SYLVANT Clinical Data
Efficacy & Safety
Proven clinical efficacy in patients with iMCD
The efficacy of SYLVANT® (siltuximab) has been proven in a randomized placebo-controlled clinical trial conducted in patients with iMCD.1
SYLVANT met its primary endpoint of durable tumor and symptomatic response1,2
- Durable tumor and symptomatic response with SYLVANT plus best supportive care (BSC) observed in 34% of patients compared to 0% with placebo plus BSC1: (95% CI: 11.1, 54.8; P=0.0012)
- The median duration of durable tumor and symptomatic response with SYLVANT was 383 days (range: 232-676 days)1
- Baseline IL-6 levels were not associated with durable tumor and symptomatic response or best tumor response1
- Study was conducted before diagnostic criteria for iMCD were established1,3
IL-6, interleukin-6; ITT, intent to treat.
SYLVANT met secondary endpoints of tumor response and days to treatment failure1,2
Hemoglobin levels rapidly increased with SYLVANT1
of anemic patients (n=19/31)e achieved >15 g/L increase with SYLVANT (95% CI: 28.3‑85.1; P=0.0002)1,2
of anemic patients (n=13/31)e achieved normalized hemoglobin with SYLVANT1
- Normalized hemoglobin achieved was assessed per a post-hoc analysis.
- This analyzed data was not powered for statistical analysis and should be considered descriptive only.
Measures of durable efficacy and treatment response with SYLVANT
Adapted from Clinical Study Report CNTO328MCD2001. June 2013. Recordati Rare Diseases, Inc.
In the placebo group, median time to durable symptomatic response was not reached.1
BSC, best supportive care; CI, confidence interval; ITT, intent to treat; NE, not estimable.
These are exploratory endpoints. The data should be considered descriptive only and no conclusions can be drawn.
Key biomarkers of inflammation decreased with SYLVANT1
Adapted from Clinical Study Report CNTO328MCD2001. June 2013. Recordati Rare Diseases, Inc.
BSC, best supportive care; CRP, C-reactive protein; ITT, intent to treat.
These are exploratory endpoints. The data should be considered descriptive only and no conclusions can be drawn.
CRP analyses were conducted to monitor and assess the pharmacodynamic effects of SYLVANT. ESR analysis was an evaluation to assess additional clinical benefit of SYLVANT. As these are exploratory endpoints, the data should be considered descriptive only and no conclusions can be drawn.
Safety and tolerability with SYLVANT was established in its
pivotal clinical trial2
Most common adverse events occurring in >10% of patients in any group through 8
infusions (safety populations)2
BSC, best supportive care.
Long-term Safety of SYLVANT
References:
1. van Rhee F, Wong RS, Munshi N, et al. Siltuximab for multicentric Castleman’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2014;15(9):966-974. 2. SYLVANT [package insert]. Hertfordshire, UK: EUSA Pharma (UK) Ltd; 2019. 3. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8–negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646-1657. 4. Data on file. Clinical Study Report CNTO328MCD2001. June 2013. Recordati Rare Diseases, Inc. 5. van Rhee F, Wong RS, Munshi N, et al. Siltuximab for multicentric Castleman’s disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2014;15(9):966-974; supplemental data.
INDICATIONS AND USAGE
SYLVANT® (siltuximab) is an interleukin-6 (IL-6) antagonist indicated 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.
Limitations of Use
SYLVANT was not studied in patients with MCD who are HIV positive or HHV-8 positive because SYLVANT did not bind to virally produced IL-6 in a nonclinical study.
IMPORTANT SAFETY INFORMATION
SYLVANT is contraindicated in patients experiencing a severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT. Hypersensitivity reactions, including anaphylactic reaction, hypersensitivity, and drug hypersensitivity have been reported in patients treated with siltuximab.
Concurrent Active Severe Infections: Do not administer SYLVANT to patients with severe infections until the infection resolves. SYLVANT may mask signs and symptoms of acute inflammation including suppression of fever and of acute Phase reactants such as C-reactive protein (CRP). Monitor patients receiving SYLVANT closely for infections. Institute prompt anti-infective therapy and do not administer further SYLVANT until the infection resolves.
Vaccinations: Do not administer live vaccines to patients or infants born to patients receiving SYLVANT because IL-6 inhibition may interfere with the normal immune response to new antigens.
Infusion Related Reactions and Hypersensitivity: SYLVANT may cause infusion-related reactions and anaphylaxis. Stop the infusion of SYLVANT if the patient develops signs of anaphylaxis. Discontinue further therapy with SYLVANT.
Stop the infusion if the patient develops a mild to moderate infusion reaction. If the reaction resolves, the SYLVANT infusion may be restarted at a lower infusion rate. Consider medicating with antihistamines, acetaminophen, and corticosteroids. Discontinue SYLVANT if the patient does not tolerate the infusion following these interventions.
Administer SYLVANT in a setting that provides resuscitation equipment, medication, and personnel trained to provide resuscitation.
Gastrointestinal (GI) Perforation: GI perforation has been reported in clinical trials although not in MCD trials. Use with caution in patients who may be at increased risk for GI perforation. Promptly evaluate patients presenting with symptoms that may be associated or suggestive of GI perforation.
The most common adverse reactions (>10% compared to placebo) during treatment with SYLVANT in the MCD clinical trial were rash, pruritus, upper respiratory tract infection, increased weight, and hyperuricemia.
To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases, Inc. at 1-888-575-8344, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug Interactions with Cytochrome P450 (CYP450) Substrates: Inhibition of IL-6 signaling in patients treated with SYLVANT may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment with SYLVANT.
Upon initiation or discontinuation of SYLVANT, in patients being treated with CYP450 substrates with a narrow therapeutic index, perform therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) as needed and adjust dose. The effect of SYLVANT on CYP450 enzyme activity can persist for several weeks after stopping therapy. Exercise caution when SYLVANT is co-administered with CYP3A4 substrate drugs where a decrease in effectiveness would be undesirable (e.g., oral contraceptives, lovastatin, atorvastatin).
Pregnancy and Lactation: SYLVANT may cause embryo-fetal harm when administered to pregnant women. Advise female patients of reproductive potential to use effective contraception during treatment with SYLVANT and for 3 months after the last dose. Advise patients not to breastfeed during treatment with SYLVANT and for 3 months after the final dose.
Pediatric Use: The safety and efficacy of SYLVANT have not been established in pediatric patients.
Dosing and Administration: Perform hematology laboratory tests prior to each dose of SYLVANT therapy for the first 12 months and every 3 dosing cycles thereafter. If treatment criteria outlined in Table 1 of the Prescribing Information are not met, consider delaying treatment with SYLVANT. Do not reduce dose.
SYLVANT® (siltuximab) for injection, for intravenous use, is available as 100 mg or 400 mg of lyophilized powder in a single-dose vial.
Please see the accompanying full Prescribing Information.
