SOTYKTU has a unique MOA that selectively targets TYK2^1,2

NARRATOR: 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.

SOTYKTU is associated with the following warnings and precautions: Hypersensitivity, Infections, Tuberculosis, Malignancy including Lymphomas, Rhabdomyolysis and Elevated CPK, Laboratory Abnormalities, Immunizations, and Potential Risks Related to JAK Inhibition.

JEFFREY SOBELL: Hi. I'm Dr. Jeff Sobell and I'm excited to share my perspective on Sotyktu, a once-daily oral treatment option that I prescribe to a number of my adult patients with moderate-to-severe plaque psoriasis. Right now, I'm excited to discuss the mechanism of action and, importantly, the selectivity of Sotyktu.

So, Sotyktu is a first-in-class oral selective tyrosine kinase-2, or TYK2, inhibitor with a unique mechanism of action. As you can see on screen, TYK2 mediates multiple cytokine pathways, such as IL-23, which is a central cytokine in the pathogenesis of psoriasis.

So, as IL-23 binds to the IL-23 receptor on an inflammatory cell, such as a Th17 cell, a signal is transmitted to the nucleus to initiate the synthesis and release of IL-17, a cytokine which is key to the activation of keratinocytes in psoriasis. So, this secondary signal is sent to the nucleus, which provides an important link between IL-23 and IL-17, is mediated through the TYK2 molecule. So, TYK2 disrupts this intracellular pathway by inhibiting TYK2 signaling and, by doing so, inhibits the downstream activation of STATs, resulting in reduced IL-17 cytokine production.

On screen, please see pharmacodynamic information for SOTYKTU, from the U.S. Prescribing Information.

On the slide, you can see allosteric inhibition illustrated. Allosteric simply means that a drug binds to a location other than the active binding site. So, in this case, Sotyktu binds to the regulatory domain of TYK2 which, importantly, is structurally unique across the TYK2 and JAK kinase family and locks the molecule in its inactive state. In other words, it keeps it in a form that prevents ATP from binding, thus inhibiting pathway activation. As a result of this unique allosteric inhibition of TYK2, Sotyktu is selective for TYK2 and has not been shown to inhibit JAK1, 2, or 3 pathways at clinically relevant doses in in vitro assays.

Another way to demonstrate the selectivity of Sotyktu for TYK2 is to observe on screen the simulated daily average inhibition of Sotyktu 6 mg a day in whole blood-based assays, which here shows 50% daily inhibition of TYK2 and less than 1% inhibition of JAKs 1, 2, and 3. Now keep in mind that I have described the proposed scientific pathway, but 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.

So, the take-home message for this chapter is that Sotyktu represents a first in a new class of medicines with its unique mechanism of action of allosteric inhibition of TYK2. As I said, I’ve prescribed Sotyktu for a lot of my adult patients with moderate-to-severe plaque psoriasis and will continue to consider it as a treatment option for appropriate patients.

NARRATOR:

IMPORTANT SAFETY INFORMATION

INDICATION

SOTYKTU (deucravacitinib) is indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

Limitations of Use:

SOTYKTU is not recommended for use in combination with other potent immunosuppressants.

CONTRAINDICATIONS

SOTYKTU is contraindicated in patients with a history of hypersensitivity reaction to deucravacitinib or to any of the excipients in SOTYKTU.

WARNINGS AND PRECAUTIONS

Hypersensitivity: Hypersensitivity reactions such as angioedema have been reported. If a clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue SOTYKTU.

Infections: SOTYKTU may increase the risk of infections. Serious infections have been reported in patients with psoriasis who received SOTYKTU. The most common serious infections reported with SOTYKTU included pneumonia and COVID-19. Avoid use of SOTYKTU in patients with an active or serious infection. Consider the risks and benefits of treatment prior to initiating SOTYKTU in patients:

• with chronic or recurrent infection
• who have been exposed to tuberculosis
• with a history of a serious or an opportunistic infection
• with underlying conditions that may predispose them to infection.

Closely monitor patients for the development of signs and symptoms of infection during and after treatment. A patient who develops a new infection during treatment should undergo prompt and complete diagnostic testing, have appropriate antimicrobial therapy initiated and be closely monitored. Interrupt SOTYKTU if a patient develops a serious infection. Do not resume SOTYKTU until the infection resolves or is adequately treated.

Viral Reactivation

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.

ADVERSE REACTIONS

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.

SPECIFIC POPULATIONS

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.