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Week 16 Safety Profile1
ADVERSE REACTIONS THAT OCCURRED IN ≥1% OF PATIENTS TREATED WITH SOTYKTU AND MORE FREQUENTLY THAN PLACEBO THROUGH WEEK 16 FROM PSO-1 AND PSO-21
*Includes upper respiratory tract infection (viral, bacterial, and unspecified), nasopharyngitis, pharyngitis (including viral, streptococcal, and unspecified), sinusitis (includes acute, viral, bacterial), rhinitis, rhinotracheitis, tracheitis, laryngitis, and tonsillitis (including bacterial, streptococcal).1
†Includes oral herpes, genital herpes, herpes simplex, and herpes virus infection.1
‡Includes mouth ulceration, aphthous ulcer, tongue ulceration, and stomatitis.1
§Includes acne, acne cystic, and dermatitis acneiform.1
Week 16 Safety Profile (≥5%)2
AEs OCCURRING IN ≥5% OF PATIENTS IN ANY ACTIVE TREATMENT GROUP WEEKS 0-16 FROM POOLED CLINICAL TRIALS (PSO-1 AND PSO-2)2
*Includes 2 patients in SOTYKTU arm that were excluded from primary and secondary endpoint analyses.1
SAFETY PROFILE THROUGH
Adverse events for SOTYKTU, apremilast, and placebo2
PSO-1 AND PSO-2 POOLED SAFETY, WEEKS 0-522*
*Includes AEs between first dose and 30 days following last dose or rollover to long-term extension study.2
†Includes 2 patients in SOTYKTU arm that were excluded from primary and secondary endpoint analyses.1
AE=adverse event; AR=adverse reaction; EAIR=exposure-adjusted incidence rate; PY=patient years.
HCV=hepatitis C virus.
Established safety profile through 3 years*
OVERALL SAFETY SUMMARY
*Patients had varying lengths of treatment exposure.4
†Analysis includes 2 patients in the SOTYKTU arm who were excluded from primary and secondary endpoint analyses.
‡The LTE safety analysis represents the pooled POETYK PSO-1 and PSO-2 populations and patients enrolled in the LTE who were blindly switched from SOTYKTU, apremilast, or placebo to open-label SOTYKTU. All patients in the parent trials were eligible to enter the LTE after 52 weeks, regardless of initial treatment.3,4
§Data cutoff date of October 1, 2021. 79.0% of patients had total SOTYKTU exposure for ≥1 year and 39.9% for ≥2 years.3
||Data cutoff date of June 15, 2022. 77.6% of patients had total SOTYKTU exposure for >12 months and 22.4% for >36 months.4
AE=adverse event; EAR=exposure-adjusted incidence rate; LTE=long-term extension; PY=patient-years; QD=once daily; SAE=serious adverse event.
SOTYKTU, also known as deucravacitinib, is a novel, oral, selective, allosteric TYK2 inhibitor.
SOTYKTU is a tyrosine kinase 2 (TYK2) inhibitor indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
SOTYKTU is not recommended for use in combination with other potent immunosuppressants.
TYK2 mediates key pro-inflammatory cytokine signaling pathways of plaque psoriasis.
Psoriasis is a chronic immune mediated disorder. Around 2 million people in the US are estimated to have moderate-to-severe plaque psoriasis and approximately half of patients may have scalp involvement.
There are many pathways involved in psoriasis pathogenesis, including tyrosine kinase 2 (TYK2). TYK2 is a crucial intracellular enzyme that pairs with JAK1 or JAK2 to mediate various cytokine-signaling, such as interleukin-23 (IL-23).
IL-23 is a major pro-inflammatory cytokine involved in the survival and expansion of pathogenic T helper 17 cells, triggering the increased secretion of pro-inflammatory cytokines, including interleukin 17, which contributes to plaque psoriasis.
TYK2 is a central link in the IL-23/IL-17 axis in plaque psoriasis, making TYK2 a relevant kinase in the disease.
SOTYKTU binds to the regulatory domain of TYK2, which is unique across the TYK2 and JAK kinase family, stabilizing an inhibitory interaction between the regulatory and the catalytic domains, resulting in allosteric inhibition of receptor-mediated activation of TYK2 and its downstream activation of STATs.
The precise mechanism linking inhibition of TYK2 enzyme to therapeutic effectiveness in the treatment of adults with moderate-to-severe plaque psoriasis is not currently known.
In in-vitro assays, SOTYKTU has not been shown to inhibit JAK 1/2/3 pathways at clinically relevant doses.
SOTYKTU reduced psoriasis-associated gene expression in psoriatic skin in a dose dependent manner, including reductions in IL-23 pathway and Type I Interferon pathway-regulated genes.
Deucravacitinib reduced IL-17A, IL-19, and beta-defensin by 47 to 50%, 72%, and 81 to 84%, respectively, following 16 weeks of once daily treatment.
The relationship between these pharmacodynamic markers and the mechanism or mechanisms by which deucravacitinib exerts its clinical effects is unknown.
SOTYKTU is a first-in-class, oral allosteric TYK2 inhibitor, with a unique mechanism that binds a region specific to TYK2.]
Herpes virus reactivation (for example, herpes zoster, herpes simplex) was reported in clinical trials with SOTYKTU. Through Week 16, herpes simplex infections were reported in 17 patients (6.8 per 100 patient-years) treated with SOTYKTU, and 1 patient (0.8 per 100 patient-years) treated with placebo. Multi dermatomal herpes zoster was reported in an immunocompetent patient. During PSO-1, PSO-2, and the open-label extension trial, the majority of patients who reported events of herpes zoster while receiving SOTYKTU were under 50 years of age. The impact of SOTYKTU on chronic viral hepatitis reactivation is unknown. Consider viral hepatitis screening and monitoring for reactivation in accordance with clinical guidelines before starting and during therapy with SOTYKTU. If signs of reactivation occur, consult a hepatitis specialist. SOTYKTU is not recommended for use in patients with active hepatitis B or hepatitis C.
Tuberculosis (TB): In clinical trials, of 4 patients with latent TB who were treated with SOTYKTU and received appropriate TB prophylaxis, no patients developed active TB (during the mean follow-up of 34 weeks). One patient, who did not have latent TB, developed active TB after receiving 54 weeks of SOTYKTU. Evaluate patients for latent and active TB infection prior to initiating treatment with SOTYKTU. Do not administer SOTYKTU to patients with active TB. Initiate treatment of latent TB prior to administering SOTYKTU. Consider anti-TB therapy prior to initiation of SOTYKTU in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor patients for signs and symptoms of active TB during treatment.
Malignancy including Lymphomas: Malignancies, including lymphomas, were observed in clinical trials with SOTYKTU. 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) and patients who develop a malignancy when on treatment with SOTYKTU.
Rhabdomyolysis and Elevated CPK: Treatment with SOTYKTU was associated with an increased incidence of asymptomatic creatine phosphokinase (CPK) elevation and rhabdomyolysis compared to placebo. Discontinue SOTYKTU if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. Instruct patients to promptly report unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.
Laboratory Abnormalities: Treatment with SOTYKTU was associated with increases in triglyceride levels. Periodically evaluate serum triglycerides according to clinical guidelines during treatment. SOTYKTU treatment was associated with an increase in the incidence of liver enzyme elevation compared to placebo. Evaluate liver enzymes at baseline and thereafter in patients with known or suspected liver disease according to routine 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.
Immunizations: Prior to initiating therapy with SOTYKTU, consider completion of all age-appropriate immunizations according to current immunization guidelines including prophylactic herpes zoster vaccination. Avoid use of live vaccines in patients treated with SOTYKTU. The response to live or non-live vaccines has not been evaluated.
Potential Risks Related to JAK Inhibition: It is not known whether tyrosine kinase 2 (TYK2) inhibition may be associated with the observed or potential adverse reactions of Janus Kinase (JAK) inhibition. In a large, randomized, post marketing 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 is not approved for use in RA.
Most common adverse reactions (≥1% of patients on SOTYKTU and more frequently than with placebo) include upper respiratory infections, blood creatine phosphokinase increased, herpes simplex, mouth ulcers, folliculitis and acne.
Pregnancy: Available data from case reports on SOTYKTU use during pregnancy are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Report pregnancies to the Bristol-Myers Squibb Company’s Adverse Event reporting line at 1-800-721-5072.
Lactation: There are no data on the presence of SOTYKTU in human milk, the effects on the breastfed infant, or the effects on milk production. SOTYKTU is present in rat milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breast feeding should be considered along with the mother’s clinical need for SOTYKTU and any potential adverse effects on the breastfed infant from SOTYKTU or from the underlying maternal condition.
Hepatic Impairment: SOTYKTU is not recommended for use in patients with severe hepatic impairment.
SOTYKTU is available in 6 mg tablets.
Please see U.S. Full Prescribing Information, including Medication Guide, for SOTYKTU.