TX45 improves heart function, blood flow in PH-HFpEF
Tectonic: Findings support design, patient population for Phase 2 APEX study
A single dose of the investigational therapy TX45 improved heart function and blood flow, or hemodynamics, in people with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF), according to interim results from a Phase 1b clinical trial.
The part of the study involving PH-HFpEF patients is completely enrolled. Developer Tectonic Therapeutic said it will start enrolling participants with pulmonary hypertension and heart failure with reduced ejection fraction (PH-HFrEF) this month, with data expected later this year. The company believes the positive findings support the design and patient population for the ongoing Phase 2 APEX trial (NCT06616974), which will further test the potential benefits of TX45 in up to 180 adults with PH-HFpEF, ages 18-80.
APEX recently began recruiting, after U.S. regulators cleared the trial last summer. It’s enrolling participants at a site in Moldova, with dozens of other sites expected to open in the U.S., Europe, Australia, and New Zealand.
“We believe these Phase 1b interim data accelerate momentum of our TX45 clinical program as our ongoing Phase 2 APEX trial is designed to enroll a similar patient population and evaluate the same endpoints,” Alise Reicin, MD, president and CEO of Tectonic, said in a company press release. “These data strengthen our confidence in advancing TX45 for the many patients with PH-HFpEF who face high mortality and have no currently approved treatments.”
Pulmonary hypertension (PH) is marked by elevated pressure in the blood vessels that carry blood from the heart to the lungs, or the pulmonary arteries. PH-HFpEF is a type of PH caused by disease in the left side of the heart, or Group 2 PH per the World Health Organization’s classification system.
In PH-HFpEF, the heart’s left ventricle is still able to contract and pump blood out to the body at a normal rate, but it can’t fill up properly with blood between heartbeats. This leads to increased pressure in the heart that backs up toward the lungs and causes PH. Eventually, this puts too much strain on the right side of the heart, which may start to fail.
There are no specific medications approved for this form of PH. Therapies approved for other types of PH have not proven effective in PH-HFpEF.
What is TX45?
TX45 contains a version of relaxin, a naturally occurring hormone that helps blood vessels relax and widen, that’s attached to an Fc-fusion protein that allows it to last longer in the bloodstream. This should help lower blood pressure, thereby easing the symptoms of PH-HFpEF.
The Phase 1B trial, which began enrolling last spring, is designed to assess TX45 in people with Group 2 PH, including PH-HFpEF (Part A) and PH-HFrEF (Part B), where the left ventricle is too weak to pump blood effectively.
Heart function and hemodynamics are being measured before and for eight hours after a dose of TX45 (0.3 mg/kg, 1 mg.kg, or 3 mg/kg) via infusion into the bloodstream. Participants are then followed for 45 days as a safety follow-up.
The recently announced results covered data from 16 of 19 PH-HFpEF patients enrolled in Part A. Nine of the patients had combined pre- and post-capillary pulmonary hypertension (CpcPH), a more severe disease presentation where there’s elevated pressure in both the pulmonary arteries and the pulmonary veins that carry blood from the lungs to the left side of the heart.
Improvements in left heart function were observed after the treatent, including a 17.9% reduction in pulmonary capillary wedge pressure, a measure of pressure in the left side of the heart, and a 17.4% increase in cardiac output, or the amount of blood the heart pumps out.
Among those with CpcPH, pulmonary vascular resistance (PVR) improved by 32%. PVR is a measure of how difficult it is for the heart to push blood through the pulmonary arteries.
A range of other hemodynamic measures indicated improvements in heart function and blood flow across the entire study group and the CpcPH subgroup. These hemodynamic outcome measures are known to be linked to clinical outcomes such as exercise capacity in people with PH, the company indicated.
TX45 was well tolerated with no serious or severe adverse events.
Marcella K. Ruddy, MD, chief medical officer of Tectonic, said the company is “particularly encouraged by the striking results in CpcPH patients.” “This finding suggests that these patients, who have more severe disease, may have the greatest benefit from a relaxin therapeutic. These data support our planned enrichment of CpcPH patients in our Phase 2 APEX trial.”
In APEX, participants will be randomly assigned to receive TX45 (300 mg) once every two weeks, TX45 once a month, or a single placebo dose for about six months.
Based on findings from a Phase 1a study (ACTRN12623001054606) in healthy volunteers, the treatment will be given via injections under the skin, or subcutaneously. The main goals are to assess safety and the effects of TX45 on PVR. Top-line results are expected in 2026.
About the Author
