TX45 shows promising results in people with PH and heart failure
Therapy improves heart function, circulatory health in small clinical trial
The investigational treatment TX45 may help improve heart function and circulatory health in people with pulmonary hypertension and heart failure with reduced ejection fraction (PH‑HFrEF).
That’s according to new early clinical trial data announced by developer Tectonic Therapeutic, which tested a single intravenous (into-the-vein) dose of the therapy candidate in about a dozen patients.
The results were overall similar to findings seen in people with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF), which were reported earlier this year — meaning TX45 may work for a broader group of PH patients.
“We met the goal of this exploratory study in patients with PH‑HFrEF, which was to observe improvements in [blood flow measurements] … that were directionally similar to the positive results of our Phase 1b Part A study in PH-HFpEF,” Alise Reicin, MD, president and CEO of Tectonic, said in a company press release.
PH-HFrEF and PH-HFpEF are both forms of group 2 pulmonary hypertension, referring to elevated pressure in the blood vessels of the lungs due to issues in the left part of the heart. In PH-HFrEF, the left heart is too weak to pump properly, whereas in PH-HFpEF, the heart doesn’t fill correctly in between pumps.
TX45 is a modified version of relaxin, a naturally occurring hormone that prompts blood vessels to relax and widen. The new data come from a Phase 1 clinical trial that tested TX45 in both PH-HFrEF and PH-HFpEF.
Findings echo those seen for TX45 use in PH-HFpEF
The PH‑HFrEF arm of the study enrolled 14 patients, all of whom were given a single dose of the long-acting therapy.
The results showed that, after TX45, there was a reduction in average measurements of pulmonary capillary wedge pressure (PCWP) and an increase in average cardiac output — both of which suggest an improvement in left heart function.
Measures that reflect the amount of pressure in the lungs’ blood vessels — including pulmonary vascular resistance, total pulmonary resistance, and mean pulmonary artery pressure — generally indicated less pressure following TX45.
The researchers noted that improvements in these blood flow measures were seen even in patients with combined pre- and post-capillary pulmonary hypertension (CpcPH), which is a specific pattern of left-sided heart disease that can occur in PH-HFrEF and PH-HFpEF.
All in all, the findings from these PH-HFrEF patients are comparable to what was previously reported in PH-HFpEF, Tectonic said. In both patient populations, no serious side effects of TX45 were reported.
“Similar to what was seen with TX45 in patients with PH-HFpEF, this study in patients with PH‑HFrEF demonstrated clinically important changes across multiple hemodynamic [blood flow] measures, showing the broad potential of TX45 across different patient populations with pulmonary hypertension associated with heart failure,” said John Teerlink, MD, a professor at the University of California, San Francisco.
Teerlink said it was “encouraging to see that TX45 reduced PCWP along with the decrease in afterload on the right ventricle.” According to the researchers, this “appears to address the underlying pathologies [disease processes] of CpcPH that lead to impairment of exercise capacity, poor outcomes and increased mortality in both PH‑HFrEF and PH‑HFpEF.”
Similar to what was seen with TX45 in patients with PH-HFpEF, this study in patients with PH‑HFrEF demonstrated clinically important changes across multiple [blood flow] measures, showing the broad potential of TX45 across different patient populations with pulmonary hypertension associated with heart failure.
Tectonic is now running a Phase 2 trial called APEX (NCT06616974) to further test TX45 in people with PH‑HFpEF. Depending on the findings of that ongoing study, the company is hoping to also further develop the therapy for PH‑HFrEF.
“These results in PH‑HFrEF open up the potential to expand into this additional patient population with significant unmet need and no approved therapies, pending results from the ongoing APEX Phase 2 clinical trial,” Reicin said.
Tectonic also recently announced plans to test TX45 in people with pulmonary hypertension and interstitial lung disease, when blood pressure in the lungs is elevated as a complication of disorders that cause lung inflammation and scarring.
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