Tremfya

TREMFYA- guselkumab injection
Janssen Biotech, Inc.

1 INDICATIONS AND USAGE

1.1 Plaque Psoriasis

TREMFYA is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

1.2 Psoriatic Arthritis

TREMFYA is indicated for the treatment of adult patients with active psoriatic arthritis.

2 DOSAGE AND ADMINISTRATION

2.1 Plaque Psoriasis

TREMFYA is administered by subcutaneous injection. The recommended dose is 100 mg at Week 0, Week 4, and every 8 weeks thereafter.

2.2 Psoriatic Arthritis

TREMFYA is administered by subcutaneous injection. The recommended dose is 100 mg at Week 0, Week 4, and every 8 weeks thereafter.

TREMFYA may be administered alone or in combination with a conventional disease-modifying antirheumatic drug (cDMARD) (e.g., methotrexate).

2.3 Important Administration Instructions

Administer TREMFYA subcutaneously. Each prefilled syringe or One-Press injector is for single-dose only. Instruct patients to inject the full amount (1 mL), which provides 100 mg of TREMFYA.

Do not inject TREMFYA into areas where the skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis [see Instructions for Use].

TREMFYA is intended for use under the guidance and supervision of a physician. TREMFYA may be administered by a health care professional, or a patient may self-inject after proper training in subcutaneous injection technique.

The TREMFYA Instructions for Use contains more detailed patient instructions on the preparation and administration of TREMFYA [see Instructions for Use].

2.4 Preparation for Use of TREMFYA Prefilled Syringe or One-Press Injector

Before injection, remove TREMFYA prefilled syringe or One-Press injector from the refrigerator and allow TREMFYA to reach room temperature (30 minutes) without removing the needle cap.

Inspect TREMFYA visually for particulate matter and discoloration prior to administration. TREMFYA is a clear and colorless to light yellow solution that may contain small translucent particles. Do not use if the liquid contains large particles, is discolored or cloudy. TREMFYA does not contain preservatives; therefore, discard any unused product remaining in the prefilled syringe or One-Press injector.

3 DOSAGE FORMS AND STRENGTHS

Injection: 100 mg/mL in a single-dose prefilled syringe or single-dose One-Press patient-controlled injector.

TREMFYA is a clear and colorless to light yellow solution that may contain small translucent particles.

4 CONTRAINDICATIONS

TREMFYA is contraindicated in patients with a history of serious hypersensitivity reaction to guselkumab or to any of the excipients [see Warnings and Precautions (5.1)] .

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis, have been reported with postmarket use of TREMFYA. Some cases required hospitalization. If a serious hypersensitivity reaction occurs, discontinue TREMFYA and initiate appropriate therapy.

5.2 Infections

TREMFYA may increase the risk of infection. In clinical trials in subjects with plaque psoriasis, infections occurred in 23% of subjects in the TREMFYA group versus 21% of subjects in the placebo group through 16 weeks of treatment. Upper respiratory tract infections, gastroenteritis, tinea infections, and herpes simplex infections occurred more frequently in the TREMFYA group than in the placebo group [see Adverse Reactions (6.1)] . The rate of serious infections for the TREMFYA group and the placebo group was ≤ 0.2%. A similar risk of infection was seen in placebo-controlled trials in subjects with psoriatic arthritis. Treatment with TREMFYA should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.

In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing TREMFYA. Instruct patients to seek medical help if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection or is not responding to standard therapy, monitor the patient closely and discontinue TREMFYA until the infection resolves.

5.3 Pre-treatment Evaluation for Tuberculosis

Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with TREMFYA. Initiate treatment of latent TB prior to administering TREMFYA. In clinical trials, 105 subjects with plaque psoriasis and 71 subjects with psoriatic arthritis with latent TB who were concurrently treated with TREMFYA and appropriate TB prophylaxis did not develop active TB. Monitor patients for signs and symptoms of active TB during and after TREMFYA treatment. Consider anti-TB therapy prior to initiating TREMFYA in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Do not administer TREMFYA to patients with active TB infection.

5.4 Immunizations

Prior to initiating therapy with TREMFYA, consider completion of all age appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with TREMFYA. No data are available on the response to live or inactive vaccines.

6 ADVERSE REACTIONS

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

• Infections [see Warnings and Precautions (5.2)]
• Hypersensitivity Reactions [see Contraindications (4)and 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 practice.

Plaque Psoriasis

In clinical trials, a total of 1823 subjects with moderate-to-severe plaque psoriasis received TREMFYA. Of these, 1393 subjects were exposed to TREMFYA for at least 6 months and 728 subjects were exposed for at least 1 year.

Data from two placebo- and active-controlled trials (PsO1 and PsO2) in 1441 subjects (mean age 44 years; 70% males; 82% white) were pooled to evaluate the safety of TREMFYA (100 mg administered subcutaneously at Weeks 0 and 4, followed by every 8 weeks).

Weeks 0 to 16:

In the 16-week placebo-controlled period of the pooled clinical trials (PsO1 and PsO2), adverse events occurred in 49% of subjects in the TREMFYA group compared to 47% of subjects in the placebo group and 49% of subjects in the U.S. licensed adalimumab group. Serious adverse events occurred in 1.9% of subjects in the TREMFYA group (6.3 events per 100 subject-years of follow-up) compared to 1.4% of subjects in the placebo group (4.7 events per 100 subject-years of follow-up), and in 2.6% of subjects in U.S. licensed adalimumab group (9.9 events per 100 subject-years of follow-up).

Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the TREMFYA group than in the placebo group during the 16-week placebo-controlled period.

Table 1: Adverse Reactions Occurring in ≥1% of Subjects through Week 16 in PsO1 and PsO2

	TREMFYA * 100 mg N=823 n (%)	Adalimumab † N=196 n (%)	Placebo N=422 n (%)
* Subjects receiving 100 mg of TREMFYA at Week 0, Week 4, and every 8 weeks thereafter † U.S. licensed adalimumab ‡ Upper respiratory infections include nasopharyngitis, upper respiratory tract infection (URTI), pharyngitis, and viral URTI. § Headache includes headache and tension headache. ¶ Injection site reactions include injection site erythema, bruising, hematoma, hemorrhage, swelling, edema, pruritus, pain, discoloration, induration, inflammation, and urticaria. # Gastroenteritis includes gastroenteritis and viral gastroenteritis. Þ Tinea infections include tinea pedis, tinea cruris, tinea infection, and tinea manuum infections. ß Herpes simplex infections include oral herpes, herpes simplex, genital herpes, genital herpes simplex, and nasal herpes simplex.
Upper respiratory infections ‡	118 (14.3)	21 (10.7)	54 (12.8)
Headache §	38 (4.6)	2 (1.0)	14 (3.3)
Injection site reactions ¶	37 (4.5)	15 (7.7)	12 (2.8)
Arthralgia	22 (2.7)	4 (2.0)	9 (2.1)
Diarrhea	13 (1.6)	3 (1.5)	4 (0.9)
Gastroenteritis #	11 (1.3)	4 (2.0)	4 (0.9)
Tinea infections Þ	9 (1.1)	0	0
Herpes simplex infections ß	9 (1.1)	0	2 (0.5)

Adverse reactions that occurred in < 1% but > 0.1% of subjects in the TREMFYA group and at a higher rate than in the placebo group through Week 16 in PsO1 and PsO2 were migraine, candida infections, and urticaria.

Specific Adverse Reactions

Infections

Infections occurred in 23% of subjects in the TREMFYA group compared to 21% of subjects in the placebo group.

The most common (≥ 1%) infections were upper respiratory infections, gastroenteritis, tinea infections, and herpes simplex infections; all cases were mild to moderate in severity and did not lead to discontinuation of TREMFYA.

Elevated Liver Enzymes

Elevated liver enzymes were reported more frequently in the TREMFYA group (2.6%) than in the placebo group (1.9%). Of the 21 subjects who were reported to have elevated liver enzymes in the TREMFYA group, all events except one were mild to moderate in severity and none of the events led to discontinuation of TREMFYA.

Safety through Week 48

Through Week 48, no new adverse reactions were identified with TREMFYA use and the frequency of the adverse reactions was similar to the safety profile observed during the first 16 weeks of treatment.

Psoriatic Arthritis

TREMFYA was studied in two placebo-controlled trials in subjects with psoriatic arthritis (748 subjects on TREMFYA and 372 subjects on placebo). Of the 748 subjects who received TREMFYA, 375 subjects received TREMFYA 100 mg at Week 0, Week 4, and every 8 weeks thereafter and 373 subjects received TREMFYA 100 mg every 4 weeks. The overall safety profile observed in subjects with psoriatic arthritis treated with TREMFYA is generally consistent with the safety profile in subjects with plaque psoriasis with the addition of bronchitis and neutrophil count decreased. In the 24-week placebo-controlled period, combined across the two studies, bronchitis occurred in 1.6% of subjects in the TREMFYA q8w group and 2.9% of subjects in the TREMFYA q4w group compared to 1.1% of subjects in the placebo group. Neutrophil count decreased occurred in 0.3% of subjects in the TREMFYA q8w and 1.6% of subjects in the TREMFYA q4w group compared to 0% of subjects in the placebo group. The majority of events of neutrophil count decreased were mild, transient, not associated with infection and did not lead to discontinuation.