Licensed indications

Byooviz, Ongavia and Ximluci are licensed in adults for the treatment of:

• neovascular (wet) age-related macular degeneration (AMD)
• visual impairment due to diabetic macular oedema (DMO)
• proliferative diabetic retinopathy (PDR)
• visual impairment due to macular oedema secondary to retinal vein occlusion (branch RVO or central RVO)
• visual impairment due to choroidal neovascularisation (CNV)

These are the same licensed indications, in adults, as the originator product Lucentis

Evidence supporting safety and efficacy

Byooviz

A randomised trial in 705 patients with untreated neovascular age-related macular degeneration, showed that the ranibizumab biosimilar (Byooviz) was clinically equivalent to the reference product when 0.5mg was given via intravitreal injection every 4 weeks for up to 12 months.

The first primary outcome was the change from baseline BCVA at 8 weeks. Equivalence was defined as a margin of 3 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. The second primary outcome was the change from baseline in central subfield thickness (CST) at 4 weeks. Equivalence was defined as a margin of 36 micrometres.

Ranibizumab biosimilar (Byoovia) and reference ranibizumab (Lucentis) showed mean improvements of +6.2 and +7.0 ETDRS letters respectively – an adjusted treatment difference of 0.8 letters with a 95% confidence interval ranging between -1.8 to +0.2 letters. For CST, the ranibizumab biosimilar (Byoovia) and reference ranibizumab (Lucentis) showed mean changes from baseline of -108 micrometres and -100 micrometres respectively. This was an adjusted treatment difference of 8 micrometres, with a 95% confidence interval ranging between -19 micrometres to +3 micrometres. These findings support the equivalent efficacy of the ranibizumab biosimilar (Byooviz) to the reference product.

The safety profile and immunogenicity of ranibizumab biosimilar (Byooviz) and the reference product were similar.

Ongavia

A randomised trial in 477 patients with newly diagnosed, treatment-naïve neovascular age-related macular degeneration, showed that the ranibizumab biosimilar (Ongavia) was clinically equivalent to the reference product when 0.5mg was given by intravitreal injection every 4 weeks for up to 12 months.

The primary outcome was change from baseline BCVA at 8 weeks before the third injection was given. Equivalence was defined as a margin of 3 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. The assessment of BCVA at 8 weeks has been endorsed by the regulatory authorities as being appropriate.

In the European relevant population of 429 patients, ranibizumab biosimilar (Ongavia) and reference ranibizumab (Lucentis) showed mean improvements of +5.2 and +6.0 ETDRS letters respectively – an adjusted difference of 0.7 letters with a 95% confidence interval ranging between -2.3 to +0.9 . These results support ranibizumab biosimilar (Ongavia) equivalence to the reference product.

The frequency and type of ocular adverse effects and immunogenicity were similar.

Ximluci

A randomised trial in 582 patients with untreated neovascular age-related macular degeneration, showed that the ranibizumab biosimilar (Ximluci) was clinically equivalent to the reference product when 0.5mg was given via intravitreal injection every 4 weeks for up to 12 months. The full report is due to be published later in 2023.

The primary outcome was the change from baseline BCVA at 8 weeks using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Equivalence was defined as a margin of 3.5 letters.

The ranibizumab biosimilar (Ximluci) and reference ranibizumab (Lucentis) showed mean improvements of +4.57 and +6.37 ETDRS letters respectively – a difference of 1.79 letters with a 95% confidence interval ranging between -3.14 to -0.45. These results support ranibizumab biosimilar (Ximluci) equivalence to the reference product.

The safety profile and immunogenicity of ranibizumab biosimilar (Ximluci) and the reference product were similar.

NICE recommendations

NICE recommends ranibizumab as a treatment option for most of the biosimilar licensed indications but does not differentiate between the different licensed anti-VEGF treatments available.

NICE guidance on treatment of age-related macular degeneration published in 2018 states that no clinically significant differences in effectiveness and safety of aflibercept, bevacizumab and ranibizumab were seen in the trials considered, so comparable regimes will be more cost effective if the agent has lower net acquisition, administration and monitoring costs.

For treatment of diabetic macular oedema, visual impairment caused by macular oedema secondary to retinal vein occlusion and choroidal neovascularisation associated with pathological myopia, NICE recommends ranibizumab as a treatment option.

None of the available anti-VEGF medicines are currently recommended by NICE for the treatment of diabetic retinopathy. NICE guidance on the management and monitoring of diabetic retinopathy is currently in development (Publication expected January 24)

Where NICE has already recommended the originator biological medicine, the same guidance will apply to the biosimilar. Biosimilars do not require a separate or additional Technology Appraisal.

Update history