Analysis Finds Winrevair Effective Across Cardiac Index Groups
A pooled analysis of two prior trials suggests patients with a variety of cardiac index scores saw improvement when Winrevair was added to background therapy.
A new pooled analysis of two Winrevair (sotatercept) trials suggests the first-in-class pulmonary arterial hypertension (PAH) therapy works regardless of the patient’s baseline hemodynamic characteristics.
The new analysis, which was published in the Journal of Heart and Lung Transplantation, offers a clearer picture of how Winrevair performs across cardiac index (CI) scores.
The phase 2 PULSAR trial, published in 2021, and the phase 3 STELLAR trial, released last year, both showed Winrevair led to improved outcomes in patients when added to background therapy. Those improvements included the categories of six-minute walking distance (6MWD), pulmonary vascular resistance, and, in the case of STELLAR, time to clinical worsening. The trials both found Winrevair had a manageable safety profile.
However, corresponding author Mardi Gomberg-Maitland, MD, MSc, of George Washington University, and colleagues, added that the efficacy of vasoactive agents such as prostacyclin has been shown to vary depending on a patient’s baseline cardiac function.
“This variation in treatment response underscores the importance of considering cardiac function when assessing treatment options and expected outcomes in PAH management,” they wrote.
In an effort to understand whether cardiac function has a significant impact on Winrevair’s efficacy, Gomberg-Maitland and colleagues evaluated outcomes in 106 patients from PULSAR and 323 patients from STELLAR using two different CI thresholds: 2.0 L/min/m2 and 2.5 L/min/m2. Of the 429 total participants, 51 had CIs below 2.0 L/min/m2 and 179 had CIs below 2.5 L/min/m2.
The data showed that patients benefited from Winrevair compared to placebo regardless of their CI category. For example, Winrevair improved 6MWD by a range of 33.9 to 63.7 meters across all subgroups (P < 0.001), the authors found.
In terms of time to first occurrence of a worsening event or death, Winrevair outperformed placebo in patients with CI ≥2.5 (HR 0.12; P < 0.001), ≥2.0 (HR 0.13; P <0.001), and <2.5 (HR 0.21; P <0.001) L/min/m2. Every subgroup saw improvements in World Health Organization (WHO) functional class and European Society of Cardiology/European Respiratory Society risk scores.
“These results suggest that sotatercept provides meaningful clinical benefits across CI subgroups, supported by improvements in exercise capacity, cardiopulmonary hemodynamics, outcomes, and other key clinical measures,” the investigators said.
Still, Gomberg-Maitland and colleagues said certain differences were noted between subgroups. For instance, only the ≥2.0 and <2.5 L/min/m2 subgroups showed improvement in right ventricular fractional area change (RVFAC). The investigators noted, though, that the <2.0 L/min/m2 cohort was small in size, and patients with CIs above 2.5 L/min/m2 had limited room for potential further improvement.
Gomberg-Maitland and colleagues added that the pooled analysis was based on heavily pretreated adults with WHO Functional Class II and III PAH. That, coupled with small sample sizes in some cohorts, mean that the findings are not necessarily generalizable across all patient groups.
The authors also cautioned that CI changes should not be interpreted in isolation.
“[It is important to recognize that CI increases or decreases are not inherently positive or negative, but rather should be evaluated in the context of the patient’s overall condition and metabolic demands,” they wrote.
Still, the investigators said the consistent benefits across multiple endpoints and various CI categories are encouraging and support the idea that the risk-benefit ratio of Winrevair is favorable.
“Taken together, these findings support the use of sotatercept in PAH patients across all levels of CI,” they concluded.
