| Drug Name |
PYZCHIVA® (ustekinumab-ttwe) |
| Active Ingredient |
ustekinumab |
| Date of Approval |
June 28, 2024 |
| Manufacturer |
Samsung Bioepis Co., Ltd. |
| Approval Pathways and Indications |
Approval Pathway: BLA
Indication: PYZCHIVA® 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, adult patients with moderately to severely active Crohn’s disease, adult patients with moderately to severely active ulcerative colitis. |
| Therapeutic Class |
Monoclonal Antibody |
| Formulation |
45 mg/0.5 mL and 90 mg/mL pre-filled syringes for subcutaneous injection and 130 mg/26 mL (5 mg/mL) single-dose vial for intravenous infusion |
| MoA |
Ustekinumab products are human IgG1қ monoclonal antibodies that bind with specificity to the p40 protein subunit used by both the IL-12 and IL-23 cytokines. IL-12 and IL-23 are naturally occurring cytokines that are involved in inflammatory and immune responses, such as natural killer cell activation and CD4+ T-cell differentiation and activation. In in vitro models, ustekinumab products were shown to disrupt IL-12 and IL-23 mediated signaling and cytokine cascades by disrupting the interaction of these cytokines with a shared cell- surface receptor chain, IL-12Rβ1. The cytokines IL-12 and IL-23 have been implicated as important contributors to the chronic inflammation that is a hallmark of Crohn's disease and ulcerative colitis. In animal models of colitis, genetic absence or antibody blockade of the p40 subunit of IL-12 and IL-23, the target of ustekinumab products, was shown to be protective. |
| Dosing and Administration |
The psoriasis adult ubcutaneous recommended dosage for adults less than or equal to 100 kg is 45 mg administered subcutaneously initially and 4 weeks later, followed by 45 mg administered subcutaneously every 12 weeks. The psoriasis adult subcutaneous recommended dosage for adults greater than 100 kg is 90 mg administered subcutaneously initially and 4 weeks later, followed by 90 mg administered subcutaneously every 12 weeks.
The psoriasis pediatric patients (6 to 17 years old) subcutaneous recommended dosage is weight based at the initial dose, 4 weeks later, then every 12 weeks thereafter to be 45 mg if they weight in the range of 60 kg - 100 kg and 90 mg if greater than 100 kg.
For psoriatic arthritis adult, the subcutaneous recommended dosage is 45 mg administered subcutaneously initially and 4 weeks later, followed by 45 mg administered subcutaneously every 12 weeks. For patients with co-existent moderate-to-severe plaque psoriasis weighing greater than 100 kg, the recommended dosage is 90 mg administered subcutaneously initially and 4 weeks later, followed by 90 mg administered subcutaneously every 12 weeks.
The psoriatic arthritis pediatric patients (6 to 17 years old) subcutaneous recommended dosage is weight based at the initial dose, 4 weeks later, then every 12 weeks thereafter to be 45 mg if they weight greater than 60 kg - 100 kg and 90 mg if greater than 100 kg with coexistent moderate-to-severe plaque psoriasis.
The Crohn's disease and Ulcerative Colitis initial adult intravenous recommended dosage is a single intravenous infusion using weight based dosing where they will receive 260 mg (2 vials) if they weigh up to 55 kg, 390 mg (3 vials) if they weight greater than 55 kg to 85 kg, or 520 mg (4 vials) if they weight greater than 85 kg.
The Crohn's Disease and Ulcerative Colitis maintenance adult subcutaneous recommended dosage is a subcutaneous 90 mg dose 8 weeks after the initial intravenous dose, then every 8 weeks thereafter. |
| Administered by self or by HCP |
Administered by HCP |
| Place in Therapy |
PYZCHIVA® marks the third biosimilar referencing Stelara (ustekinumab) to be approved for the American market, and the biosimilar was approved with an interchangeability designation, allowing for it to be substituted for the reference product at the pharmacy level without waiting for physician approval. PYZCHIVA®'s approval follows those for Wezlana (ustekinumab-auub) in November 2023 and Selarsdi (ustekinumab-aekn) in April 2024. The FDA approved PYZCHIVA® based on comprehensive evidence, including analytical, nonclinical, and clinical data, confirming its biosimilarity to Stelara with no significant differences in safety, purity, or potency.
“The FDA approval of PYZCHIVA® as a biosimilar to Stelara is an important milestone for patients living with inflammatory conditions, as biosimilars can offer more choice and access to biologic treatments,” said Byoung In Jung, vice president and regulatory affairs team leader at Samsung Bioepis. “In addition, biosimilars have a potential to reduce the financial burden of health care systems, especially in the US where biologics account for more than 46% of the annual drug spending.”
PYZCHIVA® may cause a rare but serious condition affecting the brain called Posterior Reversible Encephalopathy Syndrome (PRES). Patients should not use PYZCHIVA® if they are allergic to the active ingredient ustekinumab, PYZCHIVA®, Stelara, or any of the inactive ingredients contained in PYZCHIVA®, have received a BCG (Bacillus Calmette and Guérin) vaccine within 1 year before, during, or 1 year following treatment, or have active tuberculosis. |
| Expected Market Launch Date |
Sandoz, the global leader in generic and biosimilar medicines, intends to launch PYZCHIVA® in the US in February 2025 |
| New Molecular Entity (NME) or Existing Formulation |
Existing Formulation |
| Expected Cost |
Data Unavailable |
| Product Discontinuation |
N/A |
| Clinical Trials |
In two multicenter, randomized, double-blind, placebo-controlled trials (Ps STUDY 1 and Ps STUDY 2) for adults with plaque psoriasis, subjects aged 18 and older with significant psoriasis involvement were enrolled. These trials demonstrated a statistically significant improvement in psoriasis severity and body surface area involvement with ustekinumab treatment compared to placebo. The UC-1 trial, focusing on ulcerative colitis, randomized 961 patients who had failed previous therapies to receive a single intravenous administration of ustekinumab (~6 mg/kg), 130 mg (lower dose), or placebo. The primary endpoint was clinical remission at Week 8, defined by specific Mayo score criteria. Secondary endpoints included clinical response, endoscopic improvement, and histologic-endoscopic mucosal improvement. A significantly greater proportion of patients treated with ustekinumab achieved clinical remission at Week 8 compared to placebo (p < 0.001). Higher clinical response rates were observed with ustekinumab compared to placebo, with a statistically significant difference (p < 0.001). Ustekinumab treatment resulted in greater endoscopic improvement compared to placebo, with the difference being statistically significant (p < 0.001). A significantly higher proportion of patients achieved combined histologic-endoscopic mucosal improvement with ustekinumab compared to placebo (p < 0.001). The data from these trials underline the efficacy of ustekinumab in achieving significant clinical outcomes in both plaque psoriasis and ulcerative colitis, with statistically significant differences favoring ustekinumab over placebo in all measured endpoints. Adverse reactions included nasopharyngitis, headache, and gastrointestinal symptoms, with low rates of infections and malignancies observed. |
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FDA Approves Biosimilar PYZCHIVA (ustekinumab-ttwe) to Be Commercialized by Sandoz in the US [news release].
Sandoz.
https://www.sandoz.com/fda-approves-biosimilar-pyzchivar-ustekinumab-ttwe-be-commercialized-sandoz-us/.
Published June 26, 2024. Accessed July 3, 2024.
PYZCHIVA (ustekinumab-ttwe) injection, for subcutaneous or intravenous use [prescribing information]. Sandoz. https://prod.cms.us.sandoz.com/sites/spare37_
sandoz_com
/files/Media%20Documents/BLA%20761373%
20and%20BLA%20761425%20PI%20MG%20and%20IFU.pdf. Updated June 2024. Accessed July 3, 2024.
Garcia R. FDA Approves Samsung Bioepis’ PYZCHIVA, a Biosimilar to Stelara. Center for Biosimilars. https://www.centerforbiosimilars.com/view/fda-approves-samsung-bioepis-pyzchiva-a-biosimilar-to-stelara . Published June 26, 2024. Accessed July 3, 2024. |