Date published: 24 July, 2023
Date last updated: 24 July, 2023
Commissioning, Eye health, Medicine

Operational note: updated commissioning recommendations for medical retinal vascular medicines following the national procurement for ranibizumab biosimilars

Version 2

Purpose

Eyecare is the highest volume outpatient specialty within the NHS and the medicines used for medical retinal vascular conditions account for some of the highest cost and volume treatments used within secondary care.

Due to increasing life expectancy and an ageing population, the NHS expects that demand for medical retinal vascular treatments will continue to increase as more patients with eye disease are diagnosed and treated. Continually rising demand has also impacted ophthalmology outpatient services, worsened by the pandemic.

The intent of the procurement exercise was to support delivery of the NHS Pathway Improvement Programme through the following key objectives:

  1. Reduction in unwarranted variation
    • Reduce the number of patients who should be but are not currently treated; and reduce the number of patients who are treated, but for whom treatment is inappropriate or ineffective.
  2. Maintain clinical choice
    • Clinicians will continue to determine, in discussion with their individual patients, which medical retinal vascular treatments are clinically appropriate for them and will be able to access all available treatments (in line with national guidance).
  3. Make best use of NHS resources
    • To support the transformation of eyecare services (subject to the criteria specified in the relevant NICE technology appraisal guidance), clinicians should, in consultation with the patient, use the lowest cost treatment option where this is clinically appropriate.

Through consistently using the most clinically appropriate and cost-effective treatments and ensuring that patients receiving treatment are responding, we can drive efficiencies to support recovery and transformation in eyecare services.

This will create capacity so that patients can be seen in a timely manner and avoid permanent loss of vision, in line with the recommendations of the NHS England National Eye Care Recovery and Transformation Programme.

These commissioning recommendations outline the best value treatment choices and, if followed, will generate financial savings which can be invested in NHS services.

Anti-VEGF and intravitreal corticosteroids treatments

There are now nine licensed intravitreal anti-VEGF and corticosteroid treatments in England for medical retinal conditions, which are used for the treatment of several indications as set out in the document. These are:

  • Aflibercept (Eylea®)
  • Brolucizumab (Beovu®)
  • Dexamethasone Intravitreal implant (Ozurdex®)
  • Faricimab (Vabysmo®)
  • Fluocinolone acetonide Intravitreal implant (Iluvien®)
  • Ranibizumab (Lucentis®)
  • Ranibizumab biosimilar (Byooviz®)
  • Ranibizumab biosimilar (Ongavia®)
  • Ranibizumab biosimilar (Ximluci®)

In 2022 and 2023, three ranibizumab biosimilars were licensed, (Ongavia®, Byooviz® and Ximluci®). Equivalent safety and efficacy to the reference product ranibizumab (Lucentis®) has been confirmed in phase three clinical trials in eyes with treatment naïve neovascular AMD.

Ongavia® from Teva was the first licensed biosimilar to launch for use in England, in 2022. A national procurement for the supply of additional ranibizumab was published in January 2023 to capture the two new market entrants, Byooviz® and Ximluci® that are available from 1 April 2023.

Bevacizumab (Avastin®) at present only has a UK market authorisation for non-ophthalmology indications.

If used in any of the indications listed within these commissioning recommendations, it will be considered as ‘off-label’ use by the Medicines and Healthcare products Regulatory Agency (MHRA) and requires pre-requisites to be met. (See MHRA’s, note 14 ‘Guidance on the hierarchy for the use of unlicensed medicines’, which refers to ‘off-label’ use).

Off-label use of licensed medicines is out of scope and not included in the commissioning recommendations.

It is for the prescribing clinician and patient to determine together which treatment is clinically appropriate for an individual, based upon the specific needs of the patient and relevant NICE technology appraisal guidance for each indication.

These commissioning recommendations do not restrict a clinician’s ability to make the most appropriate decision for an individual patient through shared decision making, taking account of the patient’s needs and wishes.

Reviewing existing treatment, considering alternatives, counselling, and consenting patients to change to a different treatment will require additional time.

Ophthalmic services will need to agree with their commissioners the optimal approach to implementation of the commissioning recommendations, balancing the needs of the patients and resources available.

Treatment options

According to NICE technology appraisal guidance, ranibizumab (TA155), aflibercept (TA294), brolucizumab (TA672) and faricimab (TA800) are all suitable options for the treatment of wet AMD when used in accordance with the criteria outlined in the relevant NICE technology appraisal guidance.

This includes only treating patients with visual acuity between 6/12 and 6/96 and if patients and their clinicians consider more than one treatment to be suitable, they should choose the least expensive option.

NICE guidance on wet AMD (NG82) acknowledges that anti-VEGF treatment in patients with better visual acuity of 6/12 is clinically effective and may be cost effective depending on the treatment used.

As NG82 recommendations are not mandatory for commissioners, the use of anti-VEGFs in patients with visual acuity better than 6/12 is outside the scope of this document. If there is a local requirement, we recommend clinicians consult with their commissioners to assess the feasibility of using anti-VEGFs outside the mandatory commissioning requirements.

Treatment selection

For patients commencing treatment for wet AMD:

  • Subject to the criteria specified in the relevant NICE technology appraisal guidance, clinicians should consider ranibizumab biosimilar where this is clinically appropriate and there is capacity to do so.
  • If ranibizumab biosimilar is contra-indicated or not clinically appropriate for the specific patient, or if there are specific clinical considerations (such as non-responder to ranibizumab in fellow eye previously, subretinal bleed >50% of lesion, idiopathic polypoidal choroidal vasculopathy [PCV]) then, subject to the criteria specified in the relevant NICE technology appraisal guidance, clinicians should consider aflibercept, brolucizumab or faricimab.

Reviewing new treatment

Following the three months loading phase, treatment should continue as per the summary of product characteristics (SMPC).

For patients who have a suboptimal response, clinicians should consider either stopping treatment or changing to an alternative anti-VEGF.

If initial treatment selected was ranibizumab biosimilar, clinicians should consider changing to aflibercept, brolucizumab or faricimab.

Reviewing current treatment

For patients already prescribed an anti-VEGF for the treatment of wet AMD:

  • Subject to the criteria specified in the relevant NICE technology appraisal guidance, clinicians should consider reviewing patients currently prescribed ranibizumab (Lucentis®) to assess suitability to change to ranibizumab biosimilar.

Discontinuing treatment

NICE guidance on wet age-related macular degeneration (NG 82) recommends that treatment be continued only in people who maintain an adequate response to therapy.

Criteria for permanent discontinuation should include persistent deterioration in visual acuity and the identification of anatomical changes in the retina that indicate an inadequate response to therapy despite an optimally delivered treatment regimen.

Treatment with an anti-VEGF should be stopped if the eye develops late AMD (wet inactive) with no prospect of functional improvement or hypersensitivity to an anti-VEGF.

Extra guidance for discontinuing treatment

Reports by key opinion leaders:

Diabetic macular oedema (DMO)

Treatment options

NICE guidance recommends ranibizumab (TA237), aflibercept (TA346), faricimab (TA799) and brolucizumab (TA820) as suitable options for the treatment of diabetic macular oedema (DMO) when used in line with the criteria specified in the relevant NICE technology appraisal guidance.

If patients and their clinicians consider both ranibizumab, aflibercept, faricimab and brolucizumab to be suitable treatments, the least costly should be used.

Treatment selection

For patients commencing treatment for DMO:

  • Subject to the criteria specified in the relevant NICE technology appraisal guidance, clinicians should consider ranibizumab biosimilar where this is clinically appropriate and there is capacity to do so.
  • If ranibizumab biosimilar is contra-indicated or not clinically appropriate for the specific patient then, subject to the criteria specified in the relevant NICE technology appraisal guidance, clinicians should then consider aflibercept, faricimab or brolucizumab, dexamethasone or fluocinolone.

Reviewing new treatment

Following the loading phase, treatment should continue as per the SMPC.

For patients with suboptimal response, clinicians should consider changing to alternative anti-VEGF.

If initial treatment selected was ranibizumab biosimilar, clinicians should consider changing to either aflibercept, faricimab or brolucizumab, dexamethasone or fluocinolone.

Reviewing current treatment

For patients already prescribed an anti-VEGF for the treatment of DMO:

  • Subject to the criteria specified in the relevant NICE technology appraisal guidance, clinicians should consider reviewing patients currently prescribed ranibizumab (Lucentis®) to assess suitability for a change to ranibizumab biosimilar.
  • We do not recommend changing to ranibizumab biosimilar where patients are currently prescribed aflibercept in this condition.

Alternative/additional therapy

NICE guidance recommends fluocinolone acetonide intravitreal implant (TA301) as a suitable option for treating chronic diabetic macular oedema, and dexamethasone intravitreal implant (TA824) as a suitable option for treating diabetic macular oedema after an inadequate response to prior therapy or where ongoing treatment burden is a concern, irrespective of whether the patient has a phakic or pseudophakic lens.

When to consider intra-vitreal steroids (dexamethasone and fluocinolone acetonide)

If anti-VEGF treatment is contra-indicated or does not achieve a sufficient response (despite an appropriate injection frequency and regular monitoring), then intravitreal corticosteroid implants (dexamethasone intravitreal implant or fluocinolone acetonide intravitreal implant) should be considered (assuming the patient meets NICE guidance criteria TA 301 and TA 824, and there are no contra-indications to steroid usage).

Equally, patients may achieve good efficacy with anti-VEGF, but the frequency of repeated injections may not be tolerable for the patient due to individualised patient factors. In this last scenario, intravitreal steroids, with their potentially longer duration of action, may be useful.

The two main reasons for considering intravitreal steroid therapy for a patient previously treated with anti-VEGF are:

  • inadequate efficacy with anti-VEGF
  • intolerable anti-VEGF treatment burden.

One approach is to consider a change to intravitreal steroid after six months of anti-VEGF therapy based on the efficacy of therapy at this time-point and then to consider again a change to intravitreal steroid after two years of anti-VEGF therapy based on treatment burden at this stage.

A consensus document is published with more detail of this approach, together with supporting data:

Intra-vitreal steroid therapy may also be the first-line option for some patients where anti-VEGF agents are contraindicated or not available.

Myopic choroidal neovascularisation (CNV)

Treatment options

NICE guidance states that ranibizumab (TA298) and aflibercept (TA486) are both suitable options for the treatment of CNV when used in line with the criteria specified in the relevant NICE technology appraisal guidance.

If patients and their clinicians consider both ranibizumab and aflibercept to be suitable treatments, the least costly should be used.

Treatment selection

For patients commencing treatment for CNV:

  • Subject to the criteria specified in the relevant NICE technology appraisal guidance, clinicians should consider ranibizumab biosimilar where this is clinically appropriate and there is capacity to do so.
  • If ranibizumab biosimilar is contra-indicated or not clinically appropriate for the specific patient then, subject to the criteria specified in the relevant NICE technology appraisal guidance, clinicians should then consider aflibercept.

Reviewing new treatment

Following the two months loading phase, for patients with suboptimal response, clinicians should consider changing to alternative anti-VEGF. If initial treatment selected was ranibizumab biosimilar, consider changing to aflibercept.

Reviewing current treatment

For patients already prescribed an anti-VEGF for the treatment of CNV

  • Subject to the criteria specified in the relevant NICE technology appraisal guidance, clinicians should consider reviewing patients currently prescribed ranibizumab (Lucentis®) to assess suitability for a change to ranibizumab biosimilar.

Discontinuing treatment

The schedule for monitoring should be determined by the treating physician and should be discontinued if the patient is not benefiting from continued treatment.

Central retinal vein occlusion (CRVO)

Treatment options

NICE guidance states that dexamethasone intravitreal implant (TA229), ranibizumab (TA283) and aflibercept (TA305) are all suitable options for the treatment of CRVO when used in line with the criteria specified in the relevant NICE technology appraisal guidance.

If patients and their clinicians consider all treatments to be suitable options the least costly should be used.

Treatment selection

For patients commencing treatment for CRVO:

  • Subject to the criteria specified in the relevant NICE technology appraisal guidance, clinicians should consider ranibizumab biosimilar where this is clinically appropriate and there is capacity to do so.
  • If ranibizumab biosimilar is contra-indicated or not clinically appropriate for the specific patient then, subject to the criteria specified in the relevant NICE technology appraisal guidance, clinicians should then consider aflibercept or dexamethasone intravitreal implant.

Reviewing new treatment

Following the three months loading phase, for patients with suboptimal response to ranibizumab biosimilar, consider changing to aflibercept or dexamethasone intravitreal implant where clinically appropriate subject to the criteria specified in the relevant NICE technology appraisal guidance.

Reviewing current treatment

For patients already prescribed an anti-VEGF treatment for CRVO:

  • Subject to the criteria specified in the relevant NICE technology appraisal guidance, clinicians should consider reviewing patients currently prescribed ranibizumab (Lucentis®) to assess suitability for a change to ranibizumab biosimilar.
  • We do not recommend changing to ranibizumab biosimilar where patients are currently prescribed aflibercept in this condition.

Discontinuing treatment

If no improvement in visual acuity over the course of the first three injections is observed, cessation of treatment may be considered, and it is recommended after six injections.

Branch retinal vein occlusion (BRVO)

Treatment options

NICE guidance states that ranibizumab (TA283), aflibercept (TA409) and dexamethasone intravitreal implant (TA229) are suitable treatment options for BRVO. If patients and their clinicians consider both ranibizumab and aflibercept to be suitable treatments, the least costly should be used.

Treatment selection

For patients commencing treatment for BRVO:

  • Subject to the criteria specified in the relevant NICE technology appraisal guidance, clinicians should consider ranibizumab biosimilar where this is clinically appropriate and there is capacity to do so.
  • If ranibizumab biosimilar is contra-indicated or not clinically appropriate for the specific patient then, subject to the criteria specified in the relevant NICE technology appraisal guidance, clinicians should consider either aflibercept or dexamethasone intravitreal implant.

Reviewing new treatment

Following the three months loading phase, for patients with suboptimal response to ranibizumab biosimilar, consider changing to either aflibercept or dexamethasone intravitreal implant where clinically appropriate, subject to the criteria specified in the relevant NICE technology appraisal guidance.

Reviewing current treatment

For patients already prescribed treatment for BRVO:

  • subject to the criteria specified in the relevant NICE technology appraisal guidance, clinicians may wish to consider reviewing patients currently prescribed ranibizumab (Lucentis®) to assess suitability for a change to ranibizumab biosimilar.
  • We do not recommend changing to ranibizumab biosimilar where patients are currently prescribed aflibercept in this condition.

Discontinuing treatment

If no improvement in visual acuity over the course of the first three injections is observed, cessation of treatment may be considered, and it is recommended after six injections.

Further considerations

Monitoring outcomes

Due to the risks of permanent loss of vision in retinal conditions treated by intravitreal injections, and the risk for sight-threatening adverse events from the injection or medication, it is crucial that clinicians collaborate with commissioners and trust leaders to ensure appropriate regular quality and safety monitoring reported using an agreed set of key performance indicators (KPIs).

Significant safety events must be reported via the local incident reporting system so that these can be captured both locally and nationally via the National Reporting Learning System.

For new drugs, MHRA encourages the reporting of ALL suspected reactions via the Black Triangle Scheme as part of post-marketing surveillance.

The Royal College of Ophthalmologists is currently conducting an audit for wet AMD which supports improvement in quality of care which is an important quality assurance measure. Further information can be found at AMD Audit Clinical Data Set.pdf (nodaudit.org.uk).

The first report of the National Ophthalmology Database Audit for Age-related Macular Degeneration was published in February 2023.

Compounding units

Where the medicine is only presented in a vial (for example faricimab or biosimilar ranibizumab), clinicians will need to draw up the required dose of medicine into a syringe at the point of administration.

Aseptic compounding services should be avoided due to the ongoing constraint in capacity (commercial and NHS). Local services will need to consider how to take account of the need to draw up the drug rather than using a prefilled syringe.

Reviewing current treatments

Adequate allocation of resources is recommended to ensure sufficient clinic staff and time are available to manage the increase in patient contact time to counsel and consent patients when changing treatments.

A cost calculator has been developed that provides guidance to clinicians and commissioners on the potential resource impact for treatments being considered for a local population. Please contact scm.procurements@nhs.net for a copy.

Managed onboarding

Due to previously limited stocks of ranibizumab an onboarding approach was used. However, as there are now several options for obtaining ranibizumab biosimilars, trusts can purchase the medicines through their normal procurement processes.

Resources

NHS England’s What is a biosimilar medicine? guidance provides information for key clinical and non-clinical stakeholders about the role of biosimilar medicines in the NHS in England to support the safe, effective, and consistent use of all biological medicines, including biosimilar medicines, to the benefit of patients.

Several resources are also available to support trusts and healthcare professionals to use the biosimilars:

Summary of anti-VEGF and intravitreal corticosteroids via the NHS national framework agreement for England

Aflibercept

Brand name: Eylea®

  • Strength:
    • 40 mg/ml solution for injection in a vial
    • 40 mg/ml solution for injection in a pre-filled syringe
  • Pack size: 1

Brolucizumab

Brand name: Beovu®

  • Strength:
    • 120 mg/ml for injection in a pre-filled syringe
  • Pack size: 1

Dexamethasone intravitreal implant

Brand name: Ozurdex®

  • Strength:
    • 700 microgram implant
  • Pack size: 1

Faricimab

Brand name: Vabysmo®

  • Strength:
    • 120 mg/ml solution for injection in a vial
  • Pack size: 1

Flucinolone acetonide intravitreal implant

Brand name: Iluvien®

  • Strength:
    • 190 microgram implant
  • Pack size: 1

Ranibizumab

Brand name: Byooviz®

  • Strength:
    • 10 mg solution for injection in a vial
  • Pack size: 1

Brand name: Lucentis®

  • Strength:
    • 10 mg solution for injection in a vial
    • 10 mg solution for injection in a pre-filled syringe
  • Pack size: 1

Brand name: Ongavia®

  • Strength:
    • 10 mg solution for injection in a vial
  • Pack size: 1

Brand name: Ximluci®

  • Strength:
    • 10 mg solution for injection in a vial
  • Pack size: 1

Publication reference: PRN00087

Date published: 24 July, 2023
Date last updated: 24 July, 2023