Phase 2 trial of TX45 in PH-HFpEF patients completes enrollment
Top-line results from APEX study expected in early 2027
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Enrollment is complete in the Phase 2 APEX trial of TX45, Tectonic Therapeutic‘s experimental drug for pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF), the company reports.
“Reaching full enrollment in our APEX Phase 2 clinical trial represents a critical milestone for our TX45 clinical development program and brings us one step closer to potentially delivering a much-needed therapeutic option to patients suffering from PH-HFpEF,” Alise Reicin, MD, Tectonic’s president and CEO, said in a company press release. “With the trial now fully enrolled, we look forward to the upcoming topline results for APEX, expected in [early 2027], which will help further characterize the therapeutic profile of our candidate and guide our strategy moving forward.”
TX45 may help relieve strain on the heart
Pulmonary hypertension, or PH, is a condition characterized by high blood pressure in the vessels that supply the lungs, called the pulmonary arteries. This forces the heart to work harder to pump blood throughout the body. As a result, cells and tissues may not receive enough oxygen.
A variety of underlying causes can lead to PH, including left-sided heart disease. In HFpEF, the main pumping chamber of the heart, the left ventricle, contracts correctly during heartbeats. However, between heartbeats, the ventricle doesn’t entirely relax, causing problems as it refills with blood.
Ultimately, it may increase pressure in the heart that can back up toward the lungs, increasing pulmonary blood pressure.
TX45 is an experimental therapy that may help reduce this pressure and relieve strain on the heart. It contains a long-lasting formulation of relaxin, a hormone that helps widen blood vessels and increase heart output. Early Phase 1b trial results showed that a single dose of the medication improved heart function for participants with PH-HFpEF.
Tectonic designed the Phase 2 APEX trial (NCT06616974) to follow up on these findings and investigate longer-term dosing. PH-HFpEF participants will receive subcutaneous (under-the-skin) doses of TX45 or a placebo. There will be three treatment groups — one that only receives TX45, one that only receives the placebo, and one that alternates between the two (corresponding with a TX45 dose every four weeks).
The strong momentum we experienced during enrollment underscores the significant unmet medical need in PH-HFpEF, especially in patients with CpcPH.
Treatment will continue for 24 weeks, or nearly six months, while participants undergo monitoring for safety and efficacy. Measurements will include pulmonary vascular resistance (PVR), which quantifies how hard the heart needs to pump to deliver blood through the lungs.
Investigators are particularly interested in the effects of TX45 for people with combined pre- and post-capillary pulmonary hypertension (CpcPH). This is a severe form of PH-HFpEF that affects both the pulmonary arteries and the pulmonary veins that carry blood from the lungs to the left side of the heart.
One of the main goals of APEX is to measure changes in PVR in the CpcPH subgroup. Other primary outcomes include safety and results of physical exams. Monitoring will also include other metrics of blood pressure in the lungs, exercise capacity, biological markers of heart disease, and clinical rating scales.
With enrollment now complete, the study includes 191 PH-HFpEF participants from 14 countries. Of these, 72% have CpcPH and a PVR above a preset threshold, meeting Tectonic’s goal to focus on this subgroup.
“We are deeply grateful to the clinical investigators, study coordinators, and, most importantly, the patients and their families whose participation makes this vital research possible,” Reicin said. “The strong momentum we experienced during enrollment underscores the significant unmet medical need in PH-HFpEF, especially in patients with CpcPH.”
Tectonic is also sponsoring the Phase 2 ALPINE trial (NCT07473700) testing TX45 as a therapy for PH with interstitial lung disease, another form of the condition.
