Clinical Data Show Positive Blood Pressure, Hemodynamic Effects of AVIM Therapy

A study published in the Journal of the American College of Cardiology: Clinical Electrophysiology shows favorable hemodynamic effects of Orchestra BioMed Holdings Inc.’s AVIM therapy in patients with pacemakers who suffer from uncontrolled hypertension.

AVIM therapy is currently being evaluated in the BACKBEAT global pivotal study, which Orchestra BioMed is conducting with Medtronic, to support potential future global regulatory approvals and commercialization of AVIM therapy-enabled devices.

The publication, “Pressure-Volume Analysis Demonstrates Short- and Long-Term Hemodynamic Effects of Atrioventricular Interval Modulation Therapy in Hypertension,” reports findings from an invasive PV loop analysis in 16 hypertensive pacemaker-indicated subjects, as well as noninvasive PV loop analysis from a subgroup of subjects (n=32) from the MODERATO II study receiving chronically administered AVIM therapy. The analyses demonstrated that AVIM therapy reduced systolic blood pressure (SBP) acutely by decreasing cardiac preload and effective arterial elastance unrelated to pacing lead location, while also improving left ventricular (LV) end-diastolic and end-systolic volumes. Chronically administered AVIM therapy demonstrated sustained reductions in SBP and end-diastolic volume, indicative of favorable reverse LV remodeling. Results also demonstrated consistently favorable hemodynamic effects using traditional right ventricular (RV) and conduction system pacing (CSP) lead placements.

“Pressure-volume loop analysis is regarded as the gold standard for assessing systolic and diastolic function as well as reverse remodeling. These results provide powerful insights on the impact of AVIM therapy to both decrease blood pressure and favorably impact ventricular end-diastolic volume without compromising cardiac output or increasing workload,” said Daniel Burkhoff, M.D., Ph.D., director of Heart Failure, Hemodynamics, and MCS Research, Cardiovascular Research Foundation, and a manuscript author. “Notably, these favorable effects were observed consistently and with different pacing lead locations, demonstrating the versatility of AVIM therapy. Publication of these data in a peer-reviewed journal such as JACC: Clinical Electrophysiology provides further validation from the clinical community reinforcing the therapeutic rationale behind AVIM therapy and further highlighting its potential to deliver differentiated clinical benefit for patients with uncontrolled hypertension.”

Key findings include:

• Significantly reduced (p<0.05) systolic blood pressure (“SBP”): average decreases of 17.1 mmHg (AVIM via RV pacing) and 19.2 mmHg (AVIM via CSP ), compared to 1.7 mmHg with standard dual-chamber pacing.
• Improved left ventricular hemodynamics with both RV pacing and CSP, respectively, compared to standard pacing:
  • End-diastolic volume significantly decreased by 12.6 mL and 18.6 mL compared to 1.4 mL
  • End-systolic volume significantly decreased by 11.0 mL and 14.1 mL compared to an increase of 1.8 mL
  • End-diastolic pressure significantly decreased by 2.1mmHg and 3.9 mmHg, compared to an increase of 0.3 mmHg
• Significantly reduced (p<0.05) cardiac workload: Stroke work decreased by 1,596 mL (RV) and 1,870 mL (CSP), compared to 42mL (standard pacing), with minimal impact on stroke volume.
• Significantly reduced total peripheral resistance (“TPR”, measured by Ea):
  • Effective arterial elastance (“Ea”) decreased by 0.23 mmHg/mL (RV) and 0.31 mmHg/mL (CSP), compared to an increase of 0.04 mmHg/mL (standard pacing).

“The publication of the PV loop data in JACC: Clinical Electrophysiology marks another important milestone showcasing AVIM therapy’s potential ability to significantly reduce blood pressure and favorably impact cardiac function in hypertensive patients with increased cardiovascular risk,” stated Yuval Mika, Ph.D., executive vice president, Bioelectronic Therapies, at Orchestra BioMed. “The consistent reduction seen in cardiac preload, as well as cardiac afterload with both CSP and RV lead placements in these pilot studies demonstrates that AVIM therapy’s mechanism of action works regardless of lead location. Furthermore, acute and chronic PV loop results indicate AVIM therapy’s potential to induce positive reverse remodeling of ventricular hypertrophy, highlighting potential to prevent or even treat heart failure. We continue to believe that AVIM therapy has the potential to reshape the standard of care for higher risk patients with uncontrolled hypertension in the pacemaker population and beyond.”

AVIM therapy 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 also have 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 ambulatory systolic blood pressure (aSBP) and 12.3 mmHg in office systolic blood pressure (oSBP) at six months when compared to control patients. In addition to reducing blood pressure, clinical results using AVIM therapy demonstrate improvements in cardiac function and hemodynamics. The BACKBEAT (BradycArdia paCemaKer with atrioventricular interval modulation for Blood prEssure treAtmenT) global pivotal study will evaluate the safety and efficacy of AVIM therapy in lowering blood pressure in patients who have systolic blood pressure above target despite anti-hypertensive medication and who are indicated for or have recently received a dual-chamber cardiac pacemaker. AVIM therapy has been granted Breakthrough Device Designation by the U.S. Food and Drug Administration for treating uncontrolled hypertension in patients with increased cardiovascular risk.

Orchestra BioMed is a biomedical company accelerating high-impact technologies to patients through risk-reward sharing partnerships with medical device companies. Orchestra BioMed’s partnership-enabled business model focuses on forging strategic collaborations with medical device companies to drive successful global product commercialization. Orchestra BioMed’s lead product candidate is atrioventricular interval modulation (AVIM) therapy (also known as BackBeat Cardiac Neuromodulation Therapy (CNT)) for treating hypertension. Orchestra BioMed is also developing the Virtue Sirolimus AngioInfusion Balloon (SAB) for treating atherosclerotic artery disease. Orchestra BioMed has a strategic collaboration with Medtronic for developing and commercializing AVIM therapy for treating hypertension in patients with pacemakers, and a strategic partnership with Terumo to develop and commercialize Virtue SAB for treating artery disease.