Drugs Xagena
The FDA ( Food and Drug Administration ) has approved Siltuximab ( Sylvant ), for the treatment of patients with multicentric Castleman’s disease ( MCD ) who are human immunodeficiency virus ( HIV- ) -negative and human herpes virus -8 ( HHV-8 ) -negative.
The approval was based on an international, multicenter, randomized ( 2:1 ), phase 2 study comparing every three-week intravenous infusions of Siltuximab and best supportive care ( BSC ) to placebo and BSC.
The trial enrolled 79 patients and randomly allocated 53 patients to the Siltuximab arm plus best supportive care and 26 patients randomized to the placebo arm plus best supportive care.
Siltuximab was administered every three 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 tumor response ( partial and complete responses ) assessed by independent review and complete resolution or stabilization of MCD symptoms.
Thirty-four MCD related symptoms were prospectively identified and collected and graded ( NCI-CTAEv4 ) 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% ( 18/53 ) versus 0% ( 0/26 ) for the Siltuximab and placebo groups, respectively ( p=0.0012 ).
Additional supportive pre-specified 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% versus 4% for the Siltuximab and placebo groups, respectively ( p less than 0.05 ).
The median time- to- treatment failure, with a median follow-up of 422 days, was not reached in the Siltuximab arm and was 134 days in the placebo arm ( hazard ratio, HR=0.418; p less than 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 ( p less than 0.05 ).
The common adverse reactions ( greater than 10% compared to placebo ) during treatment with Siltuximab were pruritus, 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. ( Xagena )
Source: FDA, 2014
XagenaMedicine_2014
