM-enabled pacing systems.
 
“We are thrilled to receive IDE approval from the FDA and move forward with plans to initiate the BACKBEAT global pivotal study, which is designed to support potential future regulatory review and potential approval of AVIM therapy for hypertensive patients indicated for a pacemaker. Achieving this milestone a little over a year after starting our strategic collaboration with Medtronic is a significant accomplishment for our company,” Orchestra Biomed Founder/Chairman/CEO David Hochman said. “We believe this therapy has the potential to substantially improve the standard of care for hypertensive pacemaker patients and we look forward to initiating the study before the end of 2023.”

The BACKBEAT study IDE was supported by encouraging results from MODERATO II, a prospective, multi-center, randomized, double-blind, pilot study of pacemaker patients with persistent HTN. MODERATO II showed that patients treated with AVIM therapy experienced net reductions of 8.1 mmHg in 24-hour aSBP and 12.3 mmHg in office systolic blood pressure (oSBP) at six months when compared to control patients.
 
“Hypertension is the world’s leading modifiable risk for death and affects over 1 billion people worldwide. While existing pharmaceutical treatments can be effective, more than half of individuals with hypertension do not meet blood pressure treatment goals. A device-based treatment like AVIM therapy has the potential to complement existing standards of care and reduce blood pressure to improve clinical outcome,” stated David Kandzari, M.D., chief of the Piedmont Heart Institute and chief scientific officer for Piedmont Healthcare (Atlanta) and co-principal investigator for the BACKBEAT trial.

BACKBEAT is a global, multi-center, prospective, randomized, double-blind study investigating the efficacy and safety of AVIM therapy in patients who recently underwent a Medtronic dual-chamber cardiac pacemaker implant and have uncontrolled hypertension (HTN) despite the use of antihypertensive medications. The study will randomize approximately 500 patients 1:1 to AVIM along with continued medical therapy and pacing (treatment) or continued medical therapy and pacing alone (control). The study’s primary efficacy endpoint is the between group difference in the change of mean 24-hour ambulatory systolic blood pressure (aSBP) at three months post randomization. The primary safety endpoint is freedom from unanticipated serious adverse device effects in the treatment arm at three months post-randomization. Double-blind follow up will continue through 12 months to enable collection of additional clinical endpoints. The company plans to begin enrollment in the BACKBEAT study before the year’s end, upon completion of standard clinical trial initiation activities, including clinical center Institutional Review Board approvals.
 
“Hypertension is the most common comorbidity in the pacemaker population, affecting more than 70% of patients,” noted Andrea Russo, M.D., academic chief, Division of Cardiology, director of Cardiac Electrophysiology and Arrhythmia Services, Cooper University Hospital, and co-principal BACKBEAT study investigator. “Patients who have pacemakers are generally older and at higher risk for major cardiovascular events. AVIM therapy represents a potentially transformative hypertension treatment for these patients since it can be administered using the same pacemaker they already need and managed by the same physicians already caring for them. We are excited to participate in the BACKBEAT study, which has been thoughtfully designed to evaluate the safety and efficacy of this therapy.”
 
HTN is characterized by elevated blood pressure, which increases the force of blood pushing against blood vessels, requiring the heart to work harder and consume more oxygen. HTN accelerates the progression of atherosclerosis and leads to increased risk of major cardiac events like heart attack, heart failure, kidney disease and other end organ damage. HTN is the leading global risk factor for death, affecting an estimated 1.28 billion adults worldwide. In the United States, 122 million adults, or approximately 47% of all adults, are estimated to have HTN. While many patients do not notice high blood pressure, cardiovascular risk doubles for every 10 mmHg increase in systolic blood pressure and the mortality rate doubles with an increase of 20 mmHg in systolic blood pressure.
 
It is estimated that more than 70% of the approximately 1.1 million people globally who are implanted with cardiac pacemakers each year are also diagnosed with HTN. Based on updated ACC/AHA guidelines, an even higher percentage (approximately 80%) of U.S. patients that are indicated for the implant of a pacemaker have HTN. Pacemaker patients tend to be elderly and are more likely to suffer from co-morbidities such as atherosclerosis, hyperlipidemia, diabetes mellitus and chronic kidney disease, and harder to treat effectively with medical therapy for many reasons including co-morbidities and a high prevalence of isolated systolic HTN.
 
AVIM therapy, also known as BackBeat CNT, is an investigational therapy compatible with standard dual-chamber pacemakers designed to substantially and persistently lower blood pressure. It has been evaluated in pilot studies in patients with hypertension who are also indicated for a pacemaker. MODERATO II, a double-blind, randomized pilot study, showed that patients treated with AVIM therapy experienced net reductions of 8.1 mmHg in 24-hour aSBP and 12.3 mmHg in office systolic blood pressure (oSBP) at six months when compared to control patients. The planned global pivotal BACKBEAT study will further evaluate the safety and efficacy of AVIM therapy in lowering blood pressure in a similar target population of patients who have been indicated for, and recently implanted with, a dual-chamber cardiac pacemaker.
 
Orchestra BioMed is a biomedical innovation company accelerating high-impact technologies to patients through partnerships with medical device companies. Orchestra BioMed’s partnership-enabled business model focuses on forging strategic collaborations with medical device companies to successfully commercialize the products it develops. Orchestra BioMed’s flagship product candidates include AVIM therapy for treating hypertension, and Virtue Sirolimus AngioInfusion Balloon (SAB) for treating atherosclerotic coronary artery disease. In addition to its partnership with Medtronic, Orchestra BioMed also has a strategic collaboration with Terumo to develop and commercialize Virtue SAB. Orchestra BioMed has additional product candidates and plans to potentially expand its product pipeline through acquisitions, strategic collaborations, licensing, and organic development.