Licensed indications

Biosimilar ustekinumab products are not approved for use in ulcerative colitis, as this indication is currently subject to legal challenge. Ustekinumab biosimilars (Pyzchiva, Steqeyma, Uzpruvo, Wezenla) are approved for all other reference product (Stelara) indications. Refer to the individual summary of medicinal product characteristics for further information.

Formulations

Not all biosimilar products will be in the same formulation or presentations as the reference product, at least initially.

On launch Uzpruvo (Stada, Thornton & Ross) will not be available as a vial for infusion. An alternative ustekinumab product is required for the initial intravenous dose required in Crohn’s disease.

On launch Uzpruvo (Stada, Thornton & Ross), Pyzchiva (Sandoz) and Steqeyma (Celltrion) will not be available as vials for injection. An alternative ustekinumab product is required for paediatric patients less than 60kg who need to receive less than a 45mg dose.

No ustekinumab biosimilars yet have a licensed pre-filled pen formulation.

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.

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 psoriasis area and severity index (PASI) improvement for Pyzchiva vs. reference product was 85.7% vs. 86.3% (90% CI: −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: -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: −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: −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.

Differences between brands

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

Diluent

Intravenous (IV) formulations must be further diluted prior to use:

• Stelara – sodium chloride 0.9%
• Wezenla – sodium chloride 0.9%
• Steqeyma – sodium chloride 0.9%
• Pyzchiva – 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

Stelara, Steqeyma, Pyzchiva and Wezenla are essentially ‘sodium free’, in other words they contain less than 1mmol of sodium per dose.

Considering sodium content of medicines provides further information on sodium in medicines.

Subcutaneous formulation

All ustekinumab products for subcutaneous administration can be considered sodium free.

• Stelara and Wezenla vials for injection do not list sodium as an excipient
• Stelara, Steqeyma, Pyzchiva, Uzpruvo and Wezenla pre-filled syringes do not list sodium as an excipient

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 biosimilar products; Pyzchiva, Steqeyma, Uzpruvo and Wezenla 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 products have 29G needles:

• Pyzchiva pre-filled syringe
• Uzpruvo pre-filled syringe

The following ustekinumab products have 27G needles:

• Stelara pre-filled syringe and pre-filled pen
• Steqeyma pre-filled syringe
• Wezenla pre-filled syringe

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

• Stelara, Pyzchiva, Uzpruvo and Wezenla pre-filled syringes
• Wezenla vials for injection

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

• Steqeyma pre-filled syringes

Remove Stelara vials for subcutaneous administration from the refrigerator just before administration.

Update history