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Spesolimab-sbzo, an interleukin-36 receptor antagonist, is a humanized monoclonal IgG1 antibody (mAb) against human IL-36R produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. Spesolimab-sbzo has a molecular weight of approximately 146 kDa.
SPEVIGO (spesolimab-sbzo) injection is a sterile, preservative-free, colorless to slightly brownish-yellow, clear to slightly opalescent solution supplied in a single-dose vial for intravenous infusion. Each 7.5 mL vial contains 450 mg spesolimab-sbzo, arginine hydrochloride (39.5 mg), glacial acetic acid (2.4 mg), polysorbate 20 (3.0 mg), sodium acetate (24.5 mg), sucrose (386 mg), and Water for Injection, USP with a pH of 5.0-6.0.
SPEVIGO is indicated for the treatment of generalized pustular psoriasis (GPP) in adults and pediatric patients 12 years of age and older and weighing at least 40 kg.
Evaluate patients for active or latent tuberculosis (TB) infection. SPEVIGO initiation is not recommended in patients with active TB infection. Consider initiating treatment of latent TB prior to initiation of SPEVIGO [see WARNINGS AND PRECAUTIONS].
Complete all age-appropriate vaccinations according to current immunization guidelines prior to initiating SPEVIGO for treatment of GPP [see WARNINGS AND PRECAUTIONS].
The recommended dosage of SPEVIGO for treatment of GPP when not experiencing a flare in adults and pediatric patients 12 years of age and older and weighing at least 40 kg is a loading dose of 600 mg (four 150 mg injections) followed by 300 mg (two 150 mg injections) administered subcutaneously 4 weeks later and every 4 weeks thereafter.
With Intravenous SPEVIGO Four weeks after treatment of a GPP flare with intravenous SPEVIGO [see DOSAGE AND ADMINISTRATION], initiate or reinitiate subcutaneous SPEVIGO for treatment of GPP at a dose of 300 mg (two 150 mg injections) administered every 4 weeks. A subcutaneous loading dose is not required following treatment of a GPP flare with intravenous SPEVIGO.
The recommended dosage of SPEVIGO for treatment of GPP flare in adults and pediatric patients 12 years of age and older and weighing at least 40 kg is a single 900 mg dose administered by intravenous infusion over 90 minutes.
If GPP flare symptoms persist, an additional intravenous 900 mg dose (over 90 minutes) may be administered one week after the initial dose.
Parenteral drug products should be inspected visually for particulate matter and discoloration, whenever solution and container permits. SPEVIGO is a colorless to slightly brownish-yellow, clear to slightly opalescent solution. Do not use if the solution is cloudy, discolored, or contains large or colored particulates.
Preparation
Administration
SPEVIGO is a colorless to slightly brownish-yellow, clear to slightly opalescent solution available as:
SPEVIGO (spesolimab-sbzo) injection is a sterile, preservative-free, colorless to slightly brownish-yellow, clear to slightly opalescent solution available as follows:
NDC Number 0597-0620-20: Each carton contains two single-dose 150 mg/mL prefilled syringes.
NDC Number 0597-0035-10: Each carton contains two single-dose 450 mg/7.5 mL (60 mg/mL) glass vials.
Manufactured by: Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT 06877 USA US License Number 2006. Revised: Mar 2024
The following adverse reactions are discussed in greater detail in other sections of the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
SPEVIGO was studied in Study Effisayil-1, a randomized, double-blind, placebo-controlled study comparing a single intravenous 900 mg dose of SPEVIGO (n=35) with placebo (n=18) in subjects with generalized pustular psoriasis (GPP) flare. Subjects in either treatment group who continued to experience flare symptoms at Week 1 were eligible to receive a single open-label intravenous dose of 900 mg of SPEVIGO (second dose and first dose for subjects in the SPEVIGO and placebo groups, respectively). At Week 1, 12 (34%) subjects and 15 subjects (83%) in the SPEVIGO and placebo groups, respectively, received open-label SPEVIGO. After Week 1 to Week 12, subjects in either treatment group whose GPP flare reoccurred after achieving a clinical response were eligible to receive a single open-label rescue intravenous dose of 900 mg of SPEVIGO, with a maximum of 3 total doses of SPEVIGO throughout the study. Six subjects received a single open-label rescue dose of SPEVIGO. Thirty-six subjects received 1 dose of SPEVIGO, 13 subjects received 2 doses of SPEVIGO, and 2 subjects received 3 doses of SPEVIGO throughout the study [see Clinical Studies].
Subjects ranged in age from 21 to 69 years (mean age of 43 years); 45% were White and 55% were Asian; and 68% were female.
Table 1 summarizes selected adverse reactions that occurred at a rate of at least 1% and at a higher rate in the intravenous SPEVIGO group than in the placebo group through Week 1.
Table 1 : Selected Adverse Reactions Occurring in ≥1% of the Intravenous SPEVIGO Group and More Frequently than in the Placebo Group through Week 1 in Subjects with GPP Flare (Study Effisayil-1)
| Adverse Reaction | Intravenous SPEVIGO N = 35 n (%) |
Placebo N = 18 n (%) |
| Asthenia and Fatigue | 3 (9) | 0 |
| Nausea and Vomiting | 3 (9) | 1 (6) |
| Headache | 3 (9) | 1 (6) |
| Pruritus and prurigo | 2 (6) | 0 |
| Infusion site hematoma and bruising | 2 (6) | 0 |
| Urinary tract infection | 2 (6) | 0 |
| Bacteremia | 1 (3) | 0 |
| Bacteriuria | 1 (3) | 0 |
| Cellulitis | 1 (3) | 0 |
| Herpes dermatitis and oral herpes | 1 (3) | 0 |
| Upper respiratory tract infection | 1 (3) | 0 |
| Dyspnea | 1 (3) | 0 |
| Eye edema | 1 (3) | 0 |
| Urticaria | 1 (3) | 0 |
The most frequent adverse reactions that occurred in subjects treated with intravenous SPEVIGO were infections. During the 1-week placebo-controlled period in Study Effisayil-1, infections were reported in 14% of subjects treated with SPEVIGO compared with 6% of subjects treated with placebo. Serious infection (urinary tract infection) was reported in 1 subject (3%) treated with SPEVIGO and no subjects treated with placebo. Infections observed through Week 1 in Study Effisayil-1 in subjects treated with SPEVIGO were mild (29%) to moderate (71%).
Two cases of DRESS were reported in Study Effisayil-1 in subjects with GPP who were treated with intravenous SPEVIGO. RegiSCAR DRESS validation scoring (with the following categories: “no”, “possible”, “probable”, or “definite” DRESS) was applied to the reported cases. Reported cases were assessed as “no DRESS” and “possible DRESS”.
In Study Effisayil-1, additional adverse reactions that occurred through Week 12 in subjects treated with 1 single intravenous dose of randomized SPEVIGO were mild to moderate infections: device-related infection (3%), subcutaneous abscess (3%), furuncle (3%), and influenza (3%).
Additional adverse reactions that occurred through Week 17 in subjects treated with a single intravenous dose of open-label SPEVIGO at Week 1 (second dose and first dose for subjects in the SPEVIGO and placebo groups, respectively) were mild to moderate infections: otitis externa (7%), vulvovaginal candidiasis (4%), vulvovaginal mycotic infection (4%), latent tuberculosis (4%), diarrhea (11%), and gastritis (4%). No new adverse reactions were identified for up to 16 weeks in subjects treated with a single intravenous dose of open-label rescue SPEVIGO from Week 1 to Week 12 (range 1-3 total doses).
Subcutaneous treatment with SPEVIGO was studied in Study Effisayil-2, a randomized, placebo-controlled, double-blind, parallel group study evaluating three dosages of SPEVIGO or placebo in subjects with generalized pustular psoriasis (GPP). Subjects were randomized (1:1:1:1) to receive a 600 mg loading dose (LD) of SPEVIGO followed by 300 mg every 4 weeks (n=30), one of two other dosages of SPEVIGO, or placebo (n=30) for up to 48 weeks [see Clinical Studies].
Subjects ranged in age from 14 to 75 years (mean age was 40 years); 64% of subjects were Asian and 36% were White; 62% of subjects were female.
Regarding the exposure-adjusted incidence rates for subjects on randomized treatment prior to receiving rescue treatment for flare or completing trial without a flare, the rate per 100-patient years for injection site reaction (including erythema, pain, swelling, induration, urticaria, and warmth at the injection site) was 31.6 for the subcutaneous SPEVIGO cohort (600 mg LD followed by 300 mg every 4 weeks) compared to 12.7 for the placebo cohort.
Regarding the exposure-adjusted incidence rates for subjects on randomized treatment prior to receiving rescue treatment for flare or completing trial without a flare, the rate per 100-patient years for urinary tract infection was 18 for the subcutaneous SPEVIGO cohort (600 mg LD followed by 300 mg every 4 weeks) compared to 0 for the placebo cohort.
Regarding the exposure-adjusted incidence rates for subjects on randomized treatment prior to receiving rescue treatment for flare or completing trial without a flare, the rate per 100-patient years for pruritus was 8.8 for the subcutaneous SPEVIGO cohort (600 mg LD followed by 300 mg every 4 weeks) compared to 0 for the placebo cohort.
Regarding the exposure-adjusted incidence rates for subjects on randomized treatment prior to receiving rescue treatment for flare or completing trial without a flare, the rate per 100-patient years for arthralgia was 13.3 for the subcutaneous SPEVIGO cohort (600 mg LD followed by 300 mg every 4 weeks) compared to 6 for the placebo cohort.
For subjects on randomized treatment prior to receiving rescue treatment for flare or completing trial without flare, there were 3 subjects who discontinued subcutaneous SPEVIGO in the subcutaneous SPEVIGO cohort (600 mg LD followed by 300 mg every 4 weeks) due to treatment emergent adverse events of psoriasis compared to no subjects in the placebo cohort who discontinued placebo for any treatment emergent adverse event.
In Effisayil-2, subjects who experienced a GPP flare and received at least one dose of an open-label single intravenous 900 mg dose of SPEVIGO were treated with open-label subcutaneous SPEVIGO 300 mg. These subjects (n=19) received subcutaneous dosing at every 12 weeks which could have been increased to every 4 weeks based on GPPPGA total score or pustulation sub score increased by >1 from any previous OL maintenance visit. The reported safety profile of open-label subcutaneous SPEVIGO use after treatment of GPP flare with open-label intravenous SPEVIGO use was consistent with the safety profiles of use of SPEVIGO from Trial Effisayil-1 and randomized controlled data from Trial Effisayil-2.
Among approximately 835 subjects exposed to spesolimab-sbzo during clinical development, Guillain-Barre syndrome (GBS) was reported in 3 subjects who received various doses of spesolimab-sbzo via various methods of administration in clinical studies for unapproved indications.
No Information provided
Included as part of the PRECAUTIONS section.
SPEVIGO may increase the risk of infections. During the one-week placebo-controlled period in the Effisayil-1 trial, infections were reported in 14% of subjects treated with SPEVIGO compared with 6% of subjects treated with placebo [see ADVERSE REACTIONS].
In patients with a chronic infection or a history of recurrent infection, consider the potential risks and expected clinical benefits of treatment prior to prescribing SPEVIGO. Treatment with SPEVIGO is not recommended in patients with any clinically important active infection until the infection resolves or is adequately treated. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur during or after treatment with SPEVIGO. If a patient develops a clinically important active infection, discontinue SPEVIGO therapy until the infection resolves or is adequately treated.
Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with SPEVIGO. Avoid use of SPEVIGO in patients with active TB infection.
Consider initiating anti-TB therapy prior to initiating SPEVIGO in patients with latent TB or a history of TB in whom an adequate course of treatment cannot be confirmed. Monitor patients for signs and symptoms of active TB during and after SPEVIGO treatment.
SPEVIGO-associated hypersensitivity reactions may include immediate reactions such as anaphylaxis and delayed reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS).
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in clinical trials with SPEVIGO in subjects with GPP [see ADVERSE REACTIONS].
If a patient develops signs of anaphylaxis or other serious hypersensitivity, discontinue SPEVIGO immediately and initiate appropriate treatment. SPEVIGO is contraindicated in patients with severe or life-threatening hypersensitivity to spesolimab-sbzo or to any of the excipients in SPEVIGO [see CONTRAINDICATIONS].
If a patient develops mild or moderate hypersensitivity during an intravenous infusion or other infusion-related reactions, stop SPEVIGO infusion and consider appropriate medical therapy (e.g., systemic antihistamines and/or corticosteroids). Upon resolution of the reaction, the infusion may be restarted at a slower infusion rate with gradual increase to complete the infusion.
Prior to initiating SPEVIGO for treatment of GPP, complete all age-appropriate vaccinations according to current immunization guidelines.
Avoid use of live vaccines in patients during and for at least 16 weeks after treatment with SPEVIGO. No specific studies have been conducted in SPEVIGO-treated patients who have recently received live viral or live bacterial vaccines.
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).
Inform patients that SPEVIGO may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to the healthcare provider and contacting their healthcare provider if they develop any signs or symptoms of clinically important infection during or after treatment with SPEVIGO [see WARNINGS AND PRECAUTIONS].
Inform patients that hypersensitivity and infusion-related reactions may occur with SPEVIGO. Advise patients to seek immediate medical attention if they experience any symptoms of a serious hypersensitivity reaction [see WARNINGS AND PRECAUTIONS].
Advise patients to avoid receiving live vaccines during and for at least 16 weeks after treatment with SPEVIGO. Instruct patients to inform the healthcare provider that they are taking SPEVIGO prior to a potential vaccination [see WARNINGS AND PRECAUTIONS].
If a patient 12 years of age and older or caregiver is to administer subcutaneous SPEVIGO, instruct them on injection technique and assess their ability to inject subcutaneously to ensure the proper administration of SPEVIGO. Provide training to patients or caregivers on preparation and administration of subcutaneous SPEVIGO and on proper needle and syringe disposal [see DOSAGE AND ADMINISTRATION and Instructions For Use].
Instruct patients or caregivers to subcutaneously administer two 150 mg/mL prefilled syringes to achieve a complete 300 mg dose of SPEVIGO [see DOSAGE AND ADMINISTRATION and Instructions For Use].
Carcinogenicity and mutagenicity studies have not been conducted with spesolimab-sbzo.
No adverse effects on fertility were observed in male or female mice that were intravenously administered a surrogate antibody to IL36R at doses up to 50 mg/kg twice weekly.
The limited data on the use of SPEVIGO in pregnant women are insufficient to inform a drug-associated risk of adverse pregnancy-related outcomes. Human IgG is known to cross the placental barrier; therefore, SPEVIGO may be transmitted from the mother to the developing fetus. In an animal reproduction study, intravenous administration of a surrogate antibody against IL36R in mice during the period of organogenesis did not elicit any reproductive toxicity (see Data).
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Animal Data
Embryo-fetal development and pre-and postnatal development toxicity studies were performed in mice using a surrogate mouse specific IL36R antagonist monoclonal antibody. In the embryo-fetal development study, the surrogate was administered intravenously at doses up to 50 mg/kg to pregnant female mice twice weekly during the period of organogenesis. The surrogate was not associated with embryo-fetal lethality or fetal malformations. In the pre- and postnatal development toxicity study, the surrogate was administered intravenously at doses up to 50 mg/kg to pregnant female mice twice weekly from gestation day 6 through lactation day 18. There were no maternal effects observed. There were no treatment-related effects observed on postnatal developmental, neurobehavioral, or reproductive performance of offspring.
There are no data on the presence of spesolimab-sbzo in human milk, the effects on the breastfed infant, or the effects on milk production. Spesolimab-sbzo is a monoclonal antibody and is expected to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for SPEVIGO and any potential adverse effects on the breastfed infant from SPEVIGO or from the underlying maternal condition.
The safety and effectiveness of SPEVIGO for the treatment of GPP have been established in pediatric patients 12 years of age and older and weighing at least 40 kg. Use of SPEVIGO for this indication is supported by data from a randomized, placebo-controlled study which included 6 pediatric subjects 14 to 17 years of age with a history of GPP treated with subcutaneous SPEVIGO (Study Effisayil-2) and evidence from an adequate and well-controlled study of intravenous SPEVIGO in adults with GPP (Study Effisayil-1), with additional pharmacokinetic analyses showing similar drug exposure levels in adults and pediatric subjects 12 years of age and older and weighing 40 kg or more [see ADVERSE REACTIONS, CLINICAL PHARMACOLOGY, and Clinical Studies].
The safety and effectiveness of SPEVIGO in pediatric patients younger than 12 years of age or in pediatric patients weighing less than 40 kg have not been established.
There were 2 (6%) intravenous SPEVIGO-treated subjects 65 to 74 years of age and no subjects 75 years of age or older in Study Effisayil-1. There were 6 (7%) subcutaneous SPEVIGO-treated subjects 65 to 74 years of age and 1 (1%) subject 75 years of age in Study Effisayil-2. Clinical studies of SPEVIGO did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.
No Information provided
SPEVIGO is contraindicated in patients with severe or life-threatening hypersensitivity to spesolimab-sbzo or to any of the excipients in SPEVIGO. Reported hypersensitivity reactions have included drug reaction with eosinophilia and systemic symptoms (DRESS) [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].
Spesolimab-sbzo is a humanized monoclonal immunoglobulin G1 antibody that inhibits interleukin-36 (IL-36) signaling by specifically binding to the IL36R. Binding of spesolimab-sbzo to IL36R prevents the subsequent activation of IL36R by its ligands (IL-36 α, β and γ) and downstream activation of pro-inflammatory and proÂfibrotic pathways. The precise mechanism linking reduced IL36R activity and the treatment of flares of GPP is unclear.
The pharmacodynamics of SPEVIGO in the treatment of patients with GPP have not been fully characterized.
A population pharmacokinetic model was developed based on data collected from healthy subjects, patients with GPP, and patients with other diseases. After a single intravenous dose of 900 mg of SPEVIGO, the population PK model-estimated AUC0-∞(95% CI) and Cmax (95% CI) in a typical anti-drug antibody (ADA)Ânegative patient with GPP were 4750 (4510, 4970) mcg·day/mL and 238 (218, 256) mcg/mL, respectively. After subcutaneous SPEVIGO 600 mg LD followed by 300 mg every 4 weeks, the mean steady-state trough concentration ranged from 33.4 mcg/mL to 42.3 mcg/mL.
When administered intravenously, spesolimab-sbzo AUC increased dose-proportionally from 0.3 to 20 mg/kg, and CL and terminal half-life were independent of dose. Following subcutaneous single dose administration, spesolimab-sbzo exposure increased slightly more than dose-proportionally across the dose range of 150 mg to 600 mg due to increased bioavailability at higher doses.
Following subcutaneous single dose administration of SPEVIGO in healthy volunteers, peak plasma concentrations were achieved between 5.5 to 7 days after dosing. After subcutaneous administration in the abdomen, absolute bioavailability (90% CI) was slightly higher at higher doses with estimated values of 58 (51, 66)%, 65 (60, 69)%, and 72 (65, 79)% at 150 mg, 300 mg, and 600 mg, respectively. Based on limited data, absolute bioavailability (90% CI) in the thigh was approximately 85 (77, 94)% following a subcutaneous dose of 300 mg SPEVIGO.
Based on the population pharmacokinetic analysis, the typical total volume of distribution at steady state was 6.4 L.
Metabolism
The metabolic pathway of spesolimab-sbzo has not been characterized. As a humanized IgG1 monoclonal antibody, spesolimab-sbzo is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG.
Excretion
In the linear dose range (0.3 to 20 mg/kg), based on the population PK model, spesolimab-sbzo clearance (95% CI)in a typical GPP patient without ADA, weighing 70 kg was 0.184 (0.175, 0.194) L/day. The terminal half-life was 25.5 (24.4, 26.3) days.
Based on population pharmacokinetic analyses, age, gender, and race did not have an effect on the pharmacokinetics of spesolimab-sbzo.
As a monoclonal antibody, spesolimab-sbzo is not expected to undergo hepatic or renal elimination. No formal study of the effect of hepatic or renal impairment on the pharmacokinetics of spesolimab-sbzo was conducted.
Spesolimab-sbzo concentrations were increased in subjects with lower body weight and decreased in subjects with higher body weight. The clinical impact of body weight on spesolimab-sbzo plasma concentrations is unknown.
The pharmacokinetics of spesolimab-sbzo have not been studied in pediatric subjects below the age of 12 years. The plasma pharmacokinetics of spesolimab-sbzo observed in pediatric subjects 12 years of age and older and weighing 40 kg or more following subcutaneous administration were consistent with that observed in adults.
No formal drug interactions studies have been conducted with spesolimab-sbzo. In patients with GPP, spesolimab-sbzo is not expected to cause cytokine-mediated CYP interactions as a perpetrator.
The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of spesolimab-sbzo or of other spesolimab products.
In subjects with GPP treated with intravenous SPEVIGO in Study Effisayil-1, ADAs formed with a median onset of 2.3 weeks. Following administration of 900 mg intravenous SPEVIGO, (12/50) 24% of subjects had a maximum ADA titer greater than 4000 and were neutralizing antibody (Nab)-positive by the end of the study (Weeks 12 to 17). In Study Effisayil-2, ADAs formed with a median onset of 8 weeks. Following administration of a 600 mg subcutaneous LD of SPEVIGO followed by 300 mg every 4 weeks for a total duration of 48 weeks, 24% of subjects had a maximum ADA titer greater than 4000 and were Nab-positive.
In Study Effisayil-1 following intravenous SPEVIGO, females appeared to have higher immunogenicity response; the percentage of subjects with ADA titer greater than 4000 was 30% in females, and 12% in males, respectively. In Study Effisayil-2 following administration of subcutaneous SPEVIGO, the data on immunogenicity response in males versus females were inconclusive.
Anti-Drug Antibody Effects on Pharmacokinetics In subjects with ADA titers below 4000, there was no apparent impact on spesolimab-sbzo pharmacokinetics. In some subjects with ADA titer values greater than 4000, plasma spesolimab-sbzo concentrations were significantly reduced after reaching this ADA titer.
In Study Effisayil-1, there are limited data on the impact of ADAs on safety and efficacy upon retreatment as the majority of subjects did not experience a subsequent, new flare in an open-label extension study.
In subjects who received SPEVIGO 600 mg subcutaneous LD followed by 300 mg every 4 weeks in Study Effisayil-2, the mean trough concentrations beginning at Week 8 in ADA-positive subjects with titers greater than 4000 were approximately 77% to 107% of trough concentrations in subjects who were ADA-negative or ADA-positive with titer values less than 4000. After subcutaneous administration of SPEVIGO, there appears to be no impact of ADA presence on efficacy. This observation is based on limited numbers of ADA-positive subjects (N = 11). There are insufficient data to assess whether there is a clinically significant effect of ADAs on the safety of spesolimab-sbzo.
A randomized, double-blind, placebo-controlled study (Study Effisayil-1) [NCT03782792] was conducted to evaluate the clinical efficacy and safety of intravenous SPEVIGO in adult subjects with flares of generalized pustular psoriasis (GPP). Subjects were randomized if they had a flare of GPP of moderate-to-severe intensity, as defined by:
Subjects were required to discontinue systemic and topical therapy for GPP prior to receiving study drug.
A total of 53 subjects were randomized (2:1) to receive a single intravenous dose of 900 mg SPEVIGO (N=35) or placebo (N=18) (administered over 90 minutes) during the double-blind portion of the study.
The study population consisted of 32% male and 68% female. The mean age was 43 years (range: 21 to 69 years); 55% of subjects were Asian and 45% were White. For ethnicity, there were no subjects that identified as Hispanic or Latino in the study. Most subjects included in the study had a GPPPGA pustulation sub score of 3 (43%) or 4 (36%), and subjects had a GPPPGA total score of 3 (81%) or 4 (19%). In this study, 25% of subjects had been previously treated with biologic therapy for GPP. At baseline acute flare, of the subjects with white blood cell count (WBC) assessments, 45% and 31% of subjects in the intravenous SPEVIGO and placebo groups, respectively, had (WBC) >12 x 109/L. Seventeen percent and 11% of subjects in the intravenous SPEVIGO and placebo groups, respectively, had temperature >38o Celsius. Of the subjects with WBC assessments, 12% and 6% of subjects in the SPEVIGO and placebo groups, respectively, had both WBC >12 x 109/L and temperature >38° Celsius [see ADVERSE REACTIONS].
The primary endpoint of the study was the proportion of subjects with a GPPPGA pustulation sub score of 0 (indicating no visible pustules) at Week 1 after treatment.
Clinical Response
The results of the primary endpoint are presented in Table 3.
Table 3 : GPPPGA Pustulation Sub Score at Week 1 in Adult Subjects with Flares of GPP in Study Effisayil-1 (Intravenous SPEVIGO)
| Intravenous SPEVIGO (N=35) |
Placebo (N=18) |
|
| Subjects achieving a GPPPGA pustulation sub score of 0, n (%) | 19 (54) | 1 (6) |
| Risk difference versus placebo, % (95% CI) | 49 (21, 67) | |
| GPPPGA = Generalized Pustular Psoriasis Physician Global Assessment | ||
In Study Effisayil-1, subjects in either treatment group who continued to experience flare symptoms at Week 1 were eligible to receive a single open-label intravenous dose of 900 mg of SPEVIGO (second dose and first dose for subjects in the SPEVIGO and placebo groups, respectively). At Week 1, 12 (34%) subjects and 15 subjects (83%) in the intravenous SPEVIGO and placebo groups, respectively, received open-label SPEVIGO. In subjects who were randomized to intravenous SPEVIGO and received an open-label dose of SPEVIGO at Week 1, 5 (42%) subjects had a GPPPGA pustulation sub score of 0 at Week 2 (one week after their second dose of SPEVIGO).
This study did not include sufficient numbers of subjects to determine if there are differences in response according to biological sex, age, race, baseline GPPPGA pustulation sub score, and baseline GPPPGA total score.
A randomized, double-blind, placebo-controlled study (Study Effisayil-2) [NCT04399837] evaluated the efficacy and safety of SPEVIGO for subcutaneous administration in adults and pediatric subjects (12 years of age and older and weighing at least 40 kg) with a history of at least two GPP flares of moderate-to-severe intensity in the past. Subjects were randomized if they had a GPPPGA total score of 0 or 1 at screening and randomization. Subjects were required to discontinue systemic and topical therapy for GPP prior to or at randomization. These subjects must have had a history of flaring while on concomitant treatment for GPP or a history of flaring upon dose reduction or discontinuation of these concomitant medications.
A total of 123 subjects were randomized (1:1:1:1) to one of four treatment arms:
While a 600 mg LD dose of SPEVIGO followed by 300 mg every 12 weeks dosage and a 300 mg LD of SPEVIGO followed by 150 mg every 12 weeks dosage were studied in Study Effisayil-2, these dosages are not approved. The recommended dosage of SPEVIGO for treatment of GPP when not experiencing a flare is a subcutaneous LD of 600 mg followed by 300 mg subcutaneously, administered every 4 weeks [see DOSAGE AND ADMINISTRATION]. The results summarized in Table 4 are those for the recommended dosage regimen.
The study population was 38% male and 62% female. The mean age was 40 years old (range: 14 to 75 years) with 8 (7%) pediatric subjects (2 per treatment arm); 64% of subjects were Asian and 36% were White. For ethnicity, 6% of subjects identified as Hispanic or Latino. Subjects included in the study had a GPPPGA pustulation sub score of 1 (28%) or 0 (72%), and subjects had a GPPPGA total score of 1 (86%) or 0 (14%). At the time of randomization, 75% of subjects were treated with systemic therapy for GPP, which was discontinued at the start of the randomized study treatment.
Subjects who experienced a GPP flare were eligible to receive up to two open-label intravenous doses of 900 mg SPEVIGO [see DOSAGE AND ADMINISTRATION]. Two (7%) subjects in the subcutaneous SPEVIGO 600 mg LD/300 mg every 4 weeks arm and 15 (48%) subjects in the placebo arm received intravenous SPEVIGO for treatment of GPP flare.
The primary endpoint of the study was the time to the first GPP flare up to Week 48 (defined by a GPPPGA pustulation sub score of ≥ 2 and an increase in GPPPGA total score by ≥ 2 from baseline). The key secondary endpoint was the occurrence of at least one GPP flare up to Week 48.
Clinical Response
The number of subjects who experienced at least one GPP flare and the time to first GPP flare are presented in Table 4 and Figure 1.
Table 4 : Occurrence of at Least One GPP Flare up to Week 48 in Adults and Pediatric Subjects (12 Years of Age and Older and Weighing At Least 40 kg) With a History of GPP in Study Effisayil-2 (Subcutaneous SPEVIGO)
| Subcutaneous SPEVIGO 600 mg LD, followed by 300 mg every 4 weeks (N=30) |
Placebo (N=31) |
|
| Subjects with GPP flares, n (%)* | 3 (10) | 16 (52) |
| Risk difference for GPP flare occurrence vs placebo,% (95% CI) | -39 (-62, -16) | |
| *The use of intravenous SPEVIGO treatment or investigator-prescribed standard of care to treat GPP worsening were considered as onset of GPP flare | ||
Figure 1 : Time to First GPP Flare up to Week 48 in Adults and Pediatric Subjects (12 Years of Age and Older and Weighing At Least 40 kg) With a History of GPP in Study Effisayil-2 (Subcutaneous SPEVIGO)
 |
The results of the primary and key secondary endpoints were generally consistent across subgroups including biological sex, age, race, BMI, body weight, mutation status in IL36RN, concurrent plaque psoriasis, GPPPGA total score at baseline, and irrespective of any systemic GPP treatment at randomization.
SPEVIGO®
(spea VEE go)
(spesolimab-sbzo) injection, for subcutaneous or intravenous use
What is the most important information I should know about SPEVIGO?
SPEVIGO may cause serious side effects, including:
Tell your healthcare provider or get emergency medical help right away if you or your child get any of the following symptoms during or after your or your child’s SPEVIGO injection:
See “What are the possible side effects of SPEVIGO?” for more information about side effects.
What is SPEVIGO?
SPEVIGO is a prescription medicine used to treat generalized pustular psoriasis (GPP) in adults and children 12 years of age and older who weigh at least 88 pounds (40 kg).
It is not known if SPEVIGO is safe and effective in children under 12 years of age or who weigh less than 88 pounds (40 kg).
Do not receive SPEVIGO if you or your child have had a severe or life-threatening allergic reaction to spesolimabsbzo or any of the ingredients in SPEVIGO. See the end of this Medication Guide for a complete list of ingredients in SPEVIGO.
Before you or your child receive SPEVIGO, tell your healthcare provider about all of your medical conditions, including if you or your child:
Tell your healthcare provider about all the medicines you or your child take, including prescription and over-thecounter medicines, vitamins, and herbal supplements.
How will I receive SPEVIGO?
When given under the skin (subcutaneously) for treatment of GPP when not experiencing a flare:
When given in a vein (intravenously) for GPP flare treatment:
What are the possible side effects of SPEVIGO?
SPEVIGO may cause serious side effects. See “What is the most important information I should know about SPEVIGO?”
The most common side effects of SPEVIGO for GPP flare treatment include:
The most common side effects of SPEVIGO for treatment of GPP when not experiencing a flare include:
These are not all of the possible side effects of SPEVIGO.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store SPEVIGO?
Keep SPEVIGO and all medicines out of the reach of children.
General information about the safe and effective use of SPEVIGO.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use SPEVIGO for a condition for which it was not prescribed. Do not give SPEVIGO to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about SPEVIGO that is written for health professionals.
What are the ingredients in SPEVIGO?
Active ingredient: spesolimab-sbzo
Inactive ingredients: arginine hydrochloride, glacial acetic acid, polysorbate 20, sodium acetate, sucrose, and Water for Injection
INSTRUCTIONS
SPEVIGO®
(spea VEE go)
(spesolimab-sbzo) injection, for subcutaneous use
This Instructions for Use contains information on how to inject SPEVIGO.
Read both sides of this Instructions for Use before you use SPEVIGO for the first time and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your or your child’s medical condition or treatment. Your healthcare provider should show you or your child the right way to inject SPEVIGO before you try to inject yourself or your child for the first time. In children 12 to 17 years of age, SPEVIGO should be given under supervision of an adult.
SPEVIGO comes in a prefilled syringe with a safety cover.
SPEVIGO is for one-time use only. Do not reuse the prefilled syringes.
Your healthcare provider has prescribed a dose of SPEVIGO for you or your child that requires 2 injections (2 prefilled syringes) to deliver a complete dose. You must inject the contents of both SPEVIGO prefilled syringes that come in the carton to deliver the complete dose.
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Getting to know SPEVIGO:
SPEVIGO comes in a prefilled syringe with a safety cover. The needle is pulled back into the safety cover after injection.
Guide to parts:
The figure below shows SPEVIGO before use, and after use with the activated safety cover.
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Important information you need to know before injecting SPEVIGO:
Storing SPEVIGO:
Keep SPEVIGO and all medicines out of the reach of children.
Step 1
Gather supplies
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Step 2
Preparing to inject SPEVIGO
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Step 3
Inspecting the prefilled syringes
Check both prefilled syringes now:
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Preparing for your first injection
Prepare for the first of 2 injections.
You will repeat the following steps with the second syringe right away after your first injection.
2 injections are needed for a complete dose.
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Step 4
Choosing the injection site
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Step 5
Clean the injection site
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Step 6
Removing the cap from the prefilled syringe
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Step 7
Pinch the skin
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Step 8
Injecting SPEVIGO
Inserting the needle:
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Injecting the medicine:
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Checking injection is complete:
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Important: Do not move the prefilled syringe when inserting the needle into your skin, while injecting, or when removing the needle from your skin.
Step 9
Second injection
Important:You must inject the contents of both SPEVIGO prefilled syringes to give a complete dose.
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Step 10
Disposing of the used SPEVIGO prefilled syringes and caps
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When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: https://www.fda.gov/safesharpsdisposal.
Important: Always keep the sharps disposal container out of the reach of children.
If you have any problems with your injection, do not use another SPEVIGO prefilled syringe. Call your healthcare provider or pharmacist for help.
For more information call 1-800-542-6257.
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
