Scope
All denosumab 120mg biosimilar products included in the NHS Framework awards are covered within this article.
NHS Trusts should be guided on the choice of biosimilar products by the NHS Framework awards.
Licensed indications
Denosumab 120 mg biosimilars are approved for all reference product (Xgeva) indications.
Formulations
In line with the reference product presentations (Xgeva), all denosumab 120 mg biosimilars on the NHS Framework awards will be available as vials, while Bomyntra will also be offered as a pre-filled syringe.
Vials
- Bomyntra (Fresenius Kabi)
- Enwylma (Zentiva)
- Jubereq (Accord Healthcare)
- Osenvelt (Celltrion Healthcare)
- Yaxwer (Gedeon Richter)
Pre-filled syringe
- Bomyntra (Fresenius Kabi)
Evidence supporting safety and efficacy
All denosumab 120 mg biosimilars authorised in the UK have demonstrated high similarity to the reference product, Xgeva. Laboratory studies confirm the active substance in the denosumab biosimilars is highly similar to the reference product in terms of structure, purity and biological activity. Studies have also shown that denosumab biosimilars produce similar levels of the active substance in the body to those seen with Xgeva.
Extrapolation of data from other indications
Denosumab 120mg is licensed for the:
- prevention of skeletal-related events in adults with advanced cancers involving bone
- treatment of unresectable or high-morbidity giant cell tumours of bone
Denosumab has the same mechanism of action for these conditions and for osteoporosis. The comparative clinical data used to support biosimilarity was generated in people with osteoporosis, as the MHRA considers it scientifically justified to extrapolate the evidence generated in the osteoporosis studies to the oncology indications. No clinically meaningful differences between each denosumab biosimilar and Xgeva were identified. Details of the clinical studies which support licensing are available in the European public assessment reports:
Differences between brands
Comparison of excipients and shelf life between denosumab biosimilars available on the NHS Framework awards and the reference products (Xgeva).
Administration
There is no difference in the method of administration between Xgeva and the biosimilar products available on the NHS Framework awards. However, there may be differences in the presentations of products.
Vials
Xgeva and the denosumab 120mg biosimilar vials (Bomyntra, Enwylma, Jubereq, Osenvelt and Yaxwer) are available as 120mg in 1.7mL and should only be administered by a healthcare professional.
Pre-filled syringes
Xgeva and the Bomyntra pre-filled syringes differ in concentration:
- Bomyntra is available as 120 mg in 1.7 mL
- Xgeva is available as 120 mg in 1mL
Both can be administered by a patient or caregiver who has been trained in injection techniques by a healthcare professional. The first self-administration with the pre-filled syringes should be supervised by a healthcare professional. Patients should be informed of the differences in syringe design when switching to the biosimilar.
Sodium content
Xgeva and the denosumab 120mg biosimilar products available on the NHS Framework awards can be considered sodium-free.
Other excipients of interest
There are no significant differences in relation to excipients of interest between the reference products and the currently approved biosimilar products included in NHS Framework awards. Refer to the individual Summary of Product Characteristics for further information on excipients and any variations between products.
Sorbitol
Xgeva and the denosumab 120mg biosimilar products available on the NHS Framework awards contain sorbitol.
The vials contain between 78 to 79.9mg of sorbitol.
The pre-filled syringes contain 37mg sorbitol (Xgeva) or 79.9mg (Bomyntra). Prescribers should consider these differences for patients with sorbitol (fructose) intolerance.
Polysorbate 20
All denosumab 120mg biosimilar products available on the NHS Framework awards contain polysorbate 20 which may cause allergic reactions.
The vials of Bomyntra, Enwylma, Jubereq, Osenvelt, Xgeva and Yaxwer and the Bomyntra pre-filled syringe contain 0.17 mg of polysorbate 20. The Xgeva pre-filled syringe contains 0.1mg of polysorbate 20.
Phenylalanine
The Xgeva pre-filled syringes contain phenylalanine, whereas the Bomyntra pre-filled syringes do not.
Xgeva vials and all denosumab 120 mg biosimilar vials do not contain phenylalanine.
Latex
Xgeva and the denosumab 120mg biosimilar products available on the NHS Framework awards (Enwylma, Jubereq, Osenvelt and Yaxwer) are latex-free.
The presence of latex is currently unknown for Bomyntra vials and pre-filled syringes. This article will be updated as information becomes available.
Needle characteristics
A 27-gauge (0.413 mm) needle is recommended for administration of Xgeva and the denosumab 120mg products available on the NHS Framework awards. The denosumab pre-filled syringes are supplied with a 27-gauge needle.
Storage and stability
Shelf life
There is some variation in the shelf life between the denosumab 120mg vials:
- 2 years: Jubereq
- 3 years: Bomyntra, Enwylma, Yaxwer
- 3.5 years: Osenvelt
- 4 years: Xgeva
The Xgeva and Bomyntra pre-filled syringes have the same-shelf life of 3 years.
Storage
Xgeva and the denosumab 120mg biosimilar products available on the NHS Framework awards should be stored in a refrigerator (2°C to 8°C).
They can be stored within their expiry date at temperatures up to 25°C for a single period of up to 30 days. The products must be discarded if not used within 30 days.
Remove denosumab vials and pre-filled syringes for subcutaneous administration from the refrigerator before administration to allow the product to reach room temperature.
Further resources
SPS have further resources on biosimilars and biosimilar denosumab 120mg.