Novel immunomodulator offers hope to reduce steroid dependency in sarcoidosis

The immunomodulator efzofitimod has recently undergone evaluation in a phase 1b/2a multiple-ascending-dose study, where it was able to reduce steroid dependency in patients suffering from chronic pulmonary sarcoidosis. These positive results set the stage for a phase 3 trial that will further elucidate the benefit of efzofitimod for patients suffering from this rare condition.

The phase 1b/2a study randomised 37 patients with chronic pulmonary sarcoidosis to treatment with efzofitimod or placebo [1]. At baseline, study participants were on stable (≥ 4 weeks) oral corticosteroids (prednisone equivalent 10 to 25 mg/day). The placebo and subtherapeutic efzofitimod arm (1 mg/kg) were pooled in this post-hoc analysis. The participants received 6 intravenous doses over a 24-week period, with the goal of tapering oral steroid use to 5 mg/day by week 8. Three main endpoints were investigated: steroid tapering, lung function improvement, and patient-reported outcomes (PROs). Inclusion criteria encompassed patients aged 18–75 years, a weight between 40 kg and 160 kg, documented sarcoidosis, lung involvement, specific symptom severity, and a willingness to attempt steroid taper.

The data revealed compelling evidence regarding the efficacy of efzofitimod. Notably, 7.7% of the participants in the therapeutic group relapsed, compared with 54.4% in the placebo/subtherapeutic group (P=0.017). This marked difference demonstrates efzofitimod's potential to reduce steroid dependency. Moreover, lung function, as measured by forced vital capacity (FVC), significantly improved in the therapeutic group (P=0.035). PROs, assessed through King’s Sarcoidosis Questionnaire – Lung (KSQ-L) scores, also favoured the therapeutic group. Over half (52.9%) of the patients in this group exhibited a significant and clinically relevant increase (≥12), 3 times the minimal clinically important differences (MCID), compared with only 15.0% in the subtherapeutic group (P=0.032).

Adverse events were also monitored closely, with notable mentions including the development of antibodies, infusion-related reactions, and newly occurring malignancies.

This study presents evidence of efzofitimod's effectiveness in reducing steroid dependency and improving lung function and PROs in patients with pulmonary sarcoidosis. These findings helped lay the groundwork for the phase 3 EFZO-FIT (NCT05415137) study, which will aim to confirm and expand upon these results.

1. Chandrasekaran A, et al. Therapeutic doses of Efzofitimod significantly improve multiple pulmonary sarcoidosis efficacy measures. Abstract 1744, ERS International Congress 2023, 9–13 September, Milan, Italy.

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Posted on 29 October 202329 October 2023