SPEVIGO

SPEVIGO- spesolimab injection
Boehringer Ingelheim Pharmaceuticals, Inc.

1 INDICATIONS AND USAGE

SPEVIGO is indicated for the treatment of generalized pustular psoriasis (GPP) flares in adults.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dose

Administer SPEVIGO as a single 900 mg dose 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.

2.2 Preparation and Administration Instructions

SPEVIGO must be diluted before use.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permits. SPEVIGO is a colorless to slightly brownish-yellow, clear to slightly opalescent solution. Discard the vial if the solution is cloudy, discolored, or contains large or colored particulates.

Preparation

• Use aseptic technique to prepare the solution for infusion.
• Draw and discard 15 mL from a 100 mL container of sterile 0.9% Sodium Chloride Injection.
• Slowly replace with 15 mL of SPEVIGO (complete content from two vials of 450 mg/7.5 mL).
• Mix gently before use.
• Use the diluted SPEVIGO solution immediately.

Administration

• Do not mix SPEVIGO with other medicinal products.
• Administer SPEVIGO as a continuous intravenous infusion through an intravenous line containing a sterile, non-pyrogenic, low protein binding in-line filter (pore size of 0.2 micron) over 90 minutes.
• If the infusion is slowed or temporarily stopped, the total infusion time (including stop time) should not exceed 180 minutes [see Warnings and Precautions (5.3)].
• A pre-existing intravenous line may be used for administration of SPEVIGO. The line must be flushed with sterile 0.9% Sodium Chloride Injection prior to and at the end of infusion. No other infusion should be administered in parallel via the same intravenous access.
• No incompatibilities have been observed between SPEVIGO and infusion sets composed of polyvinylchloride (PVC), polyethylene (PE), polypropylene (PP), polybutadiene and polyurethane (PUR), and in-line filter membranes composed of polyethersulfone (PES, neutral and positively charged) and positively charged polyamide (PA).

Storage of Diluted Solution

If not administered immediately, refrigerate the diluted solution at 2°C to 8°C (36°F to 46°F) for no more than 4 hours. Protect from light.

2.3 Testing and Procedures Prior to Treatment Initiation

Evaluate patients for 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 (5.2)].

3 DOSAGE FORMS AND STRENGTHS

SPEVIGO is a sterile, preservative-free, colorless to slightly brownish-yellow, clear to slightly opalescent solution.

Injection: 450 mg/7.5 mL (60 mg/mL) solution in a single-dose vial

4 CONTRAINDICATIONS

SPEVIGO is contraindicated in patients with severe or life-threatening hypersensitivity to spesolimab-sbzo or to any of the excipients in SPEVIGO. Reactions have included drug reaction with eosinophilia and systemic symptoms (DRESS) [see Warnings and Precautions (5.3) and Adverse Reactions (6.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Infections

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 (6.1)].

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 for use 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 after treatment with SPEVIGO.

5.2 Risk of Tuberculosis

Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with SPEVIGO. Do not administer SPEVIGO to 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.

5.3 Hypersensitivity and Infusion-Related Reactions

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 spesolimab-sbzo in subjects with GPP [see Adverse Reactions (6.1)].

If a patient develops signs of anaphylaxis or other serious hypersensitivity, discontinue SPEVIGO immediately and initiate appropriate treatment [see Contraindications (4)].

If a patient develops mild or moderate 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.

5.4 Vaccinations

Avoid use of live vaccines in patients treated with SPEVIGO. No specific studies have been conducted in SPEVIGO-treated patients who have recently received live viral or live bacterial vaccines.

6 ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Infections [see Warnings and Precautions (5.1)]

6.1 Clinical Trials Experience

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 trial comparing a single intravenous 900 mg dose of SPEVIGO (n=35) with placebo (n=18) in subjects with generalized pustular psoriasis 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 (14)].

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 SPEVIGO group than in the placebo group through Week 1.

Table 1 Selected Adverse Reactions Occurring in ≥1% of the SPEVIGO Group and More Frequently than in the Placebo Group through Week 1 (Study Effisayil-1)

Adverse Reaction	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

Specific Adverse Reactions

Infections

The most frequent adverse reactions that occurred in subjects treated with 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%).

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Two cases of DRESS were reported in Study Effisayil-1 in subjects with GPP who were treated with spesolimab-sbzo. 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”.

Safety through Week 12 and 17

In Study Effisayil-1, additional adverse reactions that occurred through Week 12 in subjects treated with 1 single 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 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%), and 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 dose of open-label rescue SPEVIGO from Week 1 to Week 12 (range 1-3 total doses).

Clinical Development

Guillain-Barre syndrome

Among approximately 750 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 trials for unapproved indications.

Injection Site Reactions

During clinical development, injection site reactions (including injection site erythema, injection site swelling, injection site pain, injection site induration, and injection site warmth) occurred with spesolimab-sbzo.