Vials of siltuximab

Credit: Janssen Biotech, Inc.

The US Food and Drug Administration (FDA) has authorized marketing of siltuximab (Sylvant), the first drug approved to treat patients with multicentric Castleman’s disease (MCD) who are negative for human immunodeficiency virus (HIV) and human herpes virus 8 (HHV-8).

Siltuximab is a chimeric monoclonal antibody that binds to interleukin-6 (IL-6). Dysregulated overproduction of IL-6 has been implicated in the pathogenesis of MCD.

Siltuximab has not been studied in MCD patients who are HIV- or HHV-8 positive because the drug did not bind to virally produced IL-6 in a nonclinical study.

MCD is a rare blood disorder in which lymphocytes are overproduced, leading to enlarged lymph nodes. MCD can also affect lymphoid tissue of internal organs, causing enlargement of the liver, spleen, or other organs.

Patients with MCD have a high risk of death. Infections, multisystem organ failure, and malignancies such as lymphoma are common causes of death in patients with MCD.

“There has been a serious need for treatment options for patients with MCD,” said Frits van Rhee, MD, PhD, a professor at the University of Arkansas for Medical Sciences and lead investigator of the MCD2001 study.

“MCD is a complex disease, and, up until this point, physicians have tried to reduce lymph node masses and put the disease in remission through a combination of treatments, but MCD often returns. [The approval of siltuximab] gives physicians a long-awaited treatment option for [patients] suffering with this chronic, serious, and debilitating disease.”

The FDA reviewed siltuximab under its priority review program, which provides an expedited review for drugs that demonstrate the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. The drug was also granted orphan designation, as it is intended to treat a rare disease.

MCD2001: A phase 2 study of siltuximab

The FDA approval of siltuximab is based on results of the phase 2 MCD2001 trial. This randomized, double-blind, placebo-controlled study enrolled 79 patients with symptomatic MCD that was HIV- and HHV-8 negative.

Fifty-three patients were randomized to receive siltuximab at a dose of 11 mg/kg, plus best supportive care. The remaining 26 patients were randomized to receive placebo plus best supportive care.

The researchers defined a durable response as a tumor and symptomatic response that persisted for a minimum of 18 weeks without treatment failure. Thirty-four percent of patients in the siltuximab arm achieved this endpoint, but none of the patients in the placebo arm did (P=0.0012).

On the other hand, 4% of patients in the placebo arm experienced a tumor response, as did 38% of patients in the siltuximab arm (P<0.05).

The median time to treatment failure was not reached for patients in the siltuximab arm. But patients in the placebo arm experienced treatment failure at a median of 134 days (P<0.05).

The most frequent adverse events in siltuximab-treated patients (greater than 10% compared to placebo) were rash (28%), pruritus (28%), upper respiratory tract infection (26%), weight gain (19%), and hyperuricemia (11%).

Results of this study were presented at the 2013 ASH Annual Meeting and published in Blood. The study was sponsored by Janssen Research & Development, the company developing siltuximab.

Access to siltuximab

Siltuximab is marketed as Sylvant by Janssen Biotech Inc., which is based in Horsham, Pennsylvania. To promote access to the drug, Janssen has created the SylvantOne™ Support program.

The program offers services for providers and patients that can help assess insurance coverage and identify cost support options, such as the SylvantOne™ Patient Rebate Program for eligible commercial patients, as well as a potential option for those who are uninsured.

Patients and providers can contact SylvantOne™ Support by calling 1-855-299-8844.

Siltuximab is available in a 100-mg, single-use vial of lyophilized powder and a 400-mg, single-use vial of lyophilized powder. The recommended dose of siltuximab is 11 mg/kg given over 1 hour, via intravenous infusion, every 3 weeks.

For more information on siltuximab, see the full prescribing information.

FDA approves first drug for multicentric Castleman’s disease