Consumer medicine information

Sotyktu

Deucravacitinib

BRAND INFORMATION

Brand name

Sotyktu

Active ingredient

Deucravacitinib

Schedule

SUMMARY CMI

SOTYKTU™

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

▼ This medicine is new or being used differently. Please report side effects. See the full CMI for further details.

1. Why am I using SOTYKTU?

SOTYKTU contains the active ingredient deucravacitinib.

SOTYKTU is used to treat adults with moderate to severe plaque psoriasis, an inflammatory condition affecting the skin, which can cause red, scaly, thick, itchy, painful patches on your skin and can also affect other areas of your body such as scalp, nails, hands, and feet. For more information, see Section 1. Why am I using SOTYKTU? in the full CMI.

2. What should I know before I use SOTYKTU?

Do not use if you have ever had an allergic reaction to deucravacitinib or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use SOTYKTU? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with SOTYKTU. See Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use SOTYKTU?

The recommended dose of SOTYKTU is one 6 mg tablet taken by mouth once a day.
Swallow the tablet whole. Do not crush, cut or chew the tablet.
It does not matter if you take this medicine before or after food.

More instructions can be found in Section 4. How do I use SOTYKTU? in the full CMI.

5. What should I know while using SOTYKTU?

Things you should do	Remind any doctor, dentist or pharmacist you visit that you are using SOTYKTU. Tell your doctor if you currently have an infection that does not go away or that keeps coming back
Things you should not do	Do not stop taking SOTYKTU without talking to your doctor first.
Driving or using machine	Be careful before you drive or use any machines or tools until you know how SOTYKTU affects you. This medicine is not likely to affect you being able to drive, cycle or use any tools or machines.
Looking after your medicine	Store below 30°C

For more information, see Section 5. What should I know while using SOTYKTU? in the full CMI.

6. Are there any side effects?

Common side effects include a cold, sore throat, runny or blocked nose, cough, sores in the mouth, cold sore blisters, acne-like rash and inflammation of hair follicles. Serious infections with fever, flu-like symptoms, tiredness, shortness of breath or cough which will not go away may need medical attention.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

▼ This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. You can report side effects to your doctor, or directly at www.tga.gov.au/reporting-problems.

FULL CMI

SOTYKTU™ (soh-tik-too)

Active ingredient: deucravacitinib (due-krav-a-sye-ti-nib)

Consumer Medicine Information (CMI)

This leaflet provides important information about using SOTYKTU. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using SOTYKTU.

Where to find information in this leaflet:

1. Why am I using SOTYKTU?
2. What should I know before I use SOTYKTU?
3. What if I am taking other medicines?
4. How do I take SOTYKTU?
5. What should I know while using SOTYKTU?
6. Are there any side effects?
7. Product details

1. Why am I using SOTYKTU?

SOTYKTU contains the active ingredient deucravacitinib.

It works by selectively blocking the activity of an enzyme called tyrosine kinase 2 (TYK2) which is involved in the process of inflammation. By reducing the activity of this enzyme, SOTYKTU can help to control the inflammation associated with psoriasis and reduce the signs and symptoms of this condition.

2. What should I know before I use SOTYKTU?

Warnings

Do not use SOTYKTU if:

you are allergic to deucravacitinib, or any of the ingredients listed at the end of this leaflet.
always check the ingredients to make sure you can use this medicine.

Check with your doctor if you:

currently have an infection that does not go away or that keeps coming back. SOTYKTU may lower the ability of your immune system to fight infections and may increase your risk of infections.
have or had hepatitis B or C
have or had tuberculosis. If you develop any of the symptoms of tuberculosis (a dry cough that doesn't go away, weight loss, fever, night sweats) call your doctor right away. Your doctor may test you for tuberculosis before starting SOTYKTU.
have cancer, because your doctor will have to decide if you can still be given SOTYKTU
recently had or plan to have a vaccination
have problems with your liver
have any other medical conditions
take any medicines for any other condition

Tell your doctor if you have unexplained muscle pain, tenderness or weakness, particularly if you have general body discomfort or fever.

Your doctor may take blood tests before you start treatment with SOTYKTU and while you are taking it. Depending on the results of your blood tests your doctor may suspend or discontinue treatment or prescribe you additional medicines.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. This is because it is not known how this medicine will affect the baby.

It is not known if SOTYKTU passes through breastmilk. Talk to your doctor if you are breastfeeding or intend to breastfeed.

Use in children or adolescents

This medicine is not recommended for use in children and adolescents under 18 years.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect SOTYKTU.

4. How do I take SOTYKTU?

How much to take

The recommended dose of SOTYKTU is one 6 mg tablet taken by mouth once a day.
Swallow the tablet whole. Do not crush, cut or chew the tablet.
It does not matter if you take this medicine before or after food.
Follow the instructions provided and use SOTYKTU until your doctor tells you to stop.

SOTYKTU comes in a calendar pack with the days of the week marked on it to help you remember to take your medicine each day. All of the tablets in the pack are the same.

If you forget to use SOTYKTU

SOTYKTU should be used regularly at the same time each day.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed.

If you use too much SOTYKTU

If you think that you have used too much SOTYKTU, you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using SOTYKTU?

Things you should do

Keep all of your doctor's appointments so that your progress can be checked.
Tell any other doctors, dentists, and pharmacists who are treating you that you are being treated with SOTYKTU.
Tell your doctor immediately if you become pregnant while being treated with SOTYKTU

Call your doctor straight away if you:

experience shortness of breath, wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body; rash; itching; or hives on the skin. These could be symptoms of serious allergic reaction.
currently have an infection that does not go away or that keeps coming back.
develop any of the symptoms of tuberculosis (a dry cough that doesn't go away, weight loss, fever, night sweats).

Remind any doctor, dentist or pharmacist you visit that you are using SOTYKTU.

Things you should not do

Do not stop taking SOTYKTU without talking to your doctor first.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how SOTYKTU affects you.

This medicine is not likely to affect you being able to drive, cycle or use any tools or machines.

Looking after your medicine

Store below 30°C

Follow the instructions on the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

in the bathroom or near a sink, or
in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Serious side effects

Serious side effects	What to do
Signs of a serious infection, such as fever, flu-like symptoms feeling tired or short of breath, cough which will not go away	Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Other side effects

Other Side effects

What to do

Very Common Side effects

upper respiratory tract infections with symptoms such as sore throat and stuffy nose

Common side effects

viral infection of the mouth
sores in the mouth
cold sore blisters
acne-like rashes
inflammation of hair follicles

Uncommon side effects

shingles (herpes zoster)

Speak to your doctor if you have any of these side effects and they worry you.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What SOTYKTU contains

Active ingredient (main ingredient)	deucravacitinib
Other ingredients (inactive ingredients)	hypromellose acetate succinate, lactose, microcrystalline cellulose, croscarmellose sodium, silicon dioxide, magnesium stearate Film coating: Opadry II Complete Film Coating System 85F140184 Pink (PI 141510)

Do not take this medicine if you are allergic to any of these ingredients.

What SOTYKTU looks like

SOTYKTU is pink, round, biconvex, film-coated tablet laser printed with "BMS 895 6 mg" on one side in two lines and no content on the other side (AUST R 376290).

Each pack contains 7 or 28 film-coated tablets.

Who distributes SOTYKTU

Bristol-Myers Squibb Australia Pty Ltd
4 Nexus Court, Mulgrave,
Victoria 3170, Australia.
Toll free number: 1800 067 567
Email: [email protected]

This leaflet was prepared in April 2024.

SOTYKTU is a trademark of Bristol-Myers Squibb Company.

Published by MIMS June 2024

BRAND INFORMATION

Brand name

Sotyktu

Active ingredient

Deucravacitinib

Schedule

1 Name of Medicine

Deucravacitinib.

2 Qualitative and Quantitative Composition

Each film-coated tablet contains 6 mg of deucravacitinib.

Excipient with known effect.

Lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Film-coated tablet.
Pink, round, biconvex, film-coated tablet laser printed with "BMS 895 6 mg" on one side in two lines and no content on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

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

4.2 Dose and Method of Administration

Dosage.

The recommended dose of Sotyktu is 6 mg once daily taken orally, with or without food. Do not crush, cut, or chew the tablet.

Dosage adjustment.

Renal impairment.

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

Hepatic impairment.

No dose adjustment is required in patients with mild or moderate hepatic impairment. Sotyktu is not recommended in patients with severe hepatic impairment (Child-Pugh Class C) (see Section 5.2 Pharmacokinetic Properties).

Paediatric population.

The safety and efficacy of Sotyktu in paediatric patients less than 18 years of age have not been established.

Elderly population.

No dose adjustment required in patients aged 65 years and older. There is limited information in patients aged ≥ 75 years old.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in Section 6.1 List of Excipients.

4.4 Special Warnings and Precautions for Use

Hypersensitivity.

Hypersensitivity reactions have been reported in clinical trials with Sotyktu, although causality is not established. If a clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue Sotyktu.

Infections.

Serious infections have been reported in clinical trials with Sotyktu (see Section 4.8 Adverse Effects (Undesirable Effects)).
Treatment with Sotyktu 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, deucravacitinib should be used with caution.
Patients treated with Sotyktu should be instructed to seek medical advice if signs or symptoms of clinically important infection occur. If a patient develops such an infection or is not responding to standard therapy, the patient should be monitored closely and Sotyktu discontinued until the infection resolves.

Viral reactivation.

Herpes virus reactivation (e.g. herpes zoster, herpes simplex) was reported in clinical trials with Sotyktu (see Section 4.8 Adverse Effects (Undesirable Effects)).
The impact of Sotyktu on chronic viral hepatitis reactivation is unknown. Patients with positive screening tests for hepatitis B or C, or chronic hepatitis B, or untreated hepatitis C were excluded from clinical trials. Consider viral hepatitis screening and monitoring for reactivation in accordance with clinical guidelines before starting therapy and during therapy with Sotyktu.

Pre-treatment evaluation for tuberculosis.

Prior to initiating treatment with Sotyktu, patients should be evaluated for tuberculosis (TB) infection. Do not administer Sotyktu to patients with active TB.
Anti-TB treatment should be considered prior to initiating Sotyktu in patients with active TB or a past history of latent TB in whom an adequate course of treatment cannot be confirmed. Patients receiving Sotyktu should be monitored for signs and symptoms of active TB.

Malignancies.

The risk of malignancies is increased in patients with psoriasis. Malignancies, including lymphomas, were observed in clinical trials with Sotyktu (see Section 4.8 Adverse Effects (Undesirable Effects)). Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Sotyktu, particularly in patients with a known malignancy (other than a successfully treated non-melanoma skin cancer [NMSC]) and patients who develop a malignancy when on treatment with Sotyktu.
NMSCs have been reported in patients treated with Sotyktu. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

Immunisations.

Prior to initiating therapy with Sotyktu, consider completion of all age-appropriate immunisations according to current immunisation guidelines. Avoid use of live vaccines in patients being treated with Sotyktu. The response to live or non-live vaccines has not been evaluated.

Potential risks of JAK inhibition.

It is not known whether TYK2 inhibition may be associated with the observed or potential adverse reactions of Janus Kinase (JAK) inhibition (see Section 5.1 Pharmacodynamic Properties). In a large, randomised, postmarketing safety trial of a JAK inhibitor in rheumatoid arthritis (RA), patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of all-cause mortality, including sudden cardiovascular death, major adverse cardiovascular events, overall thrombosis, deep venous thrombosis, pulmonary embolism, and malignancies (excluding non-melanoma skin cancer) were observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. Sotyktu has not been studied nor approved for use in RA.

Laboratory abnormalities.

Elevated CPK and rhabdomyolysis.

Discontinue Sotyktu if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever (see Section 4.8 Adverse Effects (Undesirable Effects)).

Triglyceride elevations.

Periodically evaluate serum triglycerides according to the clinical guidelines for hyperlipidemia while patients are receiving treatment with Sotyktu. Manage patients according to clinical guidelines for the management of hyperlipidemia (see Section 4.8 Adverse Effects (Undesirable Effects)).

Liver enzyme elevations.

Evaluate liver enzymes at baseline and thereafter in patients with known or suspected liver disease according to routine patient management. If treatment-related increases in liver enzymes occur and drug-induced liver injury is suspected, interrupt Sotyktu until a diagnosis of liver injury is excluded (see Section 4.8 Adverse Effects (Undesirable Effects)).

Use in elderly.

Of the 1519 patients with plaque psoriasis treated with Sotyktu, 152 patients were 65 years or older and 21 patients were 75 years or older (see Section 4.2 Dose and Method of Administration). No overall differences in deucravacitinib effectiveness were observed between patients 65 years of age and older and younger adult patients who received Sotyktu.
During the Week 0-16 period, for those subjects (80 subjects ≥ 65 years old, including 12 subjects ≥ 75 years old) who received Sotyktu without switching treatment arms, there was a higher rate of overall serious adverse events, including serious infections, and discontinuations due to adverse events compared with younger adults. Subjects in this age group who received placebo and apremilast also experienced a similar higher rate of overall serious adverse events.

Paediatric use.

The safety and efficacy of Sotyktu in paediatric patients less than 18 years of age have not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Effect of other medicinal products on deucravacitinib.

Deucravacitinib is eliminated via multiple pathways, including Phase I and II metabolism, direct renal and faecal elimination with no single pathway predominantly responsible for elimination. Therefore, major drug interactions via inhibition or induction of a pathway are not anticipated.
Deucravacitinib is a substrate of efflux transporters, P-glycoprotein and breast cancer resistance protein (BCRP) and uptake transporter OCT1. Due to 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, OAT2, OAT3, OCT2, MATE1, or MATE2K.
In dedicated drug interaction studies, no clinically meaningful changes in deucravacitinib were noted following coadministration of ciclosporin (dual Pgp/BCRP inhibitor), fluvoxamine (CYP1A2 inhibitor), ritonavir (CYP1A2 inducer), diflunisal (UGT 1A9 inhibitor), pyrimethamine (OCT1 inhibitor), and gastric pH modulating agents like famotidine (H₂ receptor antagonist) or rabeprazole (proton pump inhibitor).
No dose adjustment for deucravacitinib is required when coadministered with Pgp/BCRP inhibitors, strong CYP1A2 inhibitors, CYP1A2 inducers, UGT1A9 inhibitors, OCT1 inhibitors, or gastric pH modulators.

Effect of deucravacitinib on other medicinal products.

Based on in vitro data for deucravacitinib and its major circulating metabolites and clinical drug interaction studies, co-administration of deucravacitinib at 6 mg daily is not expected to have clinically relevant effects on exposures of agents that are substrates of CYPs (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4), UGTs (1A1, 1A4, 1A6, 1A9, 2B7), CES2 and drug transporters (Pgp, NTCP, OATP1B1, OATP1B3, BSEP, MRP2, OAT1, OAT3, OCT1, OCT2, MATE1, and MATE2K).
In dedicated drug interaction studies, deucravacitinib did not have a meaningful effect on exposures of concomitant medications rosuvastatin, methotrexate, mycophenolate mofetil (MMF) or oral contraceptives (norethindrone acetate and ethinyl estradiol).

Concomitant immunosuppressive therapy.

The safety and efficacy of deucravacitinib in combination with immunosuppressants, including biologics, have not been evaluated in patients with psoriasis.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The effect of deucravacitinib on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility.
In male rats, deucravacitinib had no effects on reproductive parameters (mating, fertility, and sperm morphology) or early embryonic development of their offspring at oral doses up to 50 mg/kg/day and exposure to total pharmacologically-active material approximately 248 times the maximum recommended human dose (MRHD).
In female rats, deucravacitinib had no effects on mating, fertility, or early embryonic parameters at oral doses up to 50 mg/kg/day and exposure approximately 144 times the MRHD.
(Category B1)
There are no adequate and well-controlled studies of deucravacitinib use in pregnant women. The data with deucravacitinib use in pregnant women are insufficient to inform on drug-associated risk. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.
Deucravacitinib was administered orally during the period of organogenesis at doses of up to 75 mg/kg/day in rats and up to 10 mg/kg/day in rabbits. Deucravacitinib was neither embryo-lethal nor teratogenic at the highest doses tested in either species. These doses resulted in maternal exposures (AUC) to total pharmacologically-active material that were approximately 223 times (rat) or 23 times (rabbit) the exposure at the MRHD.
In a pre- and post-natal development study in rats, deucravacitinib was administered from gestation day 6 through lactation day 20, at doses of 5, 15, or 50 mg/kg/day. At 50 mg/kg/day, pup body weight gain was lower, relative to control values, during the pre-weaning period; during post-weaning, their weights caught up and were comparable to those in control offspring after postnatal days 73 or 35 in males and females, respectively. There were no additional adverse findings in the F1 offspring, nor in F2 intrauterine survival. Maternal exposures to total pharmacologically-active material at 50 mg/kg/day were approximately 92 times the MRHD.
It is unknown whether deucravacitinib/metabolites are excreted in human milk.
A single oral dose of 5 mg/kg radiolabeled deucravacitinib was administered to lactating (post-partum days 8 to 12) rats. Deucravacitinib and/or its metabolites were present in the milk of lactating rats, with milk-to-plasma exposure ratio of 21. Deucravacitinib-related material was detected in breast-fed pups. Pup plasma levels of total pharmacologically-active material were 8-11% that in dams.

4.7 Effects on Ability to Drive and Use Machines

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

4.8 Adverse Effects (Undesirable Effects)

In clinical trials, a total of 1519 patients with moderate-to-severe plaque psoriasis received deucravacitinib 6 mg once daily. Of these, 1141 patients were exposed to deucravacitinib for at least one year.
Data from two placebo- and active-controlled trials (POETYK PSO-1 and POETYK PSO-2) were pooled to evaluate the safety of Sotyktu up to 16 weeks. In total, 842 patients were evaluated in the Sotyktu group.
During the 16-week placebo-controlled period, the incidence of serious adverse events was low and similar across treatment groups (Sotyktu 1.8%, placebo 2.9%, apremilast 1.2%) with no discernible trend in any specific type of serious adverse events.
Discontinuation of therapy due to adverse events during the 16-week placebo-controlled period was Sotyktu 2.4%, compared to placebo 3.8% and apremilast 5.2%.

Tabulated summary of adverse events.

Adverse events reported by ≥ 2% of subjects in any treatment group are provided in Table 1.

Description of selected adverse events.

The following adverse events have been reported in patients treated with Sotyktu. A causal relationship to Sotyktu is not established.
Tuberculosis. In clinical trials, of 4 subjects with latent TB who were treated with Sotyktu and received appropriate TB prophylaxis, no subjects developed active TB (during the mean follow-up of 34 weeks). One subject, who did not have latent TB, developed active TB after receiving 54 weeks of Sotyktu.
Laboratory abnormalities.

Elevated CPK and rhabdomyolysis.

Cases of rhabdomyolysis were reported in patients treated with Sotyktu resulting in interruption or discontinuation of Sotyktu dosing. In the 16-week placebo-controlled period, increased CPK (including Grade 4) was reported in 23 subjects (9.3 per 100 patient-years) treated with Sotyktu, and 5 subjects (4.1 per 100 patient-years) treated with placebo.

Triglyceride elevations.

Mean triglycerides concentrations increased by 10.3 mg/dL during the 16-week treatment period in subjects treated with Sotyktu and by 9.1 mg/dL during the 52-week treatment period. The effect of this elevated parameter on cardiovascular morbidity and mortality has not been determined.

Liver enzyme elevations.

There was an increased incidence of liver enzyme elevation with Sotyktu treatment compared to treatment with placebo. Liver serum transaminase elevations ≥ 3 times the ULN were reported in subjects treated with Sotyktu. In the 16-week placebo-controlled period:
ALT elevations ≥ 3 times the ULN was reported in 9 subjects (3.6 per 100 patient-years) treated with Sotyktu, and 2 subjects (1.6 per 100 patient-years) treated with placebo.
AST elevations ≥ 3 times the ULN was reported in 13 subjects (5.2 per 100 patient-years) treated with Sotyktu, and 2 subjects (1.6 per 100 patient-years) treated with placebo.

Tabulated list of adverse drug reactions (ADRs).

Adverse drug reactions that occurred in patients treated with Sotyktu during the 16-week controlled period are presented in Table 2. Through Week 52, no new ADRs were identified with Sotyktu and the incidence rates of common ADRs did not increase compared to those observed during the first 16 weeks of treatment.
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).

Description of selected adverse reactions.

Infections.

In POETYK PSO-1 and POETYK PSO-2 during the first 16 weeks, infections occurred in 29.1% of patients in the deucravacitinib group (116.0 events per 100 person-years) compared to 21.5% of patients in the placebo group (83.7 events per 100 person-years). The majority of infections were non-serious and mild to moderate in severity and did not lead to discontinuation of deucravacitinib. The incidence of serious infections in the deucravacitinib group was 0.6% (2.0 events per 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 per 100 person-years). The rate of serious infections in the deucravacitinib group did not increase through Week 52 (1.7 events per 100 person-years).
In the 16-week placebo-controlled period, herpes simplex infections were reported in 17 subjects (6.8 per 100 patient-years) treated with Sotyktu, and 1 subject (0.8 per 100 patient-years) treated with placebo. Multidermatomal herpes zoster was reported in a subject who received Sotyktu.
During PSO-1, PSO-2, and the open-label extension trial in which subjects who completed the controlled trials could enrol, the majority of subjects (10/18) who reported events of herpes zoster while receiving Sotyktu were under 50 years of age.

Malignancies.

During the 52-week treatment period of the two controlled psoriasis clinical studies (total exposure of 969.0 person-years with deucravacitinib), malignancies (excluding non-melanoma skin cancers) were reported in 0.2% of deucravacitinib-treated patients (0.3 events per 100 person-years), including one lymphoma. Lymphomas were also reported with deucravacitinib in the open-label, long-term extension and in an open-label regional study. The potential role of deucravacitinib in the development of malignancies is unclear.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Deucravacitinib has been administered in healthy subjects as single doses up to 40 mg (> 6 times the recommended human dose of 6 mg/day [RHD]) and in multiple doses up to 24 mg/day (12 mg twice daily) for 14 days without dose-limiting toxicity.
In case of overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment instituted immediately. Dialysis does not substantially clear deucravacitinib from systemic circulation (5.4% of dose cleared per dialysis treatment).
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Deucravacitinib is a small molecule that selectively inhibits the tyrosine kinase 2 (TYK2) enzyme. Deucravacitinib binds to the regulatory domain of TYK2, stabilising an inhibitory interaction between the 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 is a member of the Janus kinase (JAK) family. JAK kinases, including TYK2, function in pairs to mediate JAK-STAT pathways. TYK2 pairs with JAK1 to mediate multiple cytokine pathways and also pairs with JAK2 to transmit signals. The pairing of TYK2 with either JAK1 or JAK2 mediates signalling of a narrower range of cytokines compared with the pairings of JAKs 1/2/3 with each other. The allosteric mechanism of action of deucravacitinib has been shown to inhibit TYK2 with minimal or no inhibition of JAK 1/2/3. TYK2 mediates signalling of interleukin-23 (IL-23) cytokine, interleukin-12 (IL-12) cytokine, and type I interferons (IFN), which are naturally occurring cytokines involved in inflammatory and immune responses. Deucravacitinib inhibits signalling from IL-23, IL-12 and type I IFN and the downstream release of proinflammatory cytokines and chemokines.

Pharmacodynamic effects.

In healthy volunteers, the administration of deucravacitinib resulted in a dose- and concentration-dependent inhibition of two TYK2-dependent pathways indicating robust target engagement. These include IFN-alpha-induced STAT5 phosphorylation (mediated by TYK2/JAK1), and IL-12-induced IFN-gamma production (mediated by TYK2/JAK2) in ex vivo whole blood assays. The maximal inhibition was observed one hour after dosing which returned to near baseline by the end of dosing interval (12 or 24 hours). Further, IFN-regulated gene expression was inhibited in vivo in a dose dependent manner in subjects administered IFN-alpha, confirming that deucravacitinib inhibits TYK2 in vivo.
In a Phase 2 sub-study in subjects with psoriasis, deucravacitinib reduced psoriasis associated gene expression in psoriatic skin in a dose dependent manner, notably including reductions in IL-23-pathway and type I IFN pathway regulated genes. In Phase 2 and Phase 3 studies, deucravacitinib reduced levels of serum biomarkers associated with psoriasis disease activity. In Phase 3, IL-17A IL-19 and beta-defensin were reduced with deucravacitinib treatment by 47-50%, 72% and 81-84% respectively.

Cardiac electrophysiology.

At 7 times the maximum exposure achieved by the 6 mg once daily dose in psoriasis subjects, there was no clinically relevant effect on the QTc interval.

Clinical trials.

Plaque psoriasis. The efficacy and safety of Sotyktu 6 mg once daily were assessed in two multi-centre, randomised, double-blind, placebo- and active-controlled clinical studies, POETYK PSO-1 and POETYK PSO-2, which enrolled patients 18 years of age and older with moderate-to-severe plaque psoriasis who were eligible for systemic therapy or phototherapy. Patients had a body surface area (BSA) involvement of ≥ 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 to Sotyktu 6 mg once daily, 422 to apremilast 30 mg twice daily, and 421 to placebo.
In both studies, patients receiving placebo switched to Sotyktu at Week 16, which continued up to 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 Sotyktu and continued up to Week 52. In POETYK PSO-1 patients who were randomised to Sotyktu continued treatment up to Week 52. In POETYK PSO-2, Sotyktu-treated patients who achieved PASI 75 at Week 24 were re-randomised 1:1 to continue Sotyktu (maintenance) or were switched to placebo (withdrawal).
Both studies assessed the responses at Week 16 compared to placebo for the two co-primary endpoints:
the proportion of patients who achieved a sPGA score of 0 (clear) or 1 (almost clear);
the proportion of patients who achieved at least a 75% improvement in the PASI scores (PASI 75) from baseline.
Other comparisons between Sotyktu and placebo that were secondary endpoints at Week 16:
the proportion of patients who achieved PASI 90, PASI 100, sPGA 0, scalp-specific PGA (ss-PGA) score of 0 (clear) or 1 (almost clear), and Psoriasis Symptoms and Signs Diary (PSSD) Symptom Score of 0 (symptom-free).
Comparisons between Sotyktu and apremilast were made for the following secondary endpoints at these time points:
at Week 16 and 24 (POETYK PSO-1 and POETYK PSO-2), the proportion of patients who achieved PASI 75, PASI 90, and sPGA 0/1;
at Week 16 (POETYK PSO-1 and POETYK PSO-2), the proportion of patients who achieved sPGA 0 and ssPGA 0/1 (scalp).
Baseline disease characteristics were consistent for the study population in both studies with an overall median PASI score of 18.7, and a median BSA of 20%. Baseline sPGA score was 3 (moderate) in 79.8% of patients and 4 (severe) in 20.2%. Median Dermatology Life Quality Index (DLQI) score was 11. A total of 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 any systemic therapy (including biologic and/or non-biologic treatment), 41% received prior non-biologic systemic treatment, and 34.8% had received prior biologic therapy (16% TNF, 5% IL-12/23, 17% IL-17 and 4% IL-23 inhibitors).
Table 3 presents the efficacy results demonstrating superiority of Sotyktu compared to apremilast and placebo.

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

Response over time.

Sotyktu demonstrated rapid onset of efficacy, with higher percent improvement in PASI from baseline as compared with placebo as early as Week 1 (POETYK PSO-1 and PSO-2). The percentage of patients achieving a PASI 75 response was higher for Sotyktu compared to placebo by Week 4, with maximum PASI 75 response achieved by Week 24 (POETYK PSO-1 and PSO-2) and maintained through Week 52 (POETYK PSO-1) (see Figure 1).

In POETYK PSO-1, among patients initially randomised to apremilast who did not achieve PASI 50 response and were switched to Sotyktu at Week 24, 46.3% achieved PASI 75 response by Week 52.

Maintenance and durability of response.

In POETYK PSO-1, among patients who received Sotyktu and achieved PASI 75 response at Week 24, 81.3% of patients who continued on Sotyktu maintained PASI 75 response at Week 52. Among PASI 90 responders at Week 24, 73.6% of patients maintained PASI 90 response at Week 52. Among sPGA 0/1 responders at Week 24, 77.4% of patients maintained sPGA 0/1 response at Week 52.
In POETYK PSO-2, to evaluate maintenance and durability of response, patients who were originally randomised to Sotyktu and were PASI 75 responders at Week 24, were re-randomised to either continue treatment on Sotyktu or receive placebo. At Week 52, 80.4% of patients who continued on Sotyktu maintained PASI 75 compared to 31.3% of patients who were re-randomised to placebo withdrawn from Sotyktu. For responders at Week 24 who were re-randomised to placebo, the median time to loss of PASI 75 was approximately 12 weeks.
Figure 2 shows the PASI 75 responses in the two arms from Week 24-52.

Patient reported outcomes.

Significantly greater improvements in psoriasis symptoms (itch, pain, burning, stinging, and skin tightness) at Week 16 were observed with Sotyktu compared to apremilast in both studies based on the Psoriasis Symptoms and Signs Diary (PSSD) (Table 4). Significantly greater proportions of patients on Sotyktu compared to placebo achieved a PSSD symptom score of 0 (symptom-free) at Week 16 in both studies (Table 4).
Significantly greater proportions of patients on Sotyktu compared to placebo achieved a Dermatology Life Quality Index (DLQI) score of 0/1 (no effect at all on patient's life) at Week 16 in both studies (Table 4).
Improvement of these responses in patients receiving continuous Sotyktu treatment was observed through Week 24 and was maintained through Week 52 in POETYK PSO-1.

In addition, Sotyktu patients had significantly greater improvement from baseline compared to placebo in health-related quality of life at Week 16 as measured by the 36-item Short Form physical component summary (SF-36 PCS) and EQ-5D-3L Visual Analogue Scale (VAS). These improvements were maintained through Week 52.

5.2 Pharmacokinetic Properties

Deucravacitinib exhibited consistent oral absorption, dose-related increase in exposure, and no evident time-dependent pharmacokinetics. The pharmacokinetics of deucravacitinib administered as tablets was linear across a 3 mg to 36 mg dose range.

Absorption.

Following oral administration of tablets, deucravacitinib exhibited rapid and near complete absorption. The median T_max ranged from 2 to 3 hours and absolute oral bioavailability was 99%. Modest accumulation (< 1.4-fold) was observed following once daily dosing.
Deucravacitinib can be administered without consideration for food or gastric pH modulators (H₂ receptor blockers and proton pump inhibitors). Co-administration of food or gastric pH modulators did not affect total exposure (AUC_[INF]) of deucravacitinib.

Distribution.

The volume of distribution at steady state (Vss), at 140 L, is greater than total body water [42 L] indicating extravascular distribution. Deucravacitinib is 81.6% bound to human plasma proteins. Deucravacitinib distributes similarly between plasma and red blood cell components with blood-to-plasma concentration ratio of 1.26.

Metabolism.

In humans, deucravacitinib is mainly metabolised via three primary biotransformation pathways, which include N-demethylation at the triazole moiety by cytochrome P-450 (CYP) 1A2 to form major metabolite BMT-153261, cyclopropyl carboxamide hydrolysis by carboxylesterase 2 (CES2) to form major metabolite BMT-158170 and N-glucuronidation by uridine glucuronyl transferase (UGT) 1A9 to form BMT-334616.
At steady state, deucravacitinib is the major circulating species constituting 49% of measured drug-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-153261 has comparable potency to the parent drug and BMT-158170 has no clinically-relevant pharmacological activity. The circulating exposure of BMT-153261 accounts for approximately 20% of the systemic exposure of the total drug-related components.

Excretion.

Deucravacitinib is eliminated via multiple pathways including Phase I and II metabolism along with direct renal and faecal elimination. Additionally, no single enzyme or pathway contributed more than 26% of total clearance. Deucravacitinib was extensively metabolised, with 59% of the orally administered [¹⁴C]-deucravacitinib dose eliminated as metabolites in urine (37% of the dose) and faeces (22% of the dose). Unchanged deucravacitinib in urine and faeces represented 13% and 26% of the dose, respectively.
Terminal half-life in healthy human volunteers is 10 hours. Renal clearance of deucravacitinib ranges from 27 to 54 mL/min.

Special population.

Renal impairment.

Renal impairment has no clinically meaningful effect on deucravacitinib exposures (see Section 4.2 Dose and Method of Administration).
Compared to the normal renal function group, deucravacitinib C_max was 14% lower and 6% higher in patients with mild (eGFR ≥ 60 to < 90 mL/min/1.73 m²) and moderate (eGFR ≥ 30 to < 60 mL/min/1.73 m²) renal impairment, no change in C_max was observed in patients with severe (eGFR < 30 mL/min/1.73 m²) renal impairment, and ESRD (eGFR < 15 mL/min/1.73 m²) on dialysis. Deucravacitinib AUC_[INF] was unchanged in patients with mild renal impairment but higher by 39%, 28% and 34% in patients with moderate, severe and ESRD on dialysis, respectively, compared to subjects with normal renal function.
BMT-153261 C_max was 11% lower, 8% lower, 28% higher and 9% higher in patients with mild, moderate, severe renal impairment and ESRD on dialysis, respectively, compared to subjects with normal renal function. BMT-153261 AUC_[INF] was 2% lower, 24% higher, 81% higher and 27% higher in patients with mild, moderate, severe renal impairment and ESRD on dialysis, respectively, compared to subjects with normal renal function.
Dialysis did not substantially clear deucravacitinib from systemic circulation (5.4% of dose cleared per dialysis).

Hepatic impairment.

Mild (Child-Pugh Class A) and moderate (Child-Pugh Class B) hepatic impairment has no clinically meaningful effect on deucravacitinib exposures (see Section 4.2 Dose and Method of Administration).
Compared to normal hepatic function group, total deucravacitinib C_max was higher by 4%, 10% and 1% in patients with mild (Child-Pugh Class A), moderate (Child-Pugh Class B), and severe (Child-Pugh Class C) hepatic impairment, respectively. Deucravacitinib AUC_[INF] was higher by 10%, 40% and 43% in patients with mild, moderate, and severe hepatic impairment, respectively, compared to subjects with normal hepatic function.
BMT-153261 C_max was lower by 25%, 59% and 79% in patients with mild, moderate, and severe hepatic impairment, respectively, compared to subjects with normal hepatic function. BMT 153261 AUC_[INF] was lower by 3%, 20% and 50% in patients with mild, moderate, and severe hepatic impairment, respectively, compared to subjects with normal hepatic function.

Paediatric and adolescent.

The safety and efficacy of deucravacitinib in paediatric patients less than 18 years of age have not been established.

Intrinsic factors.

Body weight, gender, race, and ethnicity did not have a clinically meaningful effect on deucravacitinib exposure.

5.3 Preclinical Safety Data

Genotoxicity.

Deucravacitinib was not mutagenic in a bacterial mutagenicity assay (Ames test) or clastogenic in an in vitro chromosomal aberration assay (cultured Chinese hamster ovary cells) or in vivo in a rat peripheral blood micronucleus assay.

Carcinogenicity.

The carcinogenic potential of deucravacitinib was assessed in 6-month rasH2 transgenic mouse and 2-year rat studies. No evidence of tumorigenicity was observed in male or female Tg.rasH2 mice that received deucravacitinib at oral doses up to 60 mg/kg/day and exposure to total pharmacologically-active material 160 times the MRHD. No evidence of tumorigenicity was observed in male or female rats that received deucravacitinib at oral doses up to 15 mg/kg/day and exposure to total pharmacologically-active material approximately 43 times the MRHD.

6 Pharmaceutical Particulars

6.1 List of Excipients

Hypromellose acetate succinate, lactose, microcrystalline cellulose, croscarmellose sodium, silicon dioxide, magnesium stearate, film-coating: Opadry II Complete Film Coating System 85F140184 Pink (PI 141510).

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the ARTG. The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C. Store in original container.

6.5 Nature and Contents of Container

Polyvinyl chloride (PVC)/ polychlorotrifluoroethylene (PCTFE)/ aluminium foil blisters.
Pack sizes: 7 and 28 film-coated tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Molecular formula: C₂₀H₁₉²H₃N₈O₃.
Molecular weight: 425.47.
Chemical name: 6-(cyclopropanecarboxamido)-4-[2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)anilino]-N-(²H₃)methylpyridazine-3-carboxamide.

Chemical Abstract Service (CAS) registry number.

1609392-27-9.

Chemical structure.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

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