Faricimab for treating diabetic macular oedema

Evidence-based recommendations on faricimab (Vabysmo) for diabetic macular oedema in adults.

# Recommendations
Faricimab is recommended as an option for treating visual impairment due to diabetic macular oedema in adults, only if:
the eye has a central retinal thickness of 400 micrometres or more at the start of treatment
the company provides faricimab according to the commercial arrangement.
If patients and their clinicians consider faricimab to be 1 of a range of suitable treatments (including aflibercept and ranibizumab), choose the least expensive treatment. Take account of administration costs, dosage, price per dose and commercial arrangements.
These recommendations are not intended to affect treatment with faricimab that was started in the NHS before this guidance was published. People having treatment outside these recommendations may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.
Why the committee made these recommendations
Diabetic macular oedema is usually treated first with aflibercept or ranibizumab, which are already recommended by NICE for treating diabetic macular oedema if the eye has a central retinal thickness of 400 micrometres or more when treatment starts. Faricimab is another treatment option that works in a similar way.
Evidence from clinical trials shows that faricimab is as effective as aflibercept. An indirect comparison of faricimab with ranibizumab also suggests similar clinical effectiveness.
A cost comparison suggests faricimab has similar costs and overall health benefits to aflibercept or ranibizumab. So, faricimab is recommended for treating diabetic macular oedema if it is used in the same population as aflibercept and ranibizumab.# Information about faricimab

# Marketing authorisation indication
Faricimab (Vabysmo, Roche) is indicated for 'the treatment of adults with visual impairment due to diabetic macular oedema'.

# Dosage in the marketing authorisation
The dosage schedule is available in the summary of product characteristics for faricimab.

# Price
Faricimab costs 857 for 1 vial of 120 mg per 1 ml solution for injection (excluding VAT; company submission, accessed April 2022).
The company has a commercial arrangement. This makes faricimab available to the NHS with a discount. The size of the discount is commercial in confidence. It is the company's responsibility to let relevant NHS organisations know details of the discount.# Committee discussion
The appraisal committee considered evidence submitted by Roche, a review of this submission by the evidence review group (ERG), and responses from stakeholders. See the committee papers for full details of the evidence.

# Comparators

## Aflibercept and ranibizumab are appropriate comparators
Aflibercept and ranibizumab are anti-vascular endothelial growth factor (anti-VEGF) injections recommended by NICE for treating diabetic macular oedema. Faricimab is another anti-VEGF injection that works in a similar way to aflibercept and ranibizumab, but it also targets the Ang2 pathway. The company proposes that faricimab will extend the time needed between injections compared with aflibercept and ranibizumab. The ERG suggested aflibercept and ranibizumab were both appropriate comparators for faricimab. Clinical experts said that the 2 treatments are both used. But they said aflibercept may be used more and it may be more effective than ranibizumab. The ERG's clinical experts suggested that 80% to 90% of people have aflibercept. The committee was aware that anti-VEGF treatments are used as a first treatment for diabetic macular oedema. It was aware that NICE's technology appraisal guidance 301 recommends fluocinolone acetonide implant if the diabetic macular oedema is insufficiently responsive to available therapies. It was also aware that NICE's technology appraisal guidance 349 recommends dexamethasone intravitreal implant if the diabetic macular oedema does not respond to non-corticosteroid treatment, or such treatment is unsuitable. The committee concluded that aflibercept and ranibizumab were the appropriate NICE-recommended comparators.

# Clinical evidence

## Evidence from 2 clinical trials, YOSEMITE and RHINE, shows similar clinical effectiveness of faricimab and aflibercept
Clinical evidence for faricimab compared with aflibercept came from 2 clinical trials. These were YOSEMITE and RHINE. Both were phase 3 randomised controlled trials that compared faricimab (using the dosing regimen in the marketing authorisation) with aflibercept in 1,259 adults. After the initial loading doses specified in the summary of product characteristics, aflibercept was given every 8 weeks and faricimab was administered as needed, with a maximum gap of 16 weeks between injections (a personalised treatment interval). The primary outcome measure was the mean change in best corrected visual acuity from baseline to 1 year. The evidence suggested that both treatments were similarly effective and had similar adverse events. The company had to break trial randomisation to provide subgroup results in people with central retinal thickness of 400 micrometres, which added uncertainty compared with results for the whole populations (these results are considered confidential by the company so cannot be presented here). Also, because there is only data up to 100 weeks, there is some uncertainty about how many faricimab injections are needed beyond the first 2 years. Despite these uncertainties, the committee considered that faricimab is likely to be similarly clinically effective as aflibercept.

## Faricimab is likely to have similar clinical effectiveness as ranibizumab
The company did a network meta-analysis comparing faricimab with ranibizumab and aflibercept. Similar to the clinical trial subgroup evidence, for the network meta-analysis the company had to break randomisation to get subgroup results for people with central retinal thickness of 400 micrometres. This made the subgroup results of the network meta-analysis uncertain (these results are academic in confidence so cannot be presented here). The ERG considered that the network meta-analysis results were potentially unreliable due to the use of inappropriate statistical methods and incorrect dosing. The committee noted that the width of the confidence intervals made it difficult to say if the treatments have similar clinical effectiveness. But clinical opinion suggests that the treatments are similarly effective. Also, the network meta-analysis results show that faricimab has comparable ocular adverse events to ranibizumab and aflibercept. The committee concluded that there was sufficient evidence of similar clinical efficacy for faricimab compared with ranibizumab.

# Cost comparison

## Faricimab is likely to be cost saving or have similar costs compared with aflibercept or ranibizumab
The company base case assumed there would be fewer injections and monitoring visits needed for faricimab compared with the comparators. But clinical experts explained that in NHS clinical practice faricimab may have a similar dosing regimen as aflibercept and ranibizumab. They explained that this is to reduce the inconsistencies in clinical practice and chance of error in busy clinical settings. Because of this, along with the lack of long-term data, the committee considered scenarios in which the number of injections and monitoring visits was the same for faricimab, aflibercept and ranibizumab after the initial loading doses. The committee acknowledged that if the time needed between injections is lengthened, then the cost of faricimab would reduce. When taking account of the commercial arrangements for all treatments, the committee was satisfied that the total cost associated with faricimab was similar or lower than aflibercept or ranibizumab (the exact results are confidential and cannot be reported here). The committee agreed that choosing the least expensive option from the available treatment options at the same point in the pathway was appropriate. The committee therefore recommended faricimab for treating diabetic macular oedema in line with the previous recommendations for aflibercept and ranibizumab.

# Other factors

## There are no equality issues relevant to the recommendations
The committee did not identify any equality issues.