Siltuximab (Sylvant, Janssen) is the first-ever drug to be approved by the US Food and Drug Administration (FDA) for the treatment of multicentric Castleman's disease (MCD), a rare blood disorder similar to lymphoma.
The drug underwent FDA priority review, 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.
MCD is estimated to affect about 1100 to 1300 Americans.
Siltuximab has been granted Orphan Drug Designation in both the United States and the European Union. It was recently recommended for approval in the European Union.
"There has been a serious need for treatment options for patients with MCD," said Frits van Rhee, MD, PhD, from the University of Arkansas for Medical Sciences in Little Rock, who headed the clinical trial that led to the drug's approval.
"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," Dr. van Rhee said in a statement. "Siltuximab gives physicians a long-awaited treatment option for a group of patients who has been suffering with this chronic, serious, and debilitating disease."
Abnormal Overgrowth of Lymphocytes
MCD results from an abnormal overgrowth of lymphocytes, leading to enlarged lymph nodes, but it can also affect lymphoid tissue of internal organs, causing the liver, spleen, or other organs to enlarge. Symptoms include fever, night sweats, weight loss, and weakness or fatigue, and because of the weakening of the immune system, patients become susceptible to infection. In fact, infection is a common cause of death in patients with MCD, as are multisystem organ failure and malignancies, including malignant lymphoma.
What causes the disease is not known, but it is associated with an overproduction of interleukin (IL)-6, and siltuximab acts as an IL-6 antagonist. It is administered by intravenous infusion once every 3 weeks.
The clinical trial that resulted in approval, known as MCD2001, was conducted in 79 patients with symptomatic MCD who were negative for HIV and human herpes virus 8. All participants received best supportive care, and they were randomized to also receive either siltuximab or placebo.
Results from this study showed that 34% of patients receiving siltuximab had a durable tumor and symptomatic response, compared with none on placebo (P = .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 for patients who received placebo was 134 days, but was not reached for patients on the drug (P < .05). Among anemic patients, an increase in hemoglobin of 1.5 g/dL was seen in 61% of patients in the siltuximab group versus none on placebo (P < .05).
These results "highlight the potential for siltuximab to be a new and valuable treatment option for MCD patients who, unfortunately, had no previously available treatment options," commented Raymond S. Wong, MBChB, MD, from the Prince of Wales Hospital and the Chinese University of Hong Kong, after he presented the study at the American Society of Hematology meeting in December 2013.
The most frequent adverse reactions (greater than 10% compared with placebo) during treatment with siltuximab in this trial were rash (28%), pruritus (28%), upper respiratory tract infection (26%), increased weight (19%), and hyperuricemia (11%). Warnings and precautions on the product label include concurrent active severe infections, administration of live vaccines, infusion-related reactions and hypersensitivity, and gastrointestinal perforation.
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Cite this: Siltuximab: First-Ever Drug for Castleman's Disease - Medscape - Apr 24, 2014.
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