SOTYKTU™ (deucravacitinib) Efficacy

Co-primary

Superior PASI 75 and sPGA 0/1 response rates vs placebo^1,3,4

In POETYK PSO-1 and POETYK
PSO-2, superior PASI 75 response rates vs placebo at Week 16

sPGA response of 0/1 at Week 16 vs placebo (co-primary endpoint)^1-3

In POETYK PSO-1, 54% for SOTYKTU vs 7% for placebo, P<0.0001
In POETYK PSO-2, 50% for SOTYKTU vs 9% for placebo, P<0.0001

Study design¹

POETYK PSO-1 (N=664) and POETYK PSO-2 (N=1020) were two, 52-week, multicenter, randomized, double-blind, placebo- and active (apremilast 30 mg twice daily)-controlled, Phase 3 studies to evaluate the safety and efficacy of SOTYKTU (6 mg once daily) in adult patients 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 Physicians Global Assessment (sPGA) ≥3 (moderate or severe).

Both studies assessed the responses at Week 16 compared with placebo for the two co-primary endpoints:

The proportion of patients who achieved at least a 75% improvement in PASI scores from baseline (PASI 75)
The proportion of patients who achieved an sPGA score of 0 (clear) or 1 (almost clear)

There were multiple ranked secondary endpoints, including:

The proportion of patients who achieved PASI 75 at Week 16 and Week 24 vs apremilast
The proportion of patients who achieved at least a 90% improvement in PASI scores from baseline
(PASI 90) at Week 16 and Week 24 vs apremilast
The proportion of patients who achieved a scalp-specific PGA (ss-PGA) score of 0 (clear) or 1 (almost clear) at Week 16 vs placebo and vs apremilast

PASI 75

Demonstrated superior response rates vs apremilast^1,4,5

In POETYK PSO-1, superior PASI 75 response rate vs apremilast at Weeks 16 and 24 (secondary endpoints)^1,4

POETYK PSO-1 PASI 75 Response Rates (NRI)1,4

POETYK PSO-1 PASI 75 Response Rates (NRI)1,3,4

sPGA 0/1 response rates at Week 24 (secondary endpoints)¹

In POETYK PSO-1, sPGA 0/1 response rates at Week 24 were 59% for SOTYKTU (n=330) vs 31% for apremilast (n=168); P<0.0001
In POETYK PSO-2, sPGA 0/1 response rates at Week 24 were 49% for SOTYKTU (n=511) vs 30% for apremilast (n=254); P<0.0001

sPGA=static Physician’s Global Assessment. sPGA response defined as PGA score of 0 or 1 with ≥2-point improvement from baseline.

PASI 75 Response Rate at Week 52 (additional endpoint)⁴

In POETYK PSO-1, 65% of patients receiving continuous SOTYKTU (n=330) achieved PASI 75 at Week 52

PASI 75 at Week 52 was not a ranked primary or secondary endpoint and was analyzed descriptively. In POETYK PSO-2, the same analysis at Week 52 is not available due to the trial design and forced re-randomization.

SELECT IMPORTANT SAFETY INFORMATION:

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

Please See Additional Important Safety Information Below

Maintenance of response¹ (additional endpoint)

PASI 75 and sPGA 0/1 responders at Week 24 who maintained response at Week 52 in PSO-1

82 % of patients who achieved PASI 75 at week 24 maintained it through 1 Year

78% (n=151/194) of patients who achieved sPGA 0/1 at Week 24 maintained it at 1 year

Maintenance of response in POETYK PSO-2 (additional endpoints)

To evaluate maintenance and durability of response, patients in PSO-2 who were originally randomized to SOTYKTU and were PASI 75 responders at Week 24 were re-randomized to either continue treatment on SOTYKTU or be withdrawn from therapy (ie, receive placebo)
At 1 year, 80% (n=119/148) of patients who continued on SOTYKTU maintained PASI 75 compared to 31% (n=47/150) of patients who were withdrawn from treatment with SOTYKTU
70% (n=83/118) of SOTYKTU patients who were re-randomized and who also achieved sPGA 0/1 at Week 24 maintained it at 1 year compared to 24% (n=28/119) of patients who were withdrawn from treatment with SOTYKTU

Study design¹

POETYK PSO-1 (N=664) and POETYK PSO-2 (N=1020) were two, 52-week, multicenter, randomized, double-blind, placebo- and active (apremilast 30 mg twice daily)-controlled, Phase 3 studies to evaluate the safety and efficacy of SOTYKTU (6 mg once daily) in adult patients 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 Physicians Global Assessment (sPGA) ≥3 (moderate or severe).

Both studies assessed the responses at Week 16 compared with placebo for the two co-primary endpoints:

The proportion of patients who achieved at least a 75% improvement in PASI scores from baseline (PASI 75)
The proportion of patients who achieved an sPGA score of 0 (clear) or 1 (almost clear)

There were multiple ranked secondary endpoints, including:

The proportion of patients who achieved PASI 75 at Week 16 and Week 24 vs apremilast
The proportion of patients who achieved at least a 90% improvement in PASI scores from baseline
(PASI 90) at Week 16 and Week 24 vs apremilast
The proportion of patients who achieved a scalp-specific PGA (ss-PGA) score of 0 (clear) or 1 (almost clear) at Week 16 vs placebo and vs apremilast

STUDY RESULTS^1,4,5

Co-primary endpoints:

PASI 75 at Week 16 for SOTYKTU vs placebo: PSO-1: 58% (n=193/330) vs 13% (n=21/166), P<0.0001; PSO-2: 53% (n=271/511) vs 9% (n=24/255), P<0.0001
sPGA 0/1 at Week 16 for SOTYKTU vs placebo: PSO-1: 54% (n=178/330) vs 7% (n=12/166), P<0.0001; PSO-2: 50% (n=253/511) vs 9% (n=22/255), P<0.0001

Select secondary endpoint:

PASI 75 at Week 16 for SOTYKTU vs apremilast: PSO-1: 58% (n=193/330) vs 35% (n=59/168), P<0.0001; PSO-2: 53% (n=271/511) vs 40% (n=101/254), P=0.0004

SELECT IMPORTANT SAFETY INFORMATION:

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

PEER PERSPECTIVES: CLEARER CHOICE

Learn more about SOTYKTU and why a leader in the dermatology field considers it to be a clearer choice vs Otezla® (apremilast) for adult patients with moderate-to-severe plaque psoriasis

View transcript +

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

NEAL BHATIA: Hi. I'm Dr. Neal Bhatia 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'd like to focus on clinical settings where I consider Sotyktu. I often choose Sotyktu for my patients when looking for a first-line oral systemic option due to its superior skin clearance versus apremilast in the pivotal trials, safety and efficacy data through two years in clinical trials, and once-daily dosing. The once-daily aspect really appeals to some of my patients.

In Phase 3 clinical trials, POETYK PSO-1 and POETYK PSO-2, Sotyktu not only met co-primary endpoints versus placebo, but also achieved superior skin clearance versus apremilast in several secondary endpoints. As you can see, at week 24 in POETYK PSO-1, Sotyktu achieved a 69% PASI 75 response rate compared with 38% for apremilast. In PSO-2, the rates were 58% versus 38% respectively.

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.

Sotyktu really demonstrated its efficacy potential with its PASI 90 data where it once again showed superiority to apremilast. In week 24 in POETYK PSO-1, Sotyktu achieved a 42% PASI 90 response rate compared with 22% for apremilast. In PSO-2, the rates were 32% versus 20%, respectively.

Of note, Sotyktu also showed efficacy in a hard-to-treat area, the scalp. At week 16 in POETYK PSO-1, Sotyktu achieved a 70% ss-PGA of clear or almost clear response compared with 39% for apremilast. In PSO-2, the rates were 60% versus 37%, respectively.

Coupled with this efficacy data, I also consider Sotyktu’s safety and tolerability profile. Seen here are the rates of most common adverse reactions reported through week 16 in at least 1% of patients on Sotyktu and more frequently than placebo, which included upper respiratory infections, blood creatinine phosphokinase increase, herpes simplex, mouth ulcers, folliculitis, and acne.

Another measure I look at is the discontinuation rate within the clinical trial. As you can see on screen, at week 16 the discontinuation rate was 2.4% for Sotyktu, 3.8% for placebo, and 5.2% for apremilast.

Please note, these studies were not designed to compare the safety of apremilast to Sotyktu. Some of the observed safety rates for apremilast may differ from those previously reported. Please refer to the apremilast full prescribing information.

As I said, I prescribe 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.

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

Adverse Reactions graphic that occurred in less than 1% of patients

AE=adverse event; AR=adverse reaction; CPK=creatine phosphokinase.

*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).

^†Includes oral herpes, genital herpes, herpes simplex, and herpes virus infection.

^‡Includes mouth ulceration, aphthous ulcer, tongue ulceration, and stomatitis.

^§Includes acne, acne cystic, and dermatitis acneiform.

Adverse reactions that occurred in <1% of patients in the SOTYKTU group were herpes zoster¹

Infections¹

In the first 16 weeks, infections occurred in 29% of the SOTYKTU group (116/100 PY) compared to 22% of the placebo group (83.7/100 PY). The majority of infections were non-serious and mild to moderate in severity and did not lead to discontinuation of SOTYKTU. The incidence of serious infections were reported in 5 patients (2.0/100 PY) treated with SOTYKTU, and 2 patients (1.6/100 PY) treated with placebo. The most common serious infections reported during the 52-week treatment period were pneumonia and COVID-19.

Malignancies¹

Malignancies (excluding non-melanoma skin cancer) through Week 52 (total exposure of 986 PY with SOTYKTU) were reported in 3 patients treated with SOTYKTU (0.3/100 PY). During POETYK PSO-1, POETYK PSO-2, and the open-label extension trial, 3 patients (0.1/100 PY) developed lymphoma while receiving SOTYKTU.

Safety through Week 52¹

In PSO-1 and PSO-2, the exposure-adjusted incidence rate of adverse reactions in patients treated with SOTYKTU from Week 0 through Week 52 without switching treatment did not increase compared to the rate observed during the first 16 weeks of treatment.

PY=patient years

PASI 90

Superior PASI 90 response rates vs apremilast^1,4,5

In POETYK PSO-1, nearly twice the PASI 90 response rate with SOTYKTU vs apremilast at Week 24 (secondary endpoint)^1,4

POETYK PSO-1 PASI 90 Response Rates (NRI)1,4

Superior PASI 90 response rates vs apremilast at Week 16 and Week 24 (secondary endpoints) were also seen in POETYK PSO-2^1,5

PASI 90 at Week 16 and Week 24 were secondary endpoints

PASI 90 Response Rate at Week 52 (additional endpoint)⁴

In POETYK PSO-1, 44% of patients receiving continuous SOTYKTU (n=330) achieved PASI 90 at Week 52

PASI 90 at Week 52 was not a ranked primary or secondary endpoint and was analyzed descriptively. In POETYK PSO-2, the same analysis at Week 52 is not available due to the trial design and forced re-randomization.

SELECT IMPORTANT SAFETY INFORMATION:

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 (e.g., 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. Multidermatomal 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

Maintenance of response for SOTYKTU in POETYK PSO-1 (additional endpoint)

PASI 90 responders at Week 24 who maintained response at Week 52¹

74% of patients who achieved PASI 90 at week 24 maintained it through Year 1

Study design¹

POETYK PSO-1 (N=664) and POETYK PSO-2 (N=1020) were two, 52-week, multicenter, randomized, double-blind, placebo- and active (apremilast 30 mg twice daily)-controlled, Phase 3 studies to evaluate the safety and efficacy of SOTYKTU (6 mg once daily) in adult patients 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 Physicians Global Assessment (sPGA) ≥3 (moderate or severe).

Both studies assessed the responses at Week 16 compared with placebo for the two co-primary endpoints:

The proportion of patients who achieved at least a 75% improvement in PASI scores from baseline (PASI 75)
The proportion of patients who achieved an sPGA score of 0 (clear) or 1 (almost clear)

There were multiple ranked secondary endpoints, including:

The proportion of patients who achieved PASI 75 at Week 16 and Week 24 vs apremilast
The proportion of patients who achieved at least a 90% improvement in PASI scores from baseline
(PASI 90) at Week 16 and Week 24 vs apremilast
The proportion of patients who achieved a scalp-specific PGA (ss-PGA) score of 0 (clear) or 1 (almost clear) at Week 16 vs placebo and vs apremilast

STUDY RESULTS^1-3

Co-primary endpoints:

PASI 75 at Week 16 for SOTYKTU vs placebo: PSO-1: 58% (n=193/330) vs 13% (n=21/166), P<0.0001; PSO-2: 53% (n=271/511) vs 9% (n=24/255), P<0.0001
sPGA 0/1 at Week 16 for SOTYKTU vs placebo: PSO-1: 54% (n=178/330) vs 7% (n=12/166), P<0.0001; PSO-2: 50% (n=253/511) vs 9% (n=22/255), P<0.0001

Select secondary endpoint:

PASI 90 at Week 24 for SOTYKTU vs apremilast: PSO-1: 42% (n=140/330) vs 22% (n=37/168), P<0.0001; PSO-2: 32% (n=164/511) vs 20% (n=50/254), P=0.0002

SELECT IMPORTANT SAFETY INFORMATION:

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.