Encouraging long-term outcomes observed in the treatment of PAH with sotatercept

Clinical benefit could be maintained during long-term therapy with sotatercept in patients with pulmonary arterial hypertension (PAH). Treatment-emergent discontinuations happened in 1.5% of the study participants.

Sotatercept is a first-in-class fusion protein that inhibits activin signalling and binds growth differentiation factors [1–3]. Investigated for the treatment of PAH, the drug improved both haemodynamic and clinical parameters in phase 2 and 3 trials [1]. Prof. Ioanna Preston (Tufts University School of Medicine, MA, USA) presented interim results of the first 409 patients included in SOTERIA (NCT04796337), an open-label follow-up trial that evaluates long-term results for safety, tolerability, and efficacy.
At baseline, a median age of 49 years and 81.9% of women were observed in the study cohort. Median time since being diagnosed with PAH was 8.1 years and over 90% of the participants were already on double or triple therapy. The median extent of drug exposure was 189 days in SOTERIA, but 462 days when including treatment within the parent trial.
“Very few treatment-emergent adverse events led to treatment discontinuation,” Prof. Preston declared, as treatment-emergent discontinuation and death were observed in 1.5% and 1.0%, respectively. Telangiectasia was seen in 22.7%, and it entailed a dose-hold or reduction in 4 patients. However, none of the telangiectasia cases were serious or led to discontinuation of treatment. “There were 12.2% epistaxis events, but only 1% was related to telangiectasia in the opinion of the investigator,” Prof. Preston added. She also reported thrombocytopenia in 3.7%. Moreover, 9 events of clinical worsening that included 3 PAH-related hospitalisations, occurred in 7 individuals.
As for clinical efficacy measures, including change from baseline in 6-minute walking test, NT-proBNP, WHO functional class, and percentage of achievement of a low French Risk Score, Prof. Preston stressed that the improvements seen at 6 months were largely sustained at the 1-year mark. Also, long-term treatment involved changes in the background therapy of the participants. Among 154 patients receiving intravenous prostacyclin, 22 were decreased and 9 increased in dosage (≥10%). “Of note, out of 272 patients on any prostacyclin, 8 patients have discontinued prostacyclin during SOTERIA,” Prof. Preston emphasised.
“The results of SOTERIA support the long-term durable benefit and safety of sotatercept for the treatment of PAH,” she noted in conclusion.

1. Preston I. Late Breaking Abstract - A long-term follow-up (LTFU) study of sotatercept for pulmonary arterial hypertension (PAH). Abstract 739, ERS 2023 International Congress, 9–13 September, Milan, Italy.
2. Souza R, et al. Eur Respir J. 2023;62(3):2301107.
3. Humbert M, et al. N Engl J Med. 2021;384(13):1204-1215.

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Posted on 29 October 202329 October 2023