The FDA ( Food and Drug Administration ) has approved Sylvant ( Siltuximab ) for the treatment of patients with multicentric Castleman’s disease ( MCD ) who are human immunodeficiency virus ( HIV ) negative and human herpesvirus-8 ( HHV-8 ) negative.
Sylvant was not studied in patients with MCD who are HIV positive or HHV-8 positive because Sylvant did not bind to virally produced interleukin-6 ( IL-6 ) in a nonclinical study.
Sylvant is an IL-6 antagonist biologic therapy administered as an intravenous ( IV ) infusion once every three weeks.
MCD is a rare blood disorder with high morbidity in which lymphocytes, a type of white blood cell, are over-produced, leading to enlarged lymph nodes. MCD can also affect lymphoid tissue of internal organs, causing the liver, spleen or other organs to enlarge.
Infections, multisystem organ failure and malignancies including malignant lymphoma are common causes of death in patients with MCD.
A recent U.S. analysis estimates the incidence of MCD at approximately 1,100 to 1,300 Americans.
While the cause of MCD currently is unknown, overproduction of IL-6 is considered a key mechanism in MCD. Siltuximab works by binding to human IL-6, a multifunctional cytokine produced by various cells such as T cells, B cells, monocytes, fibroblasts and endothelial cells.
The efficacy and safety of Siltuximab were evaluated in a multi-national, randomized, double-blind, placebo-controlled pivotal study in 79 patients with MCD ( MCD2001 ).
Fifty-three patients were randomized to the Siltuximab arm at a dose of 11 mg/kg and 26 patients were randomized to the placebo arm. Patients had symptomatic MCD and were HIV negative and HHV-8 negative.
Treatment of MCD tumors and related symptoms is an important treatment goal for these patients.
In this pivotal study more than one-third of patients in the Siltuximab arm had a durable tumor and symptomatic response to treatment plus best supportive care ( BSC ), compared to none of the patients who received placebo plus BSC ( 34% versus 0%; p=0.0012 ).
A durable response was defined as tumor and symptomatic response ( reduction in tumor size and disease symptoms ) that persisted for a minimum of 18 weeks without treatment failure.
The median time to treatment failure was not reached for patients who received Siltuximab plus BSC; those who received placebo plus BSC experienced treatment failure at a median of 134 days ( p less than 0.05).
Efficacy results from MCD2001 also showed tumor response for those in the Siltuximab arm was 38% versus 4% for those in the placebo arm ( p less than 0.05 ).
Among anemic patients, an increase in hemoglobin of 1.5 g/dL was seen in 61% of patients in the Siltuximab arm versus 0% in patients who received placebo and BSC ( p less than 0.05 ).
The warnings and precautions for Siltuximab include concurrent active severe infections, administration of live vaccines, infusion related reactions and hypersensitivity and gastrointestinal perforation.
The most frequent adverse reactions ( greater than 10% compared to placebo ) during treatment with Siltuximab in the MCD clinical trial were rash ( 28% ), pruritus ( 28% ), upper respiratory tract infection ( 26% ), increased weight ( 19% ) and hyperuricemia ( 11% ).
Source: Janssen Biotech, 2014