The licence and supporting evidence for ustekinumab biosimilars

Licensed indications

Ustekinumab biosimilars available for use within the NHS framework are approved for all reference product (Stelara) indications.

Preparing to use ustekinumab biosimilar (SPS page) provides further information on introducing biosimilar ustekinumab in your organisation.

Evidence supporting safety and efficacy

The clinical efficacy, safety profile and immunogenicity of ustekinumab biosimilars and Stelara, the reference product, are similar. For each product, two comparative studies were submitted to support the biosimilar licence application. Further details are available in the public assessment reports.

Otulfi (Fresenius Kabi)

A published randomised, double-blind, efficacy and safety study in 392 patients with moderate to severe plaque psoriasis demonstrated similarity in clinical efficacy between Otulfi (ustekinumab biosimilar, FYB202) and ustekinumab reference product. The mean psoriasis area and severity index (PASI) improvement for Otufli vs. reference product was 79.5% vs. 76.2% (95% CI for least mean square difference: −0.90%, 7.44%) after 12 weeks. Safety profiles remained comparable between Pyzchiva and reference product.

In a published randomised, double-blind, single dose pharmacokinetic study 486 healthy adults received 45mg Otufli (ustekinumab biosimilar, FYB202), the EU or US reference product (Stelara). The study demonstrated primary outcomes of pharmacokinetic parameters  within pre-specified equivalence margins. Safety and immunogenicity were comparable between products.

Pyzchiva (Sandoz)

A published randomised, double-blind, efficacy and safety study in 503 patients with moderate to severe plaque psoriasis demonstrated similarity in clinical efficacy between Pyzchiva (ustekinumab biosimilar, SB17) and ustekinumab reference product. The mean PASI improvement for Pyzchiva vs. reference product was 85.7% vs. 86.3% (90% CI for the least mean square difference: −3.34%, 1.93%) after 12 weeks. Safety profiles remained comparable between Pyzchiva and reference product.

In a published randomised, double-blind, single dose pharmacokinetic study 201 healthy adults received 45mg Pyzchiva (ustekinumab biosimilar, SB17), the EU or US reference product (Stelara). The study demonstrated primary outcomes of pharmacokinetic parameters  within pre-specified equivalence margins. Safety and immunogenicity were comparable between products.

Steqeyma (Celltrion)

A published randomised, double-blind, efficacy and safety study in 509 patients with moderate to severe plaque psoriasis demonstrated similarity in clinical efficacy between Steqeyma (ustekinumab biosimilar, CT-P43) and ustekinumab reference product. The mean PASI improvement for Steqeyma vs. reference product was 78.3% vs. 77.3% (95% CI for the least mean square difference: -2.29%, 4.16%) after 12 weeks. Safety profiles remained comparable between Steqeyma and reference product.

In a unpublished randomised, double blind, single dose pharmacokinetic study 241 health adults received 45mg Steqeyma (ustekinumab biosimilar, CT-P43), the EU or US reference product (Stelara). The study initially suggested higher exposure with Steqeyma compared to EU reference product. However, post hoc analyses showed this was related to an aggregation of effects related to protein content of Steqeyma compared to the EU reference product, immunogenicity and increased clearance associated with increased bodyweight. Bioequivalence was demonstrated when these factors were corrected for.

In a second unpublished randomised, double-blind, single dose pharmacokinetic study 325 healthy adults received 45mg Steqeyma (ustekinumab biosimilar, CT-P43), the EU or US reference product (Stelara). A post-hoc pooled analysis of the two studies suggested the totality of pharmacokinetic data demonstrated Steqeyma was equivalent to the EU reference product.

Uzpruvo (Stada, Thornton & Ross)

A published randomised, double-blind, efficacy and safety study in 581 patients with moderate to severe plaque psoriasis demonstrated similarity in clinical efficacy between Uzpruvo (biosimilar ustekinumab, AVT04) and ustekinumab reference product. The mean PASI improvement for Uzpruvo vs. reference product was 87.3% vs. 86.8% (90% CI for the least mean square difference: −2.14%, 3.01%) after 12 weeks. Safety profiles remained comparable between Uzpruvo and reference product.

In a published randomised, double-blind, single dose pharmacokinetic study 298 healthy adults received 45mg Uzpruvo (biosimilar ustekinumab; AVT04), EU or US reference product (Stelara). After pre-specified protein content normalisation, the study demonstrated primary outcomes of pharmacokinetic parameters within pre-specified equivalence margins. Safety and immunogenicity were comparable between products.

Wezenla (Amgen)

A randomised, double blind, efficacy and safety study of 563 patients with moderate to severe plaque psoriasis demonstrated similarity in clinical efficacy between Wezenla (biosimilar ustekinumab, ABP654) and ustekinumab reference product. The mean PASI improvement was 81.9% (90% CI for least mean square difference: −2.63%, 2.90%) for both Wezenla and reference product after 12 weeks. Safety profiles remained comparable between Wezenla and reference product. Switching from the reference product to Wezenla did not change efficacy or safety.

In a published randomised, double-blind, single dose pharmacokinetic study 238 healthy adults received 90mg Wezenla (biosimilar ustekinumab, ABP654), the EU or US reference product (Stelara). The study demonstrated primary outcomes of pharmacokinetic parameters within pre-specified equivalence margins. Safety and immunogenicity were comparable between products.

Yesintek (Biosimilar Collaborations Ireland)

A published randomised, double blind, efficacy and safety study of 324 patients with moderate to severe plaque psoriasis demonstrated similarity in clinical efficacy between Yesintek (biosimilar ustekinumab, Bmab 1200) and ustekinumab reference product. The mean PASI improvement for Yesintek vs. reference product was 79.9% vs. 80.5% (95% CI: −1.69%, 3.02%) after 12 weeks. Safety profiles remained comparable between Yesintek and reference product.

In a published randomised, double-blind, single dose pharmacokinetic study 258 healthy adults received 45mg Yesintek (ustekinumab biosimilar, Bmab 1200), the EU or US reference product (Stelara). The study demonstrated primary outcomes of pharmacokinetic parameters within pre-specified equivalence margins. Safety and immunogenicity were comparable between products.

Differences between brands

Comparisons of excipients and shelf life between ustekinumab biosimilars and the reference product (Stelara).

Diluent

Intravenous (IV) formulations must be diluted prior to use with sodium chloride 0.9%. Pyzchiva can be diluted with either sodium chloride 0.45% or 0.9%.

Sodium content

Most of the sodium burden will come from the diluent used to prepare the IV formulation.

Undiluted IV formulation

All available ustekinumab biosimilars are essentially ‘sodium free’, in other words they contain less than 1mmol of sodium per dose.

Assessing the clinical impact of sodium content in medicines (SPS page) provides further information on sodium in medicines.

Subcutaneous formulation

All available ustekinumab biosimilars for subcutaneous administration can be considered sodium free.

Other excipients of interest

There are no significant differences in relation to excipients of interest between the reference product and the currently approved biosimilar products.

Histidine

Also known as L-histidine; the terms can be used interchangeably.

Latex

All available biosimilar products are latex free.

The needle cover of Stelara pre-filled syringes and pre-filled pens is manufactured from a derivative of latex (dry natural rubber).

Needle characteristics

All ustekinumab preparations use small gauge needles, 27G (0.413mm) or 29G (0.337mm), and the small differences are unlikely to cause a difference in practice.

The following ustekinumab subcutaneous products have 29G needles:

• Otulfi
• Pyzchiva
• Uzpruvo
• Yesintek

The following ustekinumab subcuteanous products have 27G needles:

• Stelara
• Steqeyma
• Wezenla

Storage and stability

All ustekinumab products should be stored in a refrigerator (2°C to 8°C).

Following dilution

Following dilution outside of controlled and validated aseptic conditions, ustekinumab biosimilars and reference product should be used immediately.

Subcutaneous formulations

The following biosimilar can be stored within their expiry date at temperatures up to 30°C, for a single period of up to 30 days:

• Otulfi, Pyzchiva, Uzpruvo, Wezenla and Yesintek

The following biosimilar can be stored within their expiry date at temperatures up to 30°C, for a single period of up to 31 days:

• Steqeyma

Administration

All available biosimilar products should be infused over at least one hour when administered intravenously.

Update history