Roivant Reports Phase 2 RESOLVE-Lung Study Results for Namilumab in Chronic Pulmonary Sarcoidosis

Kinevant Sciences, a clinical-stage biopharmaceutical company, announced that its Phase 2 study did not demonstrate the effectiveness of namilumab in treating patients with chronic active pulmonary sarcoidosis. This announcement was made on December 3, 2024.

The Phase 2 RESOLVE-Lung study (NCT05314517) was designed to evaluate the efficacy and safety of namilumab, an investigational anti-GM-CSF monoclonal antibody, administered once a month through a subcutaneous injection. The study enrolled 107 participants who had chronic active pulmonary sarcoidosis not well-controlled by existing treatments. The study took place across various sites in the U.S. and Europe.

The primary goal of the study was to assess the proportion of subjects experiencing a Rescue Event during the double-blind period. Unfortunately, namilumab failed to meet this primary endpoint. A Rescue Event was defined as a clinically significant worsening of sarcoidosis requiring additional treatment, failure to follow the protocol-defined corticosteroid tapering, or premature discontinuation from the study due to lack of benefit.

Secondary endpoints of the study also did not show treatment benefits. These included changes in percent predicted forced vital capacity, success in tapering corticosteroids, and changes in patient-reported outcomes using the King’s Sarcoidosis Questionnaire. Consistent with the primary endpoint, these secondary measures did not indicate any significant treatment advantage for namilumab.

In terms of safety, the profile of namilumab remained similar to previous studies, indicating no new safety concerns. However, given the lack of efficacy demonstrated in this study, Kinevant has decided to discontinue further development of namilumab for treating sarcoidosis.

Bill Gerhart, CEO of Kinevant, remarked on the disappointment of the study's outcome but emphasized the value of the data generated. He expressed gratitude to the patients, the Kinevant team, industry partners, principal investigators, site staff, and patient advocacy groups for their contributions to the study. Gerhart noted that the information obtained would be beneficial for future research in sarcoidosis.

Matt Gline, CEO of Roivant, acknowledged the inherent risks in clinical development and the importance of taking calculated risks to develop new medicines. He praised the thoughtful design of the RESOLVE-Lung study and its clear insights into the potential benefits of namilumab, despite the ultimate unfavorable results. Gline highlighted the importance of continued efforts in similar programs in the future.

Pulmonary sarcoidosis is a lung condition characterized by granulomas, which are clumps of immune cells of unknown cause. These granulomas can lead to symptoms such as breathlessness, fatigue, and pain. If not effectively treated, the inflammation can result in lung tissue scarring, dysfunction, and potentially lung failure. Chronic therapy is required for about half of the diagnosed patients to manage symptoms and prevent disease progression. Current treatments include oral steroids like prednisone and off-label immunosuppressive therapies such as methotrexate, which may not always be effective and can have serious side effects.

Approximately 200,000 individuals in the U.S. and over one million worldwide are estimated to have sarcoidosis. The disease can affect any organ, with about 90% of cases involving the lungs. GM-CSF is a pro-inflammatory cytokine implicated in several inflammatory diseases, including sarcoidosis. It is believed to play a critical role in recruiting macrophages and monocytes to the lung, initiating a granulomatous response.

Namilumab is an anti-GM-CSF monoclonal antibody designed for once-monthly subcutaneous administration. Despite the negative study results, the pursuit of treatments for sarcoidosis and other inflammatory diseases continues to be a priority for research and development in the biopharmaceutical field.