FDA Approval for Siltuximab
Brand name(s): Sylvant™
- Approved for multicentric Castleman disease in HIV- and HHV8-negative patients
Full prescribing information is available, including clinical trial information, safety, dosing, drug–drug interactions, and contraindications.
On April 23, 2014, the Food and Drug Administration (FDA) approved siltuximab (SylvantTM Injection, made by Janssen Biotech, Inc.) for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus 8 (HHV8) negative.
The approval was based on an international multicenter randomized phase 2 study that compared intravenous infusions of siltuximab and best supportive care (BSC) to placebo and BSC. The trial enrolled 79 patients and randomly assigned 53 patients to receive siltuximab plus BSC and 26 patients to receive placebo plus BSC. Siltuximab was administered every 3 weeks as an intravenous infusion at a dose of 11 mg/kg.
The trial met its primary endpoint of "durable tumor and symptomatic response," defined as a partial or complete response assessed by independent review and complete resolution or stabilization of MCD symptoms. Thirty-four MCD-related symptoms were prospectively identified and collected and graded (according to NCI Common Terminology Criteria for Adverse Events v4) by the investigator. A durable response was defined as a tumor and symptomatic response that persisted for a minimum of 18 weeks without treatment failure. The durable tumor and symptomatic response rates were 34 percent (18/53) versus 0 percent (0/26) for the siltuximab and placebo groups, respectively [(95 percent CI: 11.1, 54.8); p=0.0012].
Additional prespecified endpoints included tumor response, time to treatment failure, and an increase in hemoglobin of at least 1.5 grams/dL at week 13 in patients who were anemic at study entry. Tumor response rates were 38 percent in the siltuximab group versus 4 percent in the placebo group (p<0.05). The median time to treatment failure, after a median follow-up of 422 days, was not reached in the siltuximab arm and was 134 days in the placebo arm [HR 0.418 (95 percent CI: 0.21 to 0.82); p <0.05]. An increase in the level of hemoglobin described above was observed in 19 patients on the siltuximab arm and no patients on the placebo arm [(95 percent CI: 28.3, 85.1); p <0.05].
The most common adverse reactions during treatment with siltuximab (more than 10 percent compared to placebo) were severe itching, increased weight, rash, hyperuricemia, and upper respiratory tract infection.
The recommended dose and schedule for siltuximab is 11 mg/kg dose given over 1 hour by intravenous infusion every 3 weeks.
This summary was provided by Richard Pazdur, M.D., director of the FDA's Office of Hematology and Oncology Products.
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.