ICOTYDE is indicated for the treatment of moderate-to-severe plaque psoriasis in adults and pediatric patients 12 years of age and older who weigh at least 40 kg who are candidates for systemic therapy or phototherapy.

Tablets: 200 mg of icotrokinra, yellowish orange to yellowish brown, oval, film-coated tablets debossed with '200' on one side and 'JNJ' on the other side.

None.

Icotrokinra is an IL-23 receptor antagonist, in the form of a hydrochloride salt. Icotrokinra is a 13-amino acid peptide. The molecular formula for icotrokinra is C

The chemical name for icotrokinra is (4S)-4-[([4-[(2S)-2-[(2S)-2-[([(4R,7S,10S,13S,16S,19R)-19-acetamido-7-(4-acetamidobutyl)-16-(2-amino-2-oxoethyl)-13-[(1R)-1-hydroxyethyl]-3,3,20,20-tetramethyl-10-[(7-methyl-1H-indol-3-yl)methyl]6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacycloicosan-4-yl]carbonyl)amino]-3-[4-(2-aminoethoxy)phenyl]propanamido]-3-(2-naphthyl)propanamido]tetrahydro-2H-pyran-4-yl]carbonyl)amino]-5-[[(2S)-4-amino-1-[[(2S)-1-[(2-amino-2-oxoethyl)(methyl)amino]-1-oxo-3-(pyridin-3-yl)propan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-5-oxopentanoic acid.

The structural formula for icotrokinra hydrochloride is:

Icotrokinra hydrochloride is a white to almost white powder. It is freely soluble below pH 2, very slightly soluble at pH 5, practically insoluble at pH 9, and freely soluble above pH 11. The isoelectric point (pI) of the compound is 7.15.

ICOTYDE™ (icotrokinra) tablets are supplied as 200 mg film-coated tablets for oral administration. Each tablet of ICOTYDE contains 200 mg icotrokinra (equivalent to 201.6–202.8 mg of icotrokinra hydrochloride) and the following inactive ingredients: colloidal silicon dioxide, crospovidone, magnesium stearate, and silicified microcrystalline cellulose. The film coating contains the following inactive ingredients: glyceryl monocaprylocaprate, iron oxide yellow, macrogol polyvinyl alcohol graft polymer, polyvinyl alcohol partially hydrolyzed, talc, and titanium dioxide.

The efficacy of ICOTYDE was evaluated in four multi-center, randomized, double-blind, placebo and/or active comparator-controlled trials (Trial PSO-1 [NCT06143878], Trial PSO-2 [NCT06220604], Trial PSO-3 [NCT06095115], and Trial PSO-4 [NCT06095102]) that included 2500 subjects (2428 adults and 72 pediatric subjects 12 years and older who weigh at least 40 kg) with moderate-to-severe plaque psoriasis who were eligible for systemic therapy or phototherapy.

Trial PSO-1 and Trial PSO-2 enrolled 1505 adults with moderate-to-severe plaque psoriasis defined as Investigator's Global Assessment (IGA) score ≥3, a Psoriasis Area and Severity Index (PASI) score ≥12, and body surface area (BSA) involvement ≥10%.

Subjects were randomized to either ICOTYDE 200 mg orally once daily, deucravacitinib 6 mg orally once daily or placebo. At Week 16, subjects originally randomized to placebo received ICOTYDE 200 mg orally once daily thereafter. At Week 24, subjects originally randomized to deucravacitinib received ICOTYDE 200 mg orally once daily thereafter.

Baseline characteristics were consistent across both trials. In Trial PSO-1 and Trial PSO-2, 68% of subjects were male, 78% of subjects were White, 2% of subjects were Black, and 18% of subjects were Asian; for ethnicity, 16% identified as Hispanic or Latino. The mean age was 46 (range: 18 to 86) years, and the mean baseline weight was 88 kg. At baseline, subjects had a median affected BSA of 21%, a median PASI score of 18, and 14% had a history of psoriatic arthritis. The proportion of subjects with a baseline IGA score of 4 (severe) was 20%. At baseline, 72% had received prior systemic therapy, 33% of subjects had received prior phototherapy, and 26% had received prior biologic therapy.

Trial PSO-1 and Trial PSO-2 assessed responses at Week 16 for ICOTYDE compared to placebo for two co-primary endpoints:

Other evaluated outcomes for ICOTYDE compared to placebo included IGA 0, PASI 75, PASI 100, Psoriasis Symptoms and Signs Diary (PSSD) Symptom Score of 0, and PSSD Itch Score improvement from baseline (≥4-point reduction).

Other comparisons between ICOTYDE and deucravacitinib that were secondary endpoints included:

Tables 2 and 3 present the efficacy results in adults with moderate-to-severe plaque psoriasis for Trial PSO-1 and Trial PSO-2.

Trial PSO-3 enrolled 684 subjects (618 adults and 66 pediatric subjects 12 years of age and older who weigh at least 40 kg) with moderate-to-severe plaque psoriasis defined as Investigator's Global Assessment (IGA) score ≥3, a Psoriasis Area and Severity Index (PASI) score ≥12, and BSA ≥10%.

Subjects were randomized to receive either ICOTYDE (200 mg orally once daily) or placebo for 16 weeks.

In Trial PSO-3, 65% of subjects were male, 72% of the subjects were White, 1% of the subjects were Black, and 24% of subjects were Asian; for ethnicity, 13% identified as Hispanic or Latino. The mean age was 43 (range: 12 to 85) years, the mean baseline weight was 86 kg, and 10% were 12 years to less than 18 years of age. At baseline, subjects had a median affected BSA of 20%, a median PASI score of 17, and 13% had a history of psoriatic arthritis. The proportion of subjects with a baseline IGA score of 4 (severe) was 25%. At baseline, 72% had prior systemic treatment, 30% of subjects had received prior phototherapy, and 34% had received prior biologic therapy.

Trial PSO-3 assessed responses at Week 16 for ICOTYDE compared to placebo for two co-primary endpoints:

Other evaluated outcomes for ICOTYDE compared to placebo included IGA 0, PASI 75, PASI 100, PSSD Symptom Score of 0, and PSSD Itch Score improvement from baseline (≥4-point reduction).

Table 4 presents the efficacy results in adults and pediatric subjects 12 years of age and older for Trial PSO-3.

In Trial PSO-3, adults who were randomized to ICOTYDE 200 mg orally once daily and were PASI 75 responders or IGA 0 or 1 responders at Week 24 were re-randomized to continue ICOTYDE 200 mg orally once daily or withdrawn from therapy (i.e., received placebo).

For adults who were re-randomized and had a PASI 90 response at Week 24, 84% (108/128) of subjects who continued on ICOTYDE maintained PASI 90 response at Week 52 compared to 21% (27/129) of subjects randomized to placebo. For PASI 90 responders at Week 24 who were re-randomized to placebo, the median time to loss of PASI 90 response was approximately 10 weeks.

For adults who were re-randomized and had an IGA 0/1 response at Week 24, 82% (123/150) of subjects who continued on ICOTYDE maintained IGA 0/1 response at Week 52 compared to 23% (35/150) of subjects randomized to placebo. For IGA 0/1 responders at Week 24 who were re-randomized to placebo, the median time to loss of IGA 0/1 response was approximately 10 weeks.

Trial PSO-3 included 66 pediatric subjects 12 years of age and older who weigh at least 40 kg.

Table 5 presents the efficacy results in pediatric subjects 12 years of age and older at Week 16 enrolled in Trial PSO-3.

Trial PSO-4 enrolled 311 subjects (305 adults and 6 pediatric subjects 12 years of age and older who weigh at least 40 kg) with moderate-to-severe plaque psoriasis who had a minimum BSA involvement of ≥1%, an IGA score of ≥2 and had failed to respond to at least one topical therapy for the treatment of plaque psoriasis. Additionally, subjects in Trial PSO-4 had at least one of the following baseline conditions: ss-IGA score ≥3 (at least moderate plaque psoriasis of the scalp), static Physician's Global Assessment of Genitalia (sPGA-G) score ≥3 (at least moderate plaque psoriasis of the genital area), and/or Physician's Global Assessment of Hands and/or Feet (hf-PGA) score ≥3 (at least moderate plaque psoriasis of the hands and/or feet).

Subjects were randomized to receive either ICOTYDE 200 mg orally once daily or placebo for 16 weeks. At Week 16, subjects originally randomized to placebo switched to receive ICOTYDE 200 mg orally once daily, and subjects randomized to ICOTYDE at baseline remained on treatment through the end of study.

In Trial PSO-4, 64% of subjects were male, 78% of subjects were White, 1% of subjects were Black, and 20% of subjects were Asian; for ethnicity, 7% identified as Hispanic or Latino. The mean age was 45 (range: 12 to 87) years, the mean baseline weight was 86 kg, and 2% were 12 years to less than 18 years of age. The proportion of subjects with affected BSA less than 10% was 36% with a median affected BSA of 12%. Subjects had a median PASI score of 14, and 16% had a history of psoriatic arthritis. The proportion of subjects with a baseline IGA score of 3 (moderate), and 4 (severe) were 73% and 22%, respectively. The proportion of subjects with ss-IGA score of 3 or greater was 81%. The proportion of subjects with sPGA-G score of 3 or greater was 45%. The proportion of subjects with hf-PGA score of 3 or greater was 23%. Scalp, genital and hand/foot subpopulations were not mutually exclusive. At baseline, 73% had received prior systemic therapy, 39% of subjects had received prior phototherapy, and 33% had received prior biologic therapy.

In Trial PSO-4, the primary endpoint was the proportion of subjects who achieved an IGA 0/1 response (defined as IGA score of 0 [cleared] or 1 [minimal] and a ≥2-grade improvement from baseline at Week 16).

Other secondary endpoints at Week 16 included proportion of subjects who achieved ss-IGA score of 0 (absence of disease) or 1 (very mild disease), Psoriasis Scalp Severity Index (PSSI) 90, improvement in scalp itch as measured by Scalp Itch Numerical Rating Scale (NRS) Score, sPGA-G score of 0 (clear) or 1 (minimal), improvement of genital itch severity as measured by a reduction of at least 4 points in the 11-point Genital Psoriasis Symptoms Scale (GPSS) Genital Itch NRS Score, and the patient-perceived impact of psoriasis of the genital area on limiting frequency of sexual activity (intercourse or other activities) as measured by the Genital Psoriasis Sexual Frequency Questionnaire (GenPs-SFQ) Item 2.

Table 6 presents the efficacy results in adults and pediatric subjects 12 years of age and older at Week 16 for Trial PSO-4.

An examination of age, gender, race, body weight, baseline disease severity, and previous treatment with systemic or biologic agents did not identify differences in response to ICOTYDE among these subgroups.

ICOTYDE™ (icotrokinra) tablets: 200 mg, yellowish orange to yellowish brown, oval, film-coated tablets debossed with '200' on one side and 'JNJ' on the other side.

ICOTYDE is supplied in bottles of 30 tablets (NDC Number: 57894-201-30), with a silica gel desiccant and a child-resistant closure.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Instruct patients of the importance of communicating any history of infections to the healthcare provider and contacting their healthcare provider if they develop any symptoms of an infection

Advise patients to contact their healthcare provider if they experience symptoms suggestive of TB (e.g., unexplained fever, cough, or difficulty breathing)

Instruct patients to inform their healthcare provider that they are taking ICOTYDE prior to a potential vaccination

Instruct patients to take ICOTYDE once daily upon waking on an empty stomach with water. Instruct patients to wait at least 30 minutes after taking ICOTYDE before eating food

Instruct patients who have trouble swallowing tablets to disperse the tablet in water

Advise pregnant women that there is a pregnancy safety study that monitors pregnancy outcomes in women exposed to ICOTYDE during pregnancy, and they can be enrolled by calling 1-800-526-7736 or www.ICOTYDE.com

Rx only

NDC 57894-201-30

ICOTYDE™

200 mg

oral use

Attention: Dispense the enclosed

30 film-coated tablets

Johnson