Rare Daily Staff
The China National Medical Products Administration has granted approval to BeiGene and EUSA Pharma’s Sylvant for the treatment of adult patients with the rare, life-threatening condition multicentric Castleman disease.
The approval is for patients with multicentric Castleman disease who are both human immunodeficiency virus negative and human herpes virus-8 negative.
Castleman disease describes a group of heterogeneous inflammatory disorders that all share a similar lymph node appearance under the microscope. In Castleman disease patients, inflammatory cells become hyper-activated and produce excess molecules (chemokines and cytokines), particularly Interleukin-6, that lead to flu-like symptoms, lymph node enlargement, and dysfunction of the bone marrow and vital organs including the liver and kidneys.
Siltuximab is a monoclonal antibody that directly neutralizes IL-6, an inflammatory cytokine detected at elevated levels in multiple inflammatory conditions. Sylvant is approved in a number of countries and regions and is indicated for the treatment of patients with multicentric Castleman disease.
“Today’s approval provides a new treatment for patients in China with this rare systemic disorder,” said Xiaobin Wu, president, chief operating officer, and general manager of China at BeiGene. “This approval is our second product in our collaboration with EUSA, highlighting the combined expertise of our companies as we work together on behalf of patients.”
The approval of siltuximab was supported by clinical results from a multinational, randomized, double blind, placebo-controlled phase 2 trial conducted in 79 patients from 19 countries and regions, including 16 patients from China.
The primary endpoint of the study was durable tumor and symptomatic response, defined as tumor response assessed by independent review and complete resolution or stabilization of prospectively collected iMCD symptoms, for at least 18 weeks without treatment failure. A statistically significant difference in independently reviewed durable tumor and symptomatic response rate in the siltuximab arm compared with the placebo arm (34 percent vs. 0 percent) was observed.
Data from all patients treated with siltuximab monotherapy form the overall basis of the safety evaluation. Infections (including upper respiratory tract infections), pruritus, rash, arthralgia, and diarrhea were the most common adverse reactions, occurring in greater than 20 percent of siltuximab-treated patients in iMCD clinical studies. The most serious adverse reaction associated with the use of siltuximab was anaphylactic reaction.
In the study, a total of 34 Asian patients were enrolled, including 16 from China; 24 of 34 Asian patients were treated in the siltuximab arm and the remaining 10 patients were treated in the placebo arm. The subgroup analyses showed that there was no significant difference in demographic and baseline disease characteristics between Asian patients and the overall patient population; the efficacy data on primary and secondary study endpoints of Asian patients was consistent with those of the overall patient population, and the same for safety data; no other safety signals were found.
An open label, long-term extension phase 2 trial was also conducted in patients with iMCD treated in prior trials. The median duration of siltuximab treatment was 5.52 years (range: 0.8 to 10.8 years); more than 50 percent of patients received siltuximab treatment for ≥5 years. The rate of serious or Grade ≥3 adverse events did not increase over time as a function of cumulative exposure.