First Nationwide Look at Sotatercept Use in France Finds 257 Patients Treated Under Early Access

When sotatercept became available in France in June 2024, it arrived as the first of a new class of treatments for pulmonary arterial hypertension, a rare and progressive disease of the lung’s blood vessels. Now, a nationwide cohort study drawing on the French Health Data System has provided the first picture of how this drug has actually been used in routine clinical practice, describing 257 patients treated within the first 16 months of availability and documenting how their existing therapies changed after the new agent was added.

The study, published as a short communication in the journal Drugs – Real World Outcomes, was conducted by researchers using the National Early Access and Expensive Drugs Cohort, known as AP-MO, which is built from the French National Health Data System, or SNDS. This database contains pseudonymized individual-level data from the French health insurance system and the national hospital discharge database, covering nearly 99 percent of the French population. Because sotatercept was granted early access specifically for pulmonary arterial hypertension, the recorded treatment indication allowed the researchers to identify patients treated for that condition and to minimize misclassification with other forms of pulmonary hypertension.

The researchers included all patients who initiated sotatercept since the start of the early access program and followed them until 31 October 2025. In total, 257 patients were identified, with a median age of 53 years and an interquartile range of 41 to 67 years. Women made up 75.5 percent of the treated population. The median follow-up was 8.9 months, with an interquartile range of 5.3 to 12.9 months. All treatment costs were fully covered by the French national health insurance system under the early access mechanism.

Sotatercept is a first-in-class fusion protein administered by injection every three weeks as an add-on to existing pulmonary arterial hypertension therapy. The eligibility criteria for access in France broadened progressively over the course of the early access program, as reflected in three successive decisions by the Haute Autorité de Santé. The initial authorization was restricted to patients in World Health Organization functional class II or III on standard triple combination therapy that included a parenteral prostacyclin analogue. A first extension in January 2025 opened access to patients insufficiently controlled on oral tritherapy who were ineligible for parenteral prostacyclin, or who were on bitherapy and ineligible for another standard therapy. A further extension in September 2025 extended eligibility to patients in WHO functional class IV under similarly broadened conditions.

This progressive widening of the criteria helps explain the composition of the treated population. Before starting sotatercept, 66.5 percent of patients were receiving tritherapy, 25.3 percent bitherapy, and 6.6 percent monotherapy. Tritherapy most often combined a prostacyclin analogue, an endothelin receptor antagonist, and a phosphodiesterase-5 inhibitor. Alternative tritherapy regimens were more frequent among patients initiating treatment in 2025 than in 2024, at 28.6 percent versus 5.8 percent, while soluble guanylate cyclase stimulators were rarely prescribed. Among the alternative regimens, the most frequent combination was a selective prostacyclin receptor agonist plus an endothelin receptor antagonist and a phosphodiesterase-5 inhibitor.

The study also documented differences in the characteristics of patients starting treatment in 2024 versus 2025, which the authors suggest may reflect the evolving eligibility criteria, with broader background therapy requirements allowing a more clinically complex population in 2025. Patients initiating treatment in 2025 were slightly older and had a higher prevalence of chronic respiratory disease, at 33.9 percent versus 27.9 percent in 2024. Cardiovascular comorbidities showed mixed trends, with an overall decrease from 43 percent to 40.9 percent, driven by lower rates of cardiac rhythm or conduction disorders and acute heart failure, but a higher prevalence of chronic heart failure, at 16.4 percent versus 10.5 percent. The most frequent comorbidities overall were heart disease, affecting 41.6 percent of patients, and chronic respiratory disease, affecting 31.9 percent. The authors caution that some categories, such as heart disease or chronic respiratory disease, may partly overlap with manifestations of pulmonary arterial hypertension itself, including dyspnea, and that the approach does not allow definitive separation of disease-related manifestations from unrelated comorbid conditions.

A social gradient was also observed in the treated population, with 28.8 percent of patients falling in the most deprived quintiles of the social deprivation index, an ecological marker computed at the municipality level based on median household income, educational attainment, the share of manual workers, and unemployment. This gradient was weaker in 2025, at 26.3 percent, compared with 33.7 percent in 2024. The index was unavailable for a small proportion of patients residing in municipalities with very low population counts, for whom it could not be reliably calculated, and these patients were categorized as unknown for this variable.

To characterize how background therapy changed around the start of sotatercept, the researchers compared treatment regimens over three windows: the three months preceding initiation, the 30 days following initiation, and the subsequent two months. Among the 205 patients, or 79.7 percent of the cohort, who had at least 90 days of follow-up, background therapy remained unchanged across these sequential periods in approximately 67 percent of patients. The number of therapies increased in approximately 11 percent and decreased in approximately 9.5 percent, while the remaining patients showed more heterogeneous, nonmonotonic patterns reflecting alternating changes between bitherapy, tritherapy, and missing treatment data. The 90-day threshold was chosen because the recommended schedule of one injection every three weeks allows each patient sufficient time to receive the three injections required.

Administration patterns largely followed the expected schedule. Administrations generally adhered to the 21-day interval, and 193 patients, or 94.2 percent of those with at least 90 days of follow-up, received at least one dose renewal, meaning only 12 patients, or 5.8 percent, received a single sotatercept administration. In total, 75.6 percent received at least three administrations within the first three months, as recommended. Administration counts peaked in the third time window, a pattern the authors interpret as suggesting delayed dosing in some patients after earlier missed intervals. However, the clinical reasons for a lower-than-expected number of administrations, whether treatment discontinuation or temporary dosing delays, cannot be determined from the SNDS and were not further characterized in this descriptive study.

During follow-up, 13 deaths occurred, corresponding to an early mortality rate of 0.55 deaths per 100 person-months, and two patients underwent lung transplantation, at 2 and 7 months after sotatercept initiation. The authors emphasize that these findings describe treatment patterns rather than outcomes, and that further studies are warranted to assess the long-term effectiveness and safety of sotatercept in routine clinical practice. They also note limitations of the analysis: because of the small size of certain subgroups, specific switches between individual drug classes could not be reliably quantified, and dose adjustment could not be reliably assessed for all treatments, particularly parenteral prostacyclin analogues, whose dosing is titrated in nanograms per kilogram per minute, a level of precision not captured in the database. As a strength, the use of the SNDS provided a nationwide and near-exhaustive view of patients treated with sotatercept since the start of the early access program, offering the first comprehensive description of its use in routine care in France.

Subject of Research: Real-world use of sotatercept for pulmonary arterial hypertension in France

Article Title: Use of Sotatercept in France since Its Availability in June 2024: A Nationwide Study from the French Health Data System (SNDS)

Article References: Charifa, N., Weill, A., Zureik, M., Botton, J., & Haddy, N. (2026). Use of Sotatercept in France since Its Availability in June 2024: A Nationwide Study from the French Health Data System (SNDS). Drugs – Real World Outcomes. https://doi.org/10.1007/s40801-026-00579-1

Image Credits: AI Generated

DOI: 10.1007/s40801-026-00579-1

Keywords: sotatercept, pulmonary arterial hypertension, France, SNDS, early access program, drug utilization, real-world evidence, background therapy, dosing interval, cohort study, rare disease, pharmacoepidemiology