Licensed indications

Tocilizumab biosimilar (Tyenne) has the same licensed indications, for each formulation, as the reference product RoActemra. Refer to the individual summary of medicinal product characteristics for further information.

If tocilizumab is currently used for an unlicensed or off-label indication, then it will still be unlicensed or off-label if Tyenne is used instead.

Preparing to use tocilizumab biosimilar provides links to commissioning statements for unlicensed uses of tocilizumab. 

Evidence supporting safety and efficacy

The clinical efficacy, safety profile and immunogenicity of tocilizumab biosimilar (Tyenne) and the reference product are similar.

Clinical trial data

A published, double-blind, parallel-group study of 604 adults with moderately to severely active rheumatoid arthritis (RA) were randomised 1:1 to 162mg tocilizumab biosimilar or reference product via subcutaneous injection weekly for 24 weeks. The study showed evidence of therapeutic equivalence between Tyenne and RoActemra. All patients previously had an inadequate clinical response to at least one disease modifying antirheumatic drug (DMARD) and were receiving a stable dose of methotrexate.

Primary outcome

The primary outcome was the absolute mean change of Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) at 24 weeks for tocilizumab biosimilar (Tyenne) -3.53 (95% CI -3.74 to -3.32) and the reference product, -3.54 (95% CI -3.75 to -3.35).

This corresponded to a least square mean difference of 0.01 (95% CI -0.19 to 0.22) which was within the equivalence margin of ± 15% supporting clinical equivalence. The mean change of DAS28-ESR in both treatment groups is considered high and clinically relevant in RA.

Secondary outcome

The secondary outcome was the American College of Rheumatology (ACR) 20 response criteria; a composite measure defined as an improvement of 20% in three of five criteria. ACR20, at 24 weeks, response for tocilizumab biosimilar (Tyenne) was 80.75% compared to 84.77% for the reference product.

Corresponding to a difference of -3.94% (95% CI -9.97 to 2.11), which was within the equivalence margin of ± 15%.

Safety and immunogenicity data

Frequency of severe side effects were similar between Tyenne and the reference product (9.3% vs 9.9%). However, injection site reactions occurred more frequently with Tyenne (11.3%) than the reference product (4.6%) after 24 weeks. This difference was reduced after 63 weeks, the frequency of injection site reactions reported as 12.3% and 8% for Tyenne and the reference product, respectively.

A small difference in immunogenicity was observed but was not considered to pose a clinical issue.

Pharmacokinetic trial data

Three comparative pharmacokinetic studies were conducted to demonstrate pharmacokinetic similarity between Tyenne and RoActemra.

One study compared single dose subcutaneous administration of Tyenne against the reference product in healthy subjects, and the other a single intravenous infusion.

Both pivotal studies showed similar pharmacokinetic parameters between Tyenne and reference product, demonstrating pharmacokinetic similarity. The third study demonstrated equivalence between Tyenne pre-filled pens and pre-filled syringes.

Differences between brands

Comparison of the excipients and shelf life of the Tyenne and the reference product (RoActemra) formulations.

Diluent

• RoActemra (IV formulation) – sodium chloride 0.9%
• Tyenne (IV formulation) – 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

Tyenne contains less sodium per vial than RoActemra. Doses of both products up to 800mg are essentially ‘sodium free’, in other words they contain less than 1mmol sodium per dose.

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

Subcutaneous formulation

• RoActemra – sodium free
• Tyenne – essentially ‘sodium free’

Other excipients of interest

Sucrose

RoActerma concentrate for solution is the only product to contain sucrose.

Sorbitol or citrate

None of the products contain sorbitol or citrate.

Polysorbate 80

All tocilizumab products contain polysorbate 80.

Storage and stability

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

Undiluted vials

• Tyenne – vials can be stored at temperatures up to a maximum of 25°C for a single period of up to 28 days, the vial must be protected from light and discarded if not used within the 4 week period
• RoActerma – no additional stability data

Following dilution

Following dilution, tocilizumab biosimilar and reference product should be used immediately. Additional stability data is available for tocilizumab: 

• Tyenne – prepared in controlled and validated aseptic conditions can be stored for 24 hours at temperatures up to 30°C.
• RoActemra – prepared in controlled and validated aseptic conditions can be stored for 24 hours at temperatures up to 30°C and for 14 days in a refrigerator at 2°C to 8°C.

Subcutaneous formulations

Individual pens may be stored at room temperature under the following conditions:

• Tyenne can be stored at temperatures up to 25°C for up to 14 days.
• RoActemra can be stored at temperatures up to 30°C for up to 14 days.

NICE recommendations

Where NICE has already recommended the reference biological medicine, the same guidance will apply to the biosimilar. Biosimilars do not require a separate or additional Technology Appraisal (TA). Preparing to use tocilizumab biosimilar provides links to all NICE TAs relating to tocilizumab.