SATISFY-JP: Satralizumab Improves PVR in Patients With PAH, With Yuichi Tamura, MD, PhD

Satralizumab, an investigational anti-interleukin-6 (IL-6) receptor antibody, improved pulmonary vascular resistance in patients with pulmonary arterial hypertension (PAH) at 24 weeks during the SATISFY-JP trial.1

Presented at the American Heart Association’s Scientific Sessions 2025 in New Orleans, Louisiana, by Yuichi Tamura, MD, PhD, associate professor of cardiology at the International University of Health and Welfare School of Medicine, these trial results highlight the validity of this novel precision medicine strategy in addressing another specific subset of patients with PAH.1

SATISFY-JP was a multicenter, single-arm, open-label phase 2 study including patients with a confirmed diagnosis of Group 1 PAH classified as WHO Functional Class I, II, or III, an immune-responsive phenotype, treatment with 1-3 PAH drugs on a stable dose for ≥90 days before enrollment, and hemodynamic parameters with mean pulmonary arterial pressure ≥25 mmHg and a PVR >5 Wood units at rest in the 30 days prior to inclusion.2

A total of 20 patients with high-sensitivity IL-6 were included in the study, with a baseline age of 59.3 years and a distribution by WHO class of 5 patients in class II and 15 in class III. Patients were administered satralizumab 120 mg subcutaneously at weeks 0, 2, 4, and every 4 weeks thereafter. The primary endpoint of percent change in PVR was measured in 17 patients, showing a 17.4% reduction in PVR from baseline to week 24.2

For further insight into these data, the editorial team at HCPLive sat down for a discussion with Tamura in the following Q&A:

HCPLive: During the trial, a 17.4% reduction in PVR was observed. In the context of PAH, how clinically meaningful is this magnitude of change—particularly compared with what we typically see with established vasodilator therapies?

Tamura: Yeah, all the patients had already received vasodilator therapy, at least one pill, but most of the patients, around the 80% of the patients has already double or triple combination therapy, and this is a top-up therapy for normal therapies. So this is an additional therapy for the classical vasodilator therapy, and we obtained more improvement from these therapies.

HCPLive: Given that most PAH patients are already on multiple vasodilators, how do you envision anti-IL-6 therapy being integrated—additively, sequentially, or in a maintenance phase?

Tamura: For patients in this trial, prior therapy for the immunomodulation failed because some patients are responders and some aren’t. So, before the clinical trial, we tested the registry data, including serum cytokine levels, and we identified immunomodulation responsive cohorts with an AI based classification. In our study, our innovative point is that we only focused on patients with a higher IL-6 level.

HCPLive: IL-6 is just one cytokine implicated in PAH. Does this trial open the door for targeting other immune mediators in specific phenotypes?

Tamura: That’s a very good point. Because PAH patients are very heterogeneous, some patients have very high levels of IL-6 and IL-6 neighborhood cytokines. However. there are another kinds of cytokines which have already been identified, like an iron beta or other kind of cytokines. So the phenotype is already defined in each case. Some patients might derive benefit from an IL-6 blockage, and another patient may benefit with another immunomodulation or another cytokine based therapy.

HCPLive:IL-6 blockade carries potential immunologic risks. What safety signals should clinicians be most attentive to if this therapy becomes more widely available for PAH?

Tamura:As for our studies, we identified around 40% of the PAH patient have a higher IL-6 level, which is associated with concomitant cytokines. It is very good point to make regarding previous therapy like in our trials. It's very important to identify, prior to a clinical trial, what kinds of cytokines or chemokines may appear.

References

1. Tamura Y, Takumi I, Kohtaro A, et al. SATISFY-JP Trial: Satralizumab, an Anti-Interleukin-6 Receptor Antibody, for Pulmonary Arterial Hypertension with an Activated Immune-Responsive Phenotype: Primary Results from the Phase II Trial. Presented at the American Heart Association’s Scientific Sessions 2025. New Orleans, Louisiana. November 8-10, 2025.

2. Tamura Y, Takeyasu R, Takata T, et al. SATISFY-JP, a phase II multicenter open-label study on Satralizumab, an anti-IL-6 receptor antibody, use for the treatment of pulmonary arterial hypertension in patients with an immune-responsive-phenotype: Study protocol. Pulm Circ. 2023;13(2):e12251. Published 2023 Jun 19. doi:10.1002/pul2.12251