SOTYKTU 6mg tablets medication leaflet

SOTYKTU 6 mg film-coated tablets

Each film-coated tablet contains 6 mg of deucravacitinib.

Each film-coated tablet contains 44 mg of lactose (see section 4.4).

For the full list of excipients, see section 6.1.

Film-coated tablet (tablet)

Pink, round, biconvex, film-coated tablet of 8 mm diameter, printed with “BMS 895”, and “6 mg” onone side in two lines, plain on the other side.

SOTYKTU is indicated for the treatment of moderate to severe plaque psoriasis in adults who arecandidates for systemic therapy.

Treatment should be initiated under the guidance and supervision of a physician experienced in thediagnosis and treatment of psoriasis.

The recommended dose is 6 mg taken orally once daily.

If a patient shows no evidence of therapeutic benefit after 24 weeks, treatment discontinuation shouldbe considered. The patient's response to treatment should be evaluated on a regular basis.

No dose adjustment is required in elderly patients aged 65 years and older (see section 5.2). Clinicalexperience in patients ≥ 75 years is very limited and deucravacitinib should be used with caution inthis group of patients.

No dose adjustment is required in patients with renal impairment, including end stage renal disease(ESRD) patients on dialysis (see section 5.2).

No dose adjustment is required in patients with mild or moderate hepatic impairment. Deucravacitinibis not recommended to be used in patients with severe hepatic impairment (see section 5.2).

The safety and efficacy of deucravacitinib in children and adolescents below the age of 18 years havenot yet been established. No data are available.

For oral use.

Tablets can be taken with or without food. Tablets should be swallowed whole and should not becrushed, cut, or chewed.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Clinically important active infections (e.g. active tuberculosis, see section 4.4).

Deucravacitinib may increase the risk of infections (see section 4.8).

Treatment with deucravacitinib should not be initiated in patients with any clinically important activeinfection until the infection resolves or is adequately treated (see section 4.3). Caution should beexercised when considering the use of deucravacitinib in patients with a chronic infection or a historyof recurrent infection.

Patients treated with deucravacitinib should be instructed to seek medical advice if signs or symptomssuggestive of an infection occur. If a patient develops a clinically important infection or is notresponding to standard therapy, the patient should be monitored carefully and deucravacitinib shouldnot be given until the infection resolves.

Pre-treatment evaluation for tuberculosis

Prior to initiating treatment with deucravacitinib, patients should be evaluated for tuberculosis (TB)infection. Deucravacitinib should not be given to patients with active TB (see section 4.3). Treatmentof latent TB should be initiated prior to administering deucravacitinib. Anti-TB therapy should beconsidered prior to initiation of deucravacitinib in patients with a past history of latent or active TB inwhom an adequate course of treatment cannot be confirmed. Patients receiving deucravacitinib shouldbe monitored for signs and symptoms of active TB.

Malignancies, including lymphomas and non-melanoma skin cancer (NMSC), were observed inclinical studies with deucravacitinib.

It is not known whether tyrosine kinase 2 (TYK2) inhibition may be associated with the adversereactions of Janus Kinase (JAK) inhibition. In a large randomised active controlled study of a JAKinhibitor in rheumatoid arthritis (RA) patients 50 years and older with at least one additionalcardiovascular risk factor, a higher rate of malignancies, particularly lung cancer, lymphoma and

NMSC, was observed with a JAK inhibitor compared to tumour necrosis factor (TNF) inhibitors.

Limited clinical data are available to assess the potential relationship of exposure to deucravacitiniband the development of malignancies. Long-term safety evaluations are ongoing. The risks andbenefits of deucravacitinib treatment should be considered prior to initiating patients.

Major adverse cardiovascular events (MACE), deep venous thrombosis (DVT) and pulmonaryembolism (PE)

It is not known whether TYK2 inhibition may be associated with the adverse reactions of JAKinhibition. In a large randomised active-controlled study of a JAK inhibitor in RA patients 50 yearsand older with at least one additional cardiovascular risk factor, a higher rate of MACE, defined ascardiovascular death, non-fatal myocardial infarction and non-fatal stroke, and a dose dependenthigher rate of venous thromboembolism including DVT and PE were observed with a JAK inhibitorcompared to TNF inhibitors.

An increased risk of MACE, DVT and PE was not observed in clinical trials with deucravacitinib.

Long-term safety evaluations for deucravacitinib are ongoing. The risks and benefits ofdeucravacitinib treatment should be considered prior to initiating patients.

Prior to initiating therapy with deucravacitinib, consider completion of all age-appropriateimmunisations according to current immunisation guidelines. Use of live vaccines in patients beingtreated with deucravacitinib should be avoided. The response to live or non-live vaccines has not beenevaluated.

This medicinal product contains lactose. Patients with rare hereditary problems of galactoseintolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinalproduct.

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially‘sodium-free’.

Clinical studies indicate that deucravacitinib does not have clinically relevant drug interactions uponcoadministration with the following other medicinal products and therefore no dose adjustments areneeded.

Effect of deucravacitinib on other medicinal products

Deucravacitinib does not meaningfully impact plasma exposures of rosuvastatin (BCRP and OATPsubstrate), methotrexate (substrate of BCRP and renal transporters), mycophenolate mofetil (MMF)(CES1 and CES2 substrate), or oral contraceptives (norethindrone acetate and ethinyl estradiol).

Effect of other medicinal products on deucravacitinib

Medicinal products that are inhibitors or inducers of CYP enzymes or transporters such ascyclosporine (dual P-gp/breast cancer resistance protein [BCRP] inhibitor), fluvoxamine (strong

CYP 1A2 inhibitor), ritonavir (moderate CYP 1A2 inducer), diflunisal (UGT 1A9 inhibitor),pyrimethamine (OCT1 inhibitor), famotidine (H2 receptor antagonist) or rabeprazole (proton pumpinhibitor) do not meaningfully affect plasma deucravacitinib exposures (see section 5.2).

There is a limited amount of data on the use of deucravacitinib in pregnant women. Animal studies donot indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). Asa precautionary measure, it is preferable to avoid the use of deucravacitinib during pregnancy.

It is unknown whether deucravacitinib/metabolites are excreted in human milk.

Available data in animals have shown excretion of deucravacitinib in milk (see section 5.3).

A risk to the newborns/infants by breast-feeding cannot be excluded. A decision must be madewhether to discontinue breast-feeding or to discontinue/abstain from deucravacitinib therapy takinginto account the benefit of breast feeding for the child and the benefit of therapy for the woman.

The effect of deucravacitinib on human fertility has not been evaluated. Animal studies do not indicatedirect or indirect harmful effects with respect to fertility (see section 5.3).

Deucravacitinib has no or negligible influence on the ability to drive and use machines.

The most commonly reported adverse reaction is upper respiratory infections (18.9%), most frequentlynasopharyngitis. The longer-term safety profile of deucravacitinib was similar and consistent withprevious experience.

The following list of adverse reactions for deucravacitinib is from clinical trials in plaque psoriasis(Table 1). These reactions are presented by MedDRA System Organ Class and by frequency.

Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10);uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known(cannot be estimated from the available data).

Table 1: List of adverse reactions

System Organ Class Frequency Adverse reaction

Infections and infestations Very common Upper respiratory infectionsa

Common Herpes simplex infectionsb

Uncommon Herpes zoster

Gastrointestinal disorders Common Oral ulcersc

Skin and subcutaneous tissue disorders Common Acneiform rashd

Folliculitis

Investigations Common Blood creatine phosphokinase increaseda Upper respiratory infections include nasopharyngitis, upper respiratory tract infection, viral upperrespiratory tract infection, pharyngitis, sinusitis, acute sinusitis, rhinitis, tonsillitis, peritonsillar abscess,laryngitis, tracheitis, and rhinotracheitis.b Herpes simplex infections include oral herpes, herpes simplex, genital herpes, and herpes viral infection.c Oral ulcers include aphthous ulcer, mouth ulceration, tongue ulceration, and stomatitis.d Acneiform rash includes acne, dermatitis acneiform, rash, rosacea, pustule, rash pustular, and papule.

In POETYK PSO-1 and POETYK PSO-2 (see section 5.1), infections occurred in 29.1% of patients inthe deucravacitinib group (116.0 events per 100 person-years) compared to 21.5% of patients in theplacebo group (83.7 events per 100 person-years) during the first 16 weeks. The majority of infectionswere non-serious and mild to moderate in severity and did not lead to discontinuation ofdeucravacitinib. The incidence of serious infections in the deucravacitinib group was 0.6% (2.0 eventsper 100 person-years) and in the placebo group was 0.5% (1.6 events per 100 person-years).

The rate of infections in the deucravacitinib group did not increase through week 52 (95.4 events per100 person-years). The rate of serious infections in the deucravacitinib group did not increase throughweek 52 (1.7 events per 100 person-years).

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

Deucravacitinib has been administered in healthy subjects as single doses up to 40 mg (>6 times therecommended human dose of 6 mg/day) and in multiple doses up to 24 mg/day (12 mg twice daily) for14 days without dose-limiting toxicity.

In case of overdose, it is recommended that the patient be monitored for any signs or symptoms ofadverse reactions and appropriate symptomatic treatment instituted immediately. Dialysis does notsubstantially clear deucravacitinib from systemic circulation (see section 5.2).

Pharmacotherapeutic group: Immunosuppressants, ATC code: L04AF07

Deucravacitinib selectively inhibits the TYK2 enzyme (TYK2 belongs to the JAK family).

Deucravacitinib binds to the regulatory domain of TYK2, stabilizing an inhibitory interaction betweenthe regulatory and the catalytic domains of the enzyme. This results in allosteric inhibition of receptor-mediated activation of TYK2 and its downstream functions in cells. TYK2 mediates signalling ofinterleukin-23 (IL-23), interleukin-12 (IL-12), and type I interferons (IFN), which are naturallyoccurring cytokines involved in inflammatory and immune responses. Deucravacitinib inhibits therelease of proinflammatory cytokines and chemokines.

In patients with psoriasis, deucravacitinib reduced psoriasis associated gene expression in psoriaticskin including reductions in IL-23-pathway and type I IFN pathway regulated genes. Deucravacitinibreduced IL-17A, IL-19 and β-defensin by 47-50%, 72% and 81-84%, respectively following 16 weeksof once daily treatment.

The efficacy and safety of deucravacitinib were assessed in two multicentre, randomised,double-blind, placebo- and apremilast-controlled clinical studies (POETYK PSO-1 and POETYK

PSO-2) in patients who were 18 years of age and older with moderate-to-severe plaque psoriasis andwere eligible for systemic therapy or phototherapy. Patients had body surface area (BSA) involvementof ≥ 10%, a Psoriasis Area and Severity Index (PASI) score ≥ 12, and a static Physician’s Global

Assessment (sPGA) ≥ 3 (moderate or severe) on a 5-point scale of overall disease severity.

POETYK PSO-1 and POETYK PSO-2 evaluated a total of 1686 patients with 843 randomised todeucravacitinib 6 mg once daily, 422 to apremilast 30 mg twice daily, and 421 to placebo.

In both studies, patients receiving placebo switched to deucravacitinib at week 16, which continued upto week 52. Patients randomised to apremilast who did not achieve a PASI 50 (POETYK PSO-1) or

PASI 75 (POETYK PSO-2) response at week 24 switched to deucravacitinib, and continued up toweek 52. In POETYK PSO-1 patients who were randomised to deucravacitinib continued treatmentup to week 52. In POETYK PSO-2, deucravacitinib treated patients who achieved PASI 75 at week 24were re-randomised 1:1 to continue deucravacitinib (maintenance) or were switched to placebo(withdrawal).

Baseline disease characteristics were consistent for the study population in both studies: the majority ofpatients were male (67%), mean age was approximately 47 years old with the majority of patientsbetween 40 and 64 years of age. 10% of patients were ≥ 65 years of age. The overall median PASIscore was 18.7, and median BSA was 20%. Baseline sPGA score was 3 (moderate) in 79.8% ofpatients and 4 (severe) in 20.2%. Median Dermatology Life Quality Index (DLQI) score was 11. A totalof 18.4% of study patients had a history of psoriatic arthritis.

Across both studies, 40% of patients had received prior phototherapy, 42.4% were naive to anysystemic therapy (including biologic and/or non-biologic treatment), 41% received prior non-biologicsystemic treatment, and 34.8% had received prior biologic therapy (16.1% TNF, 4.9% IL-12/23,16.6% IL-17 and 4.4% IL-23 inhibitors).

The co-primary endpoints in the two studies were the proportions of patients who achieved 1) at leasta 75% improvement in PASI scores (PASI 75) from baseline and 2) a sPGA score of clear or almostclear (0 or 1) at week 16 versus placebo.

In study POETYK PSO-1, PASI 75 was achieved with deucravacitinib in 58.4%, with apremilast in35.1% and with placebo in 12.7% of the patients at week 16. Static Physician’s Global Assessment(sPGA) of clear or almost clear at week 16 was achieved in 53.6%, 32.1% and 7.2% of the patients inthe deucravacitinib, apremilast and placebo groups respectively. For these co-primary endpointssuperiority of deucravacitinib to placebo was demonstrated. Consistent results were seen in study

POETYK PSO-2.

Table 2 presents the main efficacy results for the co-primary and other endpoints.

Table 2: Main efficacy results in adults with plaque psoriasis

POETYK PSO-1 POETYK PSO-2

Deucravacitinib Apremilast Placebo Deucravacitinib Apremilast Placebo

Endpoint (N = 332) (N = 168) (N = 166) (N = 511) (N = 254) (N = 255)n (%) n (%) n (%) n (%) n (%) n (%)sPGA 0/1

Week 16 178 (53.6) 54 (32.1)d 12 (7.2)a,d 253 (49.5) 86 (33.9)d 22 (8.6)a,d

Week 24 195 (58.7) 52 (31.0)d - 251 (49.8)b 75 (29.5)d -sPGA 0

Week 16 58 (17.5) 8 (4.8)d 1 (0.6)d 80 (15.7) 16 (6.3)e 3 (1.2)d

PASI 75

Week 16 194(58.4) 59 (35.1)d 21 (12.7)a,d 271 (53.0) 101 (39.8)e 24 (9.4)a,d

Week 24 230 (69.3) 64 (38.1)d - 296 (58.7)b 96 (37.8)d -

PASI 90

Week 16 118 (35.5) 33 (19.6)e 7 (4.2)d 138 (27.0) 46 (18.1)f 7 (2.7)d

Week 24 140 (42.2) 37 (22.0)d - 164 (32.5)b 50 (19.7)d -

PASI 100

Week 16 47 (14.2) 5 (3.0)d 1 (0.6)d 52 (10.2) 11 (4.3)f 3 (1.2)d

Scalp

Specific (N = 209) (N = 110) (N = 121) (N = 305) (N = 166) (N = 173)

PGA 0/1c

Week 16 147 (70.3) 43 (39.1)d 21 (17.4)d 182 (59.7) 61 (36.7)d 30 (17.3)d

Non-responder imputation (NRI) was used; patients who discontinued treatment or the study prior to theendpoint or had missing data were counted as non-responders.a Co-primary endpoint comparing deucravacitinib with placebob N = 504 accounting for missed assessments due to COVID-19 pandemicc Includes patients with baseline Scalp Specific PGA score of ≥ 3d p ≤ 0.0001 for comparison between deucravacitinib and placebo or deucravacitinib and apremilaste p < 0.001 for comparison between deucravacitinib and apremilastf p < 0.01 for comparison between deucravacitinib and apremilast

Examination of age, gender, race, body weight, duration of disease, baseline disease severity, andprevious treatment with biologic or non-biologic agents did not identify differences in response todeucravacitinib among these subgroups.

Response over time

Deucravacitinib showed rapid onset of efficacy with maximum PASI 75 response achieved byweek 24 (POETYK PSO-1 and PSO-2) and maintained through week 52 (POETYK PSO-1) (see

Figure 1).

Figure 1: PASI 75 response (NRI) through week 52 by visit in POETYK PSO-1deucravacitinib, n = 332apremilast, n = 168placebo, n = 166

Week

Percent of Patients (%)

Maintenance and durability of response

In POETYK PSO-2, to evaluate maintenance and durability of response, patients who were originallyrandomised to deucravacitinib and achieved PASI 75 response at week 24, were re-randomised toeither continue treatment on deucravacitinib or receive placebo. For responders at week 24 who werere-randomised to placebo, the median time to loss of PASI 75 response was approximately 12 weeks.

Figure 2 shows the PASI 75 responses in the two arms from week 24-52.

Figure 2: PASI 75 response (NRI) after re-randomisation at week-24 in POETYK PSO-2deucravacitinib, n = 148placebo, n = 150

Week

Significantly greater improvements in health-related quality of life as measured by Dermatology Life

Quality Index (DLQI) and in patient reported psoriasis symptoms (itch, pain, burning, stinging, andskin tightness) and signs (skin dryness, cracking, scaling, shedding or flaking, redness, and bleeding)as measured by the Psoriasis Symptoms and Signs Diary (PSSD) were observed in deucravacitinib-treated patients compared to placebo at week 16 and to apremilast at week 16 and week 24.

Improvement of these responses in patients receiving continuous deucravacitinib treatment weremaintained through week 52 in POETYK PSO-1.

Table 3: Patient reported outcomes in POETYK PSO-1 and POETYK PSO-2

POETYK PSO-1 POETYK PSO-2

Deucravacitinib Apremilast Placebo Deucravacitinib Apremilast Placebo

DLQI

Patients achieving 0 or 1 N = 322 N = 161 N = 160 N = 495 N = 247 N = 246(NRI)*

Week 16, n (%) 132 (41.0) 46 (28.6)a 17 (10.6)b 186 (37.6) 57 (23.1)b 24 (9.8)b

Week 24, n (%) 155 (48.1) 39 (24.2)b - 205 (41.4) 53 (21.5)b -

PSSD symptom score

Change from baseline N = 306 N = 158 N = 151 N = 466 N = 233 N = 239(mBOCF)**

Week 16, mean (SE) -26.7 (1.8) -17.8 (2.2)b -3.6 (2.1)b -28.3 (1.1) -21.1 (1.4)b -4.7 (1.4)b

Week 24, mean (SE) -31.9 (2.0) -20.7 (2.4)b - -29.1 (1.1) -21.4 (1.5)b -

PSSD sign score

Change from baseline N = 306 N = 158 N = 151 N = 466 N = 233 N = 239(mBOCF)*

Week 16, mean (SE) -28.9 (1.8) -20.0 (2.2)b -5.3 (2.1)a -31.9 (1) -23.8 (1.4)b -7.1 (1.4)b

Week 24, mean (SE) -33.8 (2.0) -22.5 (2.4)b - -32.4 (1.1) -24.2 (1.5)b -

* Patients with baseline score ≥ 2

** Adjusted mean change; mBOCF - modified baseline observation carried forward; standard error (SE)a p < 0.01 for comparison between deucravacitinib and placebo or deucravacitinib and apremilastb p < 0.0001 for comparison between deucravacitinib and placebo or deucravacitinib and apremilast

Of the 1519 patients with plaque psoriasis treated with deucravacitinib in clinical studies, 152 patientswere 65 years or older, including 21 patients who were 75 years or older (see section 4.2). No overalldifferences in exposure, safety or effectiveness were observed between older and younger patientswho received deucravacitinib.

Percent of Patients (%)

The European Medicines Agency has deferred the obligation to submit the results of studies with

SOTYKTU in one or more subsets of the paediatric population in the treatment of psoriasis (seesection 4.2 for information on paediatric use).

Deucravacitinib exhibited near complete oral absorption, dose-related increase in exposure, and noevident time-dependent pharmacokinetics.

Following oral administration of tablets, deucravacitinib exhibited rapid and near complete absorption.

The median Tmax ranged from 2 to 3 hours and absolute oral bioavailability was 99% in healthyvolunteers. Modest accumulation (<1.4-fold at steady state) was observed following once daily dosing.

Deucravacitinib can be administered without consideration for food or gastric pH modulators (H2receptor blockers and proton pump inhibitors). Co-administration of food or gastric pH modulators didnot affect total exposure (AUC[INF]) of deucravacitinib.

The volume of distribution at steady state (Vss), is 140 L, which is greater than total body water [42 L]indicating extravascular distribution. Deucravacitinib is 81.6% bound to human plasma proteins,primarily to human serum albumin.

Deucravacitinib distributes similarly between plasma and red blood cell components with blood-to-plasma concentration ratio of 1.26.

In humans, deucravacitinib is metabolised via four primary biotransformation pathways, whichinclude N-demethylation at the triazole moiety by cytochrome P-450 (CYP) 1A2 to form majormetabolite BMT-153261, cyclopropyl carboxamide hydrolysis by carboxylesterase 2 (CES2) to formmajor metabolite BMT-158170, N-glucuronidation by uridine glucuronyl transferase (UGT) to form

BMT-334616, and mono-oxidation by CYP 2B6/2D6 at the deuterated methyl group to form M11.

At steady state, deucravacitinib is the major circulating species constituting 49% of measuredcompound related components. Two major circulating metabolites, BMT-153261 and BMT-158170,were identified, both of which have half-lives comparable to the parent deucravacitinib. BMT-153261has comparable potency to the parent compound and BMT-158170 is not pharmacologically active.

The circulating exposure of BMT-153261 is much lower than the parent compound and therefore, thepredominant pharmacological activity is attributed to the parent compound deucravacitinib.

Additionally, no unique to human metabolites and no long-lived circulatory metabolites wereidentified.

Deucravacitinib is eliminated via multiple pathways, including Phase I and II metabolism, along withdirect renal and faecal elimination. Additionally, no single enzyme contributed more than 26% of totalclearance. Deucravacitinib is extensively metabolised, with 59% of orally administered[14C]-deucravacitinib dose eliminated as metabolites in urine (37% of the dose) and faeces (22% of thedose). Unchanged deucravacitinib in urine and faeces represented 13% and 26% of the dose,respectively.

The terminal elimination half-life of deucravacitinib 6 mg in healthy human adults is 10 hours, with atotal clearance of 15.3 L/h (CV 27%). Deucravacitinib is a substrate of efflux transporters,

P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) and uptake transporter OCT1. Dueto high passive permeability, high oral bioavailability and low affinity for these transporters,contribution of these transporters to deucravacitinib pharmacokinetics is minimal.

Deucravacitinib is not a substrate of transporters OATP, NTCP, OAT1, OAT3, OCT2, MATE1, or

MATE2K.

The pharmacokinetics of single doses of deucravacitinib administered as tablets was linear across 3 mgto 36 mg dose range.

Effect of deucravacitinib on other medicinal products

In vitro studies have shown no evidence that deucravacitinib and its major circulating metabolites, atclinically relevant exposures, inhibit major CYPs (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4), UGTs(1A1, 1A4, 1A6, 1A9, 2B7), CES2 and drug transporters (P-gp, BCRP, OATP1B1, OATP1B3, BSEP,

MRP2, OAT1, OAT3, OCT1, OCT2, MATE1, and MATE2K). Additionally, deucravacitinib does notinduce CYP 1A2, 2B6, and 3A4 (see section 4.5).

Based on the population pharmacokinetic analysis, deucravacitinib mean steady state exposure (Cavg,ss)was higher, 31% in patients aged 65-74 years [n = 87 of 1387 (6.3%)] and 53% in patients aged75-84 years [n = 13 of 1387 (0.94%)]. Exposures in patients aged ≥ 85 years old are not available.

Renal impairment has no clinically meaningful effect on deucravacitinib exposures (see section 4.2)based on a dedicated study where estimated glomerular filtration rate (eGFR) was determined using amodification of diet in renal disease (MDRD) equation. Compared to normal renal function group,deucravacitinib Cmax was altered by up to 15% and AUC[INF] increased by up to 48% across renalimpairment groups (mild (eGFR: ≥ 60 to < 90 mL/min), moderate (eGFR: ≥ 30 to < 60 mL/min),severe (eGFR: < 30 mL/min), and ESRD (eGFR: < 15 mL/min)). Compared to the normal renalfunction group, BMT-153261 Cmax increased by up to 34% and AUC[INF] increased up to 84% acrossrenal impairment groups.

Dialysis does not substantially clear deucravacitinib from systemic circulation (5.4% of dose clearedper dialysis).

Mild (Child-Pugh Class A) and moderate (Child-Pugh Class B) hepatic impairment has no clinicallymeaningful effect on deucravacitinib exposures (see section 4.2). Compared to normal hepaticfunction group, total deucravacitinib Cmax and AUC[INF] in mild and moderate hepatic impairmentgroup increased by up to 10% and 40%, respectively while the unbound deucravacitinib Cmax and

AUC(INF) increased by up to 26% and 60%, respectively. In severe (Child-Pugh Class C) hepaticimpaired adults, total deucravacitinib Cmax was comparable and total AUC was 43% higher relative tomatched healthy adults. In these adults, unbound Cmax and AUC(INF) increased by 62% and 131%,respectively. Deucravacitinib is not recommended for use in patients with severe hepatic impairment(see section 4.2).

The AUC(0-T) of BMT-153261 decreased by 19%, 53% and 76% in subjects with mild, moderate, andsevere hepatic impairment, respectively, compared to subjects with normal hepatic function, while

Cmax of BMT-153261, decreased by 25%, 59%, and 79% in subjects with mild, moderate, and severehepatic impairment, respectively.

Based on population pharmacokinetic modelling and simulation, females are expected to have anabout 30% higher deucravacitinib mean steady-state exposure (Cmax,ss and Cavg,ss) compared to male.

Based on population pharmacokinetic modelling and simulation, patients with lower body weight(< 60 kg) are expected to have a higher geometric mean steady-state exposure of deucravacitinib of37.4% (Cmaxss) and 24.8% (Cavgss). Patients with a higher body weight (> 90 kg) are expected to have alower geometric mean steady-state deucravacitinib exposure of 24.8% (Cmaxss) and 19.6% (Cavgss)(compared to patients with body weight 60-90 kg).

Intrinsic factors

Race, and ethnicity did not have a clinically meaningful effect on deucravacitinib exposure.

Non-clinical data reveal no special hazard for humans based on conventional studies of safetypharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity toreproduction and development.

In the chronic toxicity study in rats, decreases in lymphocyte counts, bone marrow cellularity andlymphoid cellularity in tissues of the immune system were observed at exposure (AUC) at lowest-observed-effect-level (LOEL) approximately 9 times the recommended human dose (RHD). Theseeffects were not associated with clinical signs of immunosuppression (e.g., infections). Decreases inplatelet counts and red blood cell (RBC) mass parameters were observed at exposure (AUC) at the

LOEL approximately 42 times the RHD. In the chronic toxicity study in monkeys, clinical andmicroscopic skin changes and decreased RBC mass parameters were observed at exposure (AUC) at

LOEL approximately 7 times the RHD.

Developmental and reproductive toxicity

Deucravacitinib had no effects on fertility or early embryonic development in male and female rats atexposures (AUC) up to approximately 247 and 171 times the RHD, respectively.

Deucravacitinib was neither embryo-lethal nor teratogenic at maternal exposures (AUC) up toapproximately 266 times the RHD in rats or 91/20 (total/free) times the RHD in rabbits.

In a pre- and post-natal development study in rats, transiently lower pup body weights were notedduring the pre-weaning period at maternal exposure (AUC) approximately 110 times the RHD. Thiseffect fully recovered during the post-weaning period.

Following administration of radiolabelled deucravacitinib to lactating rats, deucravacitinib and/or itsmetabolites were present in the milk with milk-to-plasma concentration ratios of 2.7 to 30.9.

Hypromellose acetate succinate

Anhydrous lactose

Microcrystalline cellulose

Croscarmellose sodium

Colloidal hydrated silica

Magnesium stearate

Polyvinyl alcohol

Titanium dioxide (E171)

Macrogol

Talc

Iron oxide red (E172)

Iron oxide yellow (E172)

Not applicable.

3 years.

This medicinal product does not require any special storage conditions.

Polyvinyl chloride/polychlorotrifluoroethylene (PVC/PCTFE) clear blister with push throughaluminium foil containing 7 or 14 film-coated tablets per blister (calendar or non-calendar blisters).

Pack sizes: 7, 14, 28 and 84 film-coated tablets.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

Bristol-Myers Squibb Pharma EEIG

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

EU/1/23/1718/001

EU/1/23/1718/002

EU/1/23/1718/003

EU/1/23/1718/004

EU/1/23/1718/005

EU/1/23/1718/006

EU/1/23/1718/007

EU/1/23/1718/008

Date of first authorisation:

Detailed information on this medicinal product is available on the website of the European Medicines

Agency http://www.ema.europa.eu.