INDICATIONS

WEZLANA is indicated for the treatment of:

  • patients 6 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.
  • patients 6 years or older with active psoriatic arthritis...Read more
  • adult patients with moderately to severely active Crohn’s disease.
  • adult patients with moderately to severely active ulcerative colitis.
  • patients 6 years or older with moderate to severe plaque psoriasis who are candidates...Read more for phototherapy or systemic therapy.
  • patients 6 years or older with active psoriatic arthritis.
  • adult patients with moderately to severely active Crohn’s disease.
  • adult patients with moderately to severely active ulcerative colitis.

WEZLANA is an ustekinumab biosimilar approved for all STELARA indications based on the totality of evidence1-6

WEZLANA is FDA approved for:1

Moderate to severe

  • Plaque psoriasis in adults and pediatric patients aged ≥ 6 years who are candidates for phototherapy or systemic therapy

Moderately to severely ACTIVE

  • Crohn’s disease in adults
  • Ulcerative colitis in adults

ACTIVE

  • Psoriatic arthritis in adults and pediatric patients aged ≥ 6 years
  • Study design
    A rigorous clinical study compared WEZLANA to STELARA7
    Trial design for comparative study of WEZLANA™ (ustekinumab-auub) vs ustekinumab involving patients with moderate to severe plaque psoriasis
    Trial design for comparative study of WEZLANA™ (ustekinumab-auub) vs ustekinumab involving patients with moderate to severe plaque psoriasis

    Study population: Adult patients (aged ≥ 18 and ≤ 75 years) with stable moderate to severe plaque psoriasis for ≥ 6 months with previous failure, inadequate response, intolerance, or contraindication to ≥ 1 conventional anti-psoriatic systemic therapy.

    Primary endpoint: Percentage change in PASI from baseline to week 12.

    Secondary endpoint: PASI percent improvement at other time points.

    Dosing: 45 mg (if baseline BW ≤ 100 kg) or 90 mg (if baseline BW > 100 kg).

    BW = body weight; PASI = psoriasis area severity index; PASI 50/75 = ≥ 50% / ≥ 75% improvement from baseline in PASI score; PsO = psoriasis; Q12W = every 12 weeks;

    R = randomization; SC = subcutaneous.

    BW = body weight; PASI = psoriasis area severity index; PASI 50/75 = ≥ 50% / ≥ 75% improvement from baseline in PASI score; PsO = psoriasis; Q12W = every 12 weeks; R = randomization; SC = subcutaneous.

  • PASI Improvements
    PASI improvements with WEZLANA8
    Graph illustrating percent improvement in PASI from baseline for WEZLANA™ (ustekinumab-auub) and Stelara through 52 weeks.
    Graph illustrating percent improvement in PASI from baseline for WEZLANA™ (ustekinumab-auub) and Stelara through 52 weeks.

    Highly similar efficacy was demonstrated with no clinically meaningful differences vs STELARA

    PASI percentage improvement from baseline to week 12 (primary endpoint) was similar for both groups:

    Bar charts comparing PASI percentage improvement of WEZLANA™ (ustekinumab-auub) and Stelara, from baseline to week 12. Bar charts comparing PASI percentage improvement of WEZLANA™ (ustekinumab-auub) and Stelara, from baseline to week 12.

    PASI = Psoriasis Area Severity Index; PsO = psoriasis.

  • Safety/immunogenicity
    Similar safety profile was demonstrated in patients who transitioned to WEZLANA from STELARA8

    Adverse Events Experienced by ≥ 2% of Subjects in Any Treatment Group by Preferred Term—Entire Study

    WEZLANA/WEZLANA n = 247 STELARA/WEZLANA n = 117 STELARA/STELARA n = 116
    Preferred term % n % n % n
    COVID-19 11.7 29 13.7 16 10.3 12
    Nasopharyngitis 5.7 14 0.9 1 8.6 10
    Upper respiratory tract infection 4.5 11 6.0 7 5.2 6
    Hypertension 3.2 8 1.7 2 4.3 5
    Headache 2.4 6 4.3 5 1.7 2

    Anti-drug Antibody (ADA) Result—Entire Study

    WEZLANA/WEZLANA n = 247 STELARA/WEZLANA n = 117 STELARA/STELARA n = 116
    Result % n % n % n
    Neutralizing ADA positive anytime 9.7 24 17.9 21 15.5 18

    PsO = psoriasis.

  • Study design
    Safety and efficacy evaluated in a switching study of patients with moderate to severe plaque psoriasis9
    Trial design for switching study involving WEZLANA™ (ustekinumab-auub) and ustekinumab involving patients with moderate to severe plaque psoriasis.
    Trial design for switching study involving WEZLANA™ (ustekinumab-auub) and ustekinumab involving patients with moderate to severe plaque psoriasis.

    Study population: Adult patients (aged ≥ 18 and ≤ 75 years) with stable moderate to severe plaque psoriasis for ≥ 6 months, with previous failure, inadequate response, intolerance, or contraindication to ≥ 1 conventional anti-psoriatic systemic therapy.

    Primary endpoint: AUCtau and Cmax from week 52 (pre-dose and post-dose) until week 64.

    Dosing: 45 mg (if baseline BW ≤ 100 kg) or 90 mg (if baseline BW > 100 kg).

    BW = body weight; PASI = Psoriasis Area Severity Index; PASI 50 = ≥ 50% improvement from baseline in PASI score; PK = pharmacokinetic; PsO = psoriasis; R = randomization; SC = subcutaneous.

    BW = body weight; PASI = Psoriasis Area Severity Index; PASI 50 = ≥ 50% improvement from baseline in PASI score; PK = pharmacokinetic; PsO = psoriasis; R = randomization; SC = subcutaneous.

    *Patients achieving PASI 50 response or better were randomized at week 28 (1:1) to continue STELARA or switch between WEZLANA and STELARA every 12 weeks up to week 52.

    †At week 28, run-in failures were not randomized and completed end of study procedures at week 28.

  • PASI RESULTS
    Multiple switches had no meaningful impact on PK parameters or PASI results10

    Mean Serum Concentration-Time Profiles Between Week 52 and Week 64 (Primary Endpoint)

    Graph illustrating mean serum concentration-time profiles from a study involving patients treated with either WEZLANA™ (ustekinumab-auub) or both WEZLANA™ and Stelara (switching group) between week 52 and week 64.
    Graph illustrating mean serum concentration-time profiles from a study involving patients treated with either WEZLANA™ (ustekinumab-auub) or both WEZLANA™ and Stelara (switching group) between week 52 and week 64.

    PASI percentage improvement from baseline to week 64 was similar for both groups

    Bar charts comparing PASI percentage improvement from a study involving patients treated with WEZLANA™ (ustekinumab-auub) or both WEZLANA™ and Stelara (switching group), from baseline to week 64

    PsO = psoriasis.

  • Safety/immunogenicity
    Similar safety profile was demonstrated in patients who experienced multiple switches10

    Adverse Events Experienced by ≥ 2% of Subjects in Any Treatment Group by Preferred Term—Safety Analysis Set

    Switching Group n = 217 Continued Use Group n = 216
    Preferred term % n % n
    COVID-19 12.4 27 11.6 25
    Upper respiratory tract infection 6.5 14 6.5 14
    Nasopharyngitis 5.5 12 7.4 16
    Headache 2.3 5 0.5 1
    Hypertension 2.3 5 1.9 4

    Anti-drug Antibody Result—Entire Study

    Switching Group n = 217 Continued Use Group n = 216
    Result % n % n
    Neutralizing antibody positive with negative/no result* 3.7 8 2.8 6

    PsO = psoriasis.

    *Prior to first dose post-randomization.

  • Extrapolation
    Data in sensitive patient populations help support a biosimilar’s approval in other indications.11 Extrapolation of data is an established scientific and regulatory principle11
    Diagram illustrating the established scientific and regulatory principle of data extrapolation.
    Diagram illustrating the established scientific and regulatory principle of data extrapolation

    MOA = mechanism of action.

  • Sensitive population
    WEZLANA was studied in a sensitive population (moderate to severe plaque PsO) and endpoint7,11

    Sensitive patient population11

    • Helps detect clinically meaningful differences between a biosimilar and reference drug

    Sensitive primary endpoint11,13

    • Reduces patient- and disease-related confounding factors in biosimilar studies

    PsO = psoriasis.

  • Approval process
    WEZLANA was evaluated through an extensive development program
    Molecular similarity | Clinical Pharmacology Studies | Comparative clinical data
    Molecular similarity | Nonclinical Studies | Clinical Pharmacology Studies | Comparative clinical data

    In addition to studies conducted as part of FDA biosimilar and interchangeable determination, Amgen conducted a switching study showing consistent safety/efficacy when switching between STELARA and WEZLANA.9,10

    A rigorous stepwise approach determined the biosimilarity and interchangeability of WEZLANA to STELARA

    ADA = anti-drug antibodies; FDA = US Food and Drug Administration; PD = pharmacodynamic; PK = pharmacokinetic.

  • Pharmacokinetics
    Overlapping data curves demonstrate WEZLANA bioequivalence to STELARA5
    Overlapping data curves illustrating WEZLANA™ (ustekinumab-auub) bioequivalence to Stelara.
    Overlapping data curves illustrating WEZLANA™ (ustekinumab-auub) bioequivalence to Stelara.

    Study design: A randomized, double-blind, single-dose, 3-arm parallel group study in healthy adults (N = 238) who received 90 mg of WEZLANA, STELARA US, or STELARA EU.5

    Primary endpoint: Pharmacokinetics assessed by the area under the serum concentration-time curve from time 0 to infinity and the Cmax.5

    Serum concentrations of WEZLANA and STELARA were highly similar at all timepoints measured5

    PsO = psoriasis.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

WEZLANA is contraindicated in patients with clinically significant hypersensitivity to ustekinumab products or to any of the excipients.

INFECTIONS

Ustekinumab products may increase the risk of infections and reactivation of latent infections. Serious bacterial, mycobacterial, fungal, and viral infections requiring hospitalization or otherwise clinically significant infections were reported. In patients with plaque psoriasis, these included diverticulitis, cellulitis, pneumonia, appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, gastroenteritis, and urinary tract infections. In patients with psoriatic arthritis, this included cholecystitis. In patients with Crohn’s disease, these included anal abscess, gastroenteritis, ophthalmic herpes zoster, pneumonia, and Listeria meningitis. In patients with ulcerative colitis, these included gastroenteritis, ophthalmic herpes zoster, pneumonia, and listeriosis.

Treatment with WEZLANA should not be initiated in patients with a clinically important active infection until the infection resolves or is adequately treated. Consider the risks and benefits of treatment prior to initiating use of WEZLANA in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur while on treatment with WEZLANA and discontinue WEZLANA for serious or clinically significant infections until the infection resolves or is adequately treated.

THEORETICAL RISK FOR VULNERABILITY TO PARTICULAR INFECTIONS

Individuals genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections from mycobacteria, Salmonella, and Bacillus Calmette-Guerin (BCG) vaccinations. Serious infections and fatal outcomes have been reported in such patients. It is not known whether patients with pharmacologic blockade of IL-12/IL-23 from treatment with ustekinumab products may be susceptible to these types of infections. Consider diagnostic testing, eg, tissue culture, stool culture, as dictated by clinical circumstances.

PRE-TREATMENT EVALUATION FOR TUBERCULOSIS (TB)

Evaluate patients for TB prior to initiating treatment with WEZLANA. Do not administer WEZLANA to patients with active tuberculosis infection. Initiate treatment of latent TB before administering WEZLANA. Closely monitor patients receiving WEZLANA for signs and symptoms of active TB during and after treatment.

MALIGNANCIES

Ustekinumab products are immunosuppressants and may increase the risk of malignancy. Malignancies were reported among patients who received ustekinumab in clinical trials. The safety of ustekinumab products has not been evaluated in patients who have a history of malignancy or who have a known malignancy. There have been reports of the rapid appearance of multiple cutaneous squamous cell carcinomas in patients receiving ustekinumab products who had risk factors for developing non-melanoma skin cancer (NMSC). All patients receiving WEZLANA, especially those >60 years or those with a history of PUVA or prolonged immunosuppressant treatment, should be monitored for the appearance of NMSC.

HYPERSENSITIVITY REACTIONS

Hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with ustekinumab products. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue WEZLANA.

POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES)

Two cases of posterior reversible encephalopathy syndrome (PRES), also known as Reversible Posterior Leukoencephalopathy Syndrome (RPLS), were reported in clinical trials. Cases have also been reported in postmarketing experience in patients with psoriasis, psoriatic arthritis and Crohn’s disease. Clinical presentation included headaches, seizures, confusion, visual disturbances, and imaging changes consistent with PRES a few days to several months after ustekinumab product initiation. A few cases reported latency of a year or longer. Patients recovered with supportive care following withdrawal of ustekinumab products.

Monitor all patients treated with WEZLANA for signs and symptoms of PRES. If PRES is suspected, promptly administer appropriate treatment and discontinue WEZLANA.

IMMUNIZATIONS

Prior to initiating therapy with WEZLANA, patients should receive all age-appropriate immunizations as recommended by current immunization guidelines. Patients being treated with WEZLANA should not receive live vaccines. BCG vaccines should not be given during treatment with WEZLANA or for one year prior to initiating treatment or one year following discontinuation of treatment. Caution is advised when administering live vaccines to household contacts of patients receiving WEZLANA because of the potential risk for shedding from the household contact and transmission to patient. Non-live vaccinations received during a course of WEZLANA may not elicit an immune response sufficient to prevent disease.

CONCOMITANT THERAPIES

In clinical studies of psoriasis, the safety of ustekinumab products in combination with other biologic immunosuppressive agents or phototherapy was not evaluated. Ultraviolet-induced skin cancers developed earlier and more frequently in mice genetically manipulated to be deficient in both IL-12 and IL-23 or IL-12 alone.

NONINFECTIOUS PNEUMONIA

Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia have been reported during post-approval use of ustekinumab products. Clinical presentations included cough, dyspnea, and interstitial infiltrates following one to three doses. Serious outcomes have included respiratory failure and prolonged hospitalization. Patients improved with discontinuation of therapy and, in certain cases, administration of corticosteroids. If diagnosis is confirmed, discontinue WEZLANA and institute appropriate treatment.

ALLERGEN IMMUNOTHERAPY

Ustekinumab products may decrease the protective effect of allergen immunotherapy (decrease tolerance) which may increase the risk of an allergic reaction to a dose of allergen immunotherapy. Therefore, caution should be exercised in patients receiving or who have received allergen immunotherapy, particularly for anaphylaxis.

MOST COMMON ADVERSE REACTIONS
  • The most common adverse reactions (≥3% and higher than that with placebo) in adults from plaque psoriasis clinical trials for ustekinumab 45 mg, ustekinumab 90 mg, or placebo were: nasopharyngitis (8%, 7%, 8%), upper respiratory tract infection (5%, 4%, 5%), headache (5%, 5%, 3%), and fatigue (3%, 3%, 2%), respectively. The safety profile in pediatric patients with plaque psoriasis was similar to that of adults with plaque psoriasis.
  • In psoriatic arthritis (PsA) trials, a higher incidence of arthralgia and nausea was observed in patients treated with ustekinumab when compared with placebo (3% vs 1% for both).
  • In Crohn’s disease induction trials, common adverse reactions (3% or more of patients treated with ustekinumab and higher than placebo) reported through Week 8 for ustekinumab 6 mg/kg intravenous single infusion or placebo included: vomiting (4% vs 3%). In the Crohn’s disease maintenance trial, common adverse reactions (3% or more of patients treated with ustekinumab and higher than placebo) reported through Week 44 for ustekinumab 90 mg subcutaneous injection or placebo were: nasopharyngitis (11% vs 8%), injection site erythema (5% vs 0%), vulvovaginal candidiasis/mycotic infection (5% vs 1%), bronchitis (5% vs 3%), pruritus (4% vs 2%), urinary tract infection (4% vs 2%) and sinusitis (3% vs 2%).
  • In the ulcerative colitis induction trial, common adverse reactions (3% or more of patients treated with ustekinumab and higher than placebo) reported through Week 8 for ustekinumab 6 mg/kg intravenous single infusion or placebo included: nasopharyngitis (7% vs 4%). In the ulcerative colitis maintenance trial, common adverse reactions (3% or more of patients treated with ustekinumab and higher than placebo) reported through Week 44 for ustekinumab 90 mg subcutaneous injection or placebo included: nasopharyngitis (24% vs 20%), headache (10% vs 4%), abdominal pain (7% vs 3%), influenza (6% vs 5%), fever (5% vs 4%), diarrhea (4% vs 1%), sinusitis (4% vs 1%), fatigue (4% vs 2%), and nausea (3% vs 2%).

Please see the accompanying WEZLANA full Prescribing Information, including Medication Guide.

INDICATIONS

WEZLANA is indicated for the treatment of patients 6 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

WEZLANA is indicated for the treatment of patients 6 years or older with active psoriatic arthritis.

WEZLANA is indicated for the treatment of adult patients with moderately to severely active Crohn’s disease.

WEZLANA is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis.

WHAT IS WEZLANA™ (ustekinumab-auub)?

WEZLANA is a prescription medicine used to treat:

  • adults and children 6 years and older with moderate to severe psoriasis who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet light alone or with pills).
  • adults and children 6 years and older with active psoriatic arthritis.
  • adults 18 years and older with moderately to severely active Crohn’s disease.
  • adults 18 years and older with moderately to severely active ulcerative colitis.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

WEZLANA is contraindicated in patients with clinically significant hypersensitivity to ustekinumab products or to any of the excipients.

STELARA® is a registered trademark of Janssen Biotech, Inc.

WEZLANA is a trademark of Amgen Inc.

References: 1. WEZLANA™ (ustekinumab-auub) prescribing information, Amgen. 2. STELARA® (ustekinumab) prescribing information, Janssen Biotech, Inc. 3. Cantin G, Liu Q, Shah B, et al. Analytical and functional similarity of the biosimilar candidate ABP 654 to ustekinumab reference product. Drugs R D. 2023;23:421-438. 4. Mihalcik L, Chow V, Ramchandani M, Hinkle B, McBride HJ, Lebrec H. Use of nonclinical toxicity studies to support biosimilar antibody development. Regul Toxicol Pharmacol. 2021;122:104912. 5. Chow V, Mytych DT, Das S, Franklin J. Pharmacokinetic similarity of ABP 654, an ustekinumab biosmiliar candidate: results from a randomized double-blind study in healthy subjects. Clin Pharmacol Drug Dev. 2023;12:863-873. 6. Blauvelt A, Papp K, Trivedi M, et al. Efficacy and safety of the biosimilar candidate ABP 654 in the treatment of moderate-to-severe plaque psoriasis: results from a phase 3, multicenter, randomized, double-blinded study. Poster Presented at: European Academy of Dermatology and Venerology 2023 Spring Symposium; May 18-20, 2023; Seville, Spain. 7. US National Library of Medicine. A study to investigate ABP 654 for the treatment of participants with moderate to severe plaque psoriasis. https://clinicaltrials.gov/study/NCT04607980. Updated December 15, 2023. Accessed October 21, 2024. 8. Data on file, Amgen; [1]; 2022. 9. US National Library of Medicine. A study to investigate interchangeability of ABP 654 for the treatment of participants with moderate to severe plaque psoriasis. https://clinicaltrials.gov/ct2/show/NCT04761627. Updated January 11, 2024. Accessed October 21, 2024. 10. Data on file, Amgen; 2023. 11. US Food and Drug Administration. Guidance for industry: scientific considerations in demonstrating biosimilarity to a reference product. www.fda.gov/ downloads/drugs/guidances/ucm291128.pdf. Accessed October 21, 2024. 12. US Food and Drug Administration. Clinical pharmacology data to support a demonstration of biosimilarity to reference product. https://www.fda.gov/media/88622/download. Accessed October 21, 2024. 13. Data on file, Amgen; [2]; 2022.

This material is for discussion and informational purposes only. WEZLANA is currently not available commercially and will be commercially available in the US no later than January 1, 2025.