Tectonic Therapeutic's TX45, a long-acting Fc-relaxin fusion protein, has shown positive interim data from its Phase 1b clinical trial, offering hope for patients with Group 2 Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction (PH-HFpEF). The trial's results, announced January 30, 2025, indicate that a single intravenous dose of TX45 led to meaningful improvements in both left ventricular function and pulmonary hemodynamics. These findings could represent a significant advancement in treating a condition with limited approved therapies and high mortality rates.
The Phase 1b trial enrolled 19 patients with PH-HFpEF, with the interim analysis focusing on 16 patients. The study evaluated hemodynamic endpoints similar to those in Tectonic's ongoing APEX Phase 2 clinical trial, which is expected to yield topline results in 2026.
Hemodynamic Improvements
In the overall study population, TX45 achieved a 17.9% reduction in pulmonary capillary wedge pressure (PCWP) [95% CI, -9.8% to -26.1%], a key endpoint correlating with exercise capacity, morbidity, and mortality in heart failure patients. Notably, in the subpopulation with combined pre- and post-capillary pulmonary hypertension (CpcPH), characterized by elevated pulmonary vascular resistance (PVR), TX45 demonstrated a greater than 30% reduction in PVR [95% CI, -28.1% to -35.9%].
"These interim results show that TX45 achieved improvements in hemodynamics which met and exceeded our prespecified objectives," said Alise Reicin, M.D., President and Chief Executive Officer of Tectonic. "We are highly encouraged that TX45 improved left ventricular function and pulmonary hemodynamics, because we believe improving both parameters is necessary to improve exercise capacity and outcomes in patients with pulmonary hypertension with HFpEF."
Safety and Tolerability
TX45 was well-tolerated in the trial, with no serious or severe adverse events, discontinuations, infusion reactions, or drug-related adverse events reported. Transient asymptomatic decreases in blood pressure were observed in the first 24 hours post-dosing.
Implications for PH-HFpEF Treatment
Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction (PH-HFpEF) is a subtype of Group 2 pulmonary hypertension that develops due to left-sided heart disease. It affects approximately 1.4 million people in the U.S., with CpcPH representing a more severe form of the disease. Currently, no medications are specifically approved for PH-HFpEF, highlighting the urgent need for effective treatments.
John Teerlink, MD, Professor of Medicine, University of California, San Francisco, commented, "These therapeutic results show remarkably consistent and meaningful improvement across multiple clinically important hemodynamic measures in this patient population. I am excited about the prospects ahead for the continued development of TX45 which appears to address the underlying pathologies of PH-HFpEF that lead to impairment of exercise capacity, poor outcomes and increased mortality."
Ongoing and Future Development
Tectonic is currently conducting the Phase 2 APEX trial (NCT06616974), a 24-week clinical trial in PH-HFpEF, with topline results expected in 2026. The Phase 1b trial also includes Part B, which will evaluate the effects of TX45 in Pulmonary Hypertension in Heart Failure with reduced Ejection Fraction (PH-HFrEF), with topline data expected in the second half of 2025. These trials aim to further define the therapeutic effects of TX45 and its potential role in treating patients with PH-HFpEF and PH-HFrEF.
