FDA approves label expansion, cementing TREMFYA® as the only IL‑23 inhibitor proven to help stop further joint damage

1.3 Ulcerative Colitis

TREMFYA is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis.

1.4 Crohn’s Disease

TREMFYA is indicated for the treatment of adult patients with moderately to severely active Crohn’s disease.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Evaluations and Immunizations Prior to Treatment Initiation

• Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with TREMFYA [see Warnings and Precautions (5.3)].

• For the treatment of ulcerative colitis or Crohn’s disease, obtain liver enzymes and bilirubin levels prior to initiating treatment with TREMFYA [see Warnings and Precautions (5.4)].

• For the treatment of plaque psoriasis or psoriatic arthritis, if clinically indicated, evaluate liver enzymes and bilirubin prior to initiating treatment with TREMFYA [see Warnings and Precautions (5.4)].

• Complete all age-appropriate vaccinations according to current immunization guidelines [see Warnings and Precautions (5.5)].

2.2 Recommended Dosage for Moderate-to-Severe Plaque Psoriasis

Administer TREMFYA by subcutaneous injection at Week 0, Week 4, and every 8 weeks thereafter.

Adults

The recommended dosage is 100 mg.

Pediatric Patients 6 Years of Age and Older Who Also Weigh at Least 40 kg

The recommended dosage is 100 mg.

2.3 Recommended Dosage for Active Psoriatic Arthritis

Administer TREMFYA by subcutaneous injection 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 (e.g., methotrexate).

Adults

The recommended dosage is 100 mg.

Pediatric Patients 6 Years of Age and Older Who Also Weigh at Least 40 kg The recommended dosage is 100 mg.

2.4 Recommended Dosage for Moderately to Severely Active Ulcerative Colitis and Crohn’s Disease

Adults

Induction:

The recommended induction dosage of TREMFYA is:

• 200 mg administered by intravenous infusion over at least one hour at Week 0, Week 4, and Week 8 [see Dosage and Administration (2.6)] or

• 400 mg administered by subcutaneous injection (given as two consecutive injections of 200 mg each) at Week 0, Week 4, and Week 8.

Maintenance:

The recommended maintenance dosage of TREMFYA is:

• 100 mg administered by subcutaneous injection at Week 16, and every 8 weeks thereafter, or

• 200 mg administered by subcutaneous injection at Week 12, and every 4 weeks thereafter.

Use the lowest effective recommended dosage to maintain therapeutic response.

2.5 Preparation and Administration Instructions for Subcutaneous Injection

TREMFYA is available for subcutaneous use in the following presentations: prefilled pen (TREMFYA PEN), One-Press injector, and prefilled syringes [see Dosage Forms and Strengths (3) and How Supplied/Storage and Handling (16)].

• Each prefilled pen, One-Press injector, or prefilled syringe is for one time use in one patient only. Instruct patients to inject the full amount: 100 mg or 200 mg of TREMFYA (1 mL or 2 mL, respectively).

• TREMFYA is intended for use under the guidance and supervision of a healthcare professional. After proper training in subcutaneous injection technique:

Adults

° Adults may self-inject with the TREMFYA prefilled syringe, One-Press injector, and prefilled pen.

° Inject into the front of the thighs, the lower abdomen except for the 2 inches around the navel, or the back of the upper arms (healthcare professional or caregiver only).

Pediatric Patients 6 Years of Age and Older Who Also Weigh at Least 40 kg

° Pediatric self-administration is not recommended. Administration of TREMFYA to pediatric patients with the prefilled syringe, One-Press injector and prefilled pen should be performed by a healthcare provider or by a caregiver who has received training and demonstrated proper subcutaneous injection technique.

° Inject into the front of the thighs or the lower abdomen except for the 2 inches around the navel. For the prefilled syringe only, injection can also be given in the back of the upper arms.

• Before injection, remove TREMFYA from the refrigerator and allow to reach room temperature up to 25 °C (77 °F) (30 minutes) without removing the needle cap.

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

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

• If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.

• 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 pen, One- Press injector, or prefilled syringe.

2.6 Preparation and Administration Instructions for Intravenous Infusion (Moderately to Severely Active Ulcerative Colitis and Crohn’s Disease) Preparation Instructions:

1. Withdraw and then discard 20 mL of the 0.9% Sodium Chloride Injection from

the 250 mL infusion bag which is equal to the volume of TREMFYA to be added. 2. Withdraw 20 mL of TREMFYA from the vial and add it to the 250 mL intravenous

infusion bag of 0.9% Sodium Chloride Injection for a final concentration of 0.8 mg/mL. Gently mix the diluted solution. Discard the vial with any remaining solution.

3. Visually inspect the diluted solution for particulate matter and discoloration

before infusion. Infuse the diluted solution over a period of at least one hour. 4.

Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein

binding filter (pore size 0.2 micrometer).

5. Do not infuse TREMFYA concomitantly in the same intravenous line with other medicinal products.

6. Dispose any unused medicinal product in accordance with local requirements. Administration Instructions: • TREMFYA solution for intravenous infusion must be diluted, prepared, and infused by a healthcare professional using aseptic technique. TREMFYA does

not contain preservatives. Each vial is for one time use in one patient only.

• 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 is cloudy.

Storage of Diluted Solution:

• The diluted infusion solution may be kept at room temperature up to 25 °C

(77 °F) for up to 10 hours. Storage time at room temperature begins once the

diluted solution has been prepared. The infusion should be completed within 10 hours after the dilution in the infusion bag.

• Do not freeze.
• Discard any unused portion of the infusion solution.

DOSAGE FORMS AND STRENGTHS

3 DOSAGE FORMS AND STRENGTHS

TREMFYA is a clear and colorless to light yellow solution.

Subcutaneous Injection

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

Injection: 100 mg/mL in a single-dose prefilled pen (TREMFYA PEN). Injection: 200 mg/2 mL in a single-dose prefilled pen (TREMFYA PEN).

•

• Injection: 100 mg/mL in a single-dose prefilled syringe. reaction to guselkumab or to any of the excipients • Injection: 200 mg/2 mL (100 mg/mL) in a single-dose prefilled syringe. [see Warnings and Precautions (5.1)].

Intravenous Infusion 5 WARNINGS AND PRECAUTIONS

5.1• Hypersensitivity Reactions Injection: 200 mg/20 mL (10 mg/mL) solution in a single-dose vial.

4Serious hypersensitivity reactions, including anaphylaxis, have been reported CONTRAINDICATIONS with post market use of TREMFYA. Some cases required hospitalization. If a TREMFYA is contraindicated in patients with a history of serious hypersensitivity serious hypersensitivity reaction occurs, discontinue TREMFYA and initiate appropriate therapy.

5.2 Infections

TREMFYA may increase the risk of infection [see Adverse Reactions (6.1)].

In placebo-controlled clinical trials of up to 48 weeks in subjects with ulcerative colitis and Crohn’s disease, serious infections occurred in ≤ 2% of subjects who received TREMFYA. In the 16-week placebo-controlled trials in subjects with plaque psoriasis, the rate of serious infections for the TREMFYA group and the

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placebo group was ≤ 0.2%. A similar rate of serious infections was seen in placebocontrolled trials in subjects with psoriatic arthritis. The overall rates of infections were similar between subjects in the TREMFYA groups and subjects in the placebo groups in clinical trials for all indicated populations [see Adverse Reactions (6.1)].

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 Tuberculosis

Evaluate patients for tuberculosis (TB) infection prior to initiating TREMFYA treatment. Do not administer TREMFYA to patients with active TB infection. Initiate treatment of latent TB prior to administering TREMFYA. 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. Monitor all patients for signs and symptoms of active TB during and after TREMFYA treatment.

In clinical trials, 105 subjects with plaque psoriasis, 143 subjects with psoriatic arthritis, 43 subjects with ulcerative colitis, and 36 subjects with Crohn’s disease with latent TB who were concurrently treated with TREMFYA and appropriate TB prophylaxis did not develop active TB. In clinical trials of TREMFYA in subjects with Crohn’s disease, active TB was reported in 2 subjects during treatment with TREMFYA [see Adverse Reactions (6.1)].

5.4 Hepatotoxicity

A serious adverse reaction of drug-induced liver injury was reported in a clinical trial subject with Crohn’s disease following three doses of a higher than the recommended induction regimen. This subject had peak alanine aminotransferase (ALT) of 18x the upper limit of normal (ULN), aspartate aminotransferase (AST) of 11x ULN, and total bilirubin of 2.4x ULN. TREMFYA was subsequently discontinued, and the liver test abnormalities resolved following administration of corticosteroids [see Adverse Reactions (6.1)].

In patients with ulcerative colitis or Crohn’s disease, evaluate liver enzymes and bilirubin at baseline, for at least 16 weeks of treatment, and periodically thereafter according to routine patient management.

In patients with plaque psoriasis or psoriatic arthritis, if clinically indicated, evaluate liver enzymes and bilirubin at baseline, and periodically thereafter according to routine patient management.

Consider other treatment options in patients with evidence of acute liver disease or cirrhosis. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction.

5.5 Immunizations

Avoid use of live vaccines in patients treated with TREMFYA. Medications that interact with the immune system may increase the risk of infection following administration of live vaccines. Prior to initiating therapy with TREMFYA, complete all age-appropriate vaccinations according to current immunization guidelines. No data are available on the response to live or inactivated vaccines.

6 ADVERSE REACTIONS

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

• Hypersensitivity Reactions [see Contraindications (4) and Warnings and Precautions (5.1)]

• Infections [see Warnings and Precautions (5.2)]

• Tuberculosis [see Warnings and Precautions (5.3)]

• Hepatotoxicity [see Warnings and Precautions (5.4)]

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.

Adverse Reactions in Adults with Plaque Psoriasis

In clinical trials, a total of 1823 adult 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 patient-years of follow-up) compared to 1.4% of subjects in the placebo group (4.7 events per 100 patient-years of followup), and in 2.6% of subjects in U.S. licensed adalimumab group (9.9 events per 100 patient-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 Adult Subjects with Moderate-to- Severe Plaque Psoriasis through Week 16 in Trials PsO1 and PsO2

^a Subjects receiving 100 mg of TREMFYA at Week 0, Week 4, and every 8 weeks thereafter

^bU.S. licensed adalimumab

^c Upper respiratory infections include nasopharyngitis, upper respiratory tract infection (URTI), pharyngitis, and viral URTI.

^dHeadache includes headache and tension headache.

^e Injection site reactions include injection site erythema, bruising, hematoma, hemorrhage, swelling, edema, pruritus, pain, discoloration, induration, inflammation, and urticaria.

^fGastroenteritis includes gastroenteritis and viral gastroenteritis.

^g Tinea infections include tinea pedis, tinea cruris, tinea infection, and tinea manuum infections.

^h Herpes simplex infections include oral herpes, herpes simplex, genital herpes, genital herpes simplex, and nasal herpes simplex.

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 trials 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 through 16 weeks of treatment.

The most common (≥ 1%) infections that occurred more frequently in the TREMFYA group than in the placebo group 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. The rate of serious infections for the TREMFYA group and the placebo group was ≤ 0.2%.

• 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.

Adverse Reactions in Pediatric Subjects with Plaque Psoriasis

The safety of TREMFYA was studied in one placebo- and active-controlled clinical trial (PsO5) that included 120 pediatric subjects 6 years of age and older with moderate-to-severe plaque psoriasis [see Clinical Studies (14.1)]. The safety profile observed in pediatric subjects 6 years of age and older treated with TREMFYA up to 52 weeks was consistent with the safety profile observed in adult subjects with moderate-to-severe plaque psoriasis.

Adverse Reactions in Adults with Psoriatic Arthritis

TREMFYA was studied in two placebo-controlled trials (PsA1 and PsA2) in adult 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 (q8w) thereafter and 373 subjects received TREMFYA 100 mg every 4 weeks (q4w). The overall safety profile observed in adult subjects with psoriatic arthritis treated with TREMFYA is generally consistent with the safety profile in adult 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 with 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 with 0% of subjects in the placebo group. The majority of events of neutrophil count decreased were mild, transient,

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not associated with infection and did not lead to discontinuation. A similar risk of infection and serious infections was seen in placebo-controlled trials in subjects with psoriatic arthritis as in subjects with plaque psoriasis.

TREMFYA was additionally studied in a placebo-controlled trial (PsA3) in 1054 subjects with psoriatic arthritis (668 subjects on TREMFYA and 386 subjects on placebo). Of the 668 subjects who received TREMFYA, 388 subjects received TREMFYA 100 mg at Week 0, Week 4, and q8w thereafter and 280 subjects received TREMFYA 100 mg q4w. The overall safety profile observed in subjects with psoriatic arthritis treated with TREMFYA in trial PsA3 is consistent with the safety profile observed in trials PsA1 and PsA2.

Specific Adverse Reactions

• Elevated Liver Enzymes

In the 24-week placebo-controlled period in trials PsA1, PsA2, and PsA3, elevated liver enzymes were reported more frequently in the TREMFYA q4w (6.1%) group compared with the q8w group (4.8%) and to the placebo group (2.8%). Through Week 24, all events were mild to moderate in severity and

none led to discontinuation of TREMFYA.

Adverse Reactions in Adults with Ulcerative Colitis

TREMFYA was studied up to 12 weeks in adult subjects with moderately to severely active ulcerative colitis in a randomized, double-blind, placebo-controlled induction trial (UC1) and a randomized, double-blind, placebo-controlled, induction dosefinding trial (UC3; NCT04033445). Long-term safety up to 44 weeks was evaluated in subjects who responded to induction therapy in trials UC1 or UC3 in a randomized, double-blind, placebo-controlled maintenance trial (UC2). In a randomized, doubleblind, placebo-controlled trial (UC4), subjects received subcutaneous TREMFYA at Weeks 0, 4, and 8 followed by one of two recommended subcutaneous TREMFYA [see Clinical Studies (14.3)].

dosing regimens for a total duration of up to 24 weeks

Trials UC1, UC2 and UC3 In the induction trials (UC1 and UC3), 522 subjects received at least one dose of the TREMFYA intravenous induction regimen (i.e., 200 mg at Week 0, Week 4, and Week 8). Clinical response was defined as a decrease in modified Mayo score (mMS) of ≥30% and ≥2 points from baseline with either a ≥1 decrease from baseline in rectal bleeding subscore (RBS) or RBS of 0 or 1. In the maintenance trial (UC2), subjects who achieved clinical response after 12 weeks of TREMFYA intravenous induction treatment were randomized and received either TREMFYA 100 mg every 8 weeks (with the first dose given at Week 4 of trial UC2) or TREMFYA 200 mg every 4 weeks (with the first dose given at Week 0 of trial UC2), by subcutaneous (SC)

injection for up to an additional 44 weeks. Respiratory tract infections occurred in ≥2% of subjects treated with TREMFYA and at a higher rate than placebo (8.8% TREMFYA-treated subjects vs. 7.3% placebo-treated subjects) through Week 12 in the induction trials (UC1 and UC3). Respiratory tract infections included COVID-19, influenza, nasopharyngitis, respiratory tract infection, upper respiratory tract infection, and viral respiratory

tract infection. Adverse reactions that occurred in ≥3% of subjects treated with TREMFYA and at a higher rate than placebo through Week 44 in the maintenance trial (UC2) are

shown in Table 2. Table 2: Adverse Reactions Occurring in ≥3% of Adult Subjects with Moderately

^a Subjects receiving TREMFYA 100 mg at Week 16 and every 8 weeks thereafter or TREMFYA 200 mg at Week 12 and every 4 weeks thereafter.