Will switching to Vabysmo from Eylea lead to less frequent injections in neovascular AMD?

A 63 year old European man came to see me in Retina Specialists. He was worried about his neovascular age-related macular degeneration (nAMD). He has been receiving regular injections in Greenlane Clinical Centre every four weeks for neovascular (wet) changes. Although his right eye sees ok (6/9), his left eye is poorly with an acuity of 6/30 and he would experience a recurrence of the subretinal fluid if the injections are more than four weeks apart. He initially had Avastin (Bevacizumab) injections, which was ineffective, and then Eylea (Aflibercept) which he developed an inflammatory response, and currently the treatment is with Lucentis (Ranibizumab). He wants to know that whether Vabysmo (Faricimab) treatment will decrease his reliance of these injections, leading to better control, and ultimately increase the treatment interval.

However, complicating the clinical scenario is that this patient has no medical insurance. So he will be self-funding for both the Vabysmo medication and the treatment cost in private, as the medication is not available in the public system. He will need to continue working, defer retirement and potentially sell down some of his asset in the longer term, as the financial burden of Vabysmo is considerable for him.

If you were his doctor, how would you advise him?

Vabysmo - a Promise of Better Fluid Control and Less Treatments?

Vabysmo (Faricimab) is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. In the pivotal phase-3 trials Teneya and and Lucerne, the efficiency of Vabysmo is compared to Eylea in patients with treatment naive nAMD. The trial design is summarised in the diagram below.

In the Vabysmo group, all patients received a course of four injections four weeks apart as loading, and then move to Q8w, Q12w, or Q16w depending on if there is neovascular activity present in week 20 and 24. However, in the Eylea group, all patients received fixed Q8w injections after a course of three injections four weeks apart.

However, we know that many patients can extend their treatment interval to >Q8w with Eylea using the treat-and-extend protocol. So although it is true that "Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD." (study conclusion of Teneya and Lucerne), it is also likely that a proportion of patients in the Eylea group can extend beyond Q8w.

Indeed, there is no difference in visual acuity outcomes between Vabysmo and Eylea.

And, fluid appears to be better controlled under Vabysmo (notice the saw-tooth pattern on the mean CST change in the Eylea group, which suggest suboptimal fluid control).

The RIVAL Study - a Cautionary Tale

I have been practising ophthalmology for a while, and I remember how Eylea was marketed as a drug that lasted longer than Lucentis (Q8wk vs Q4wk). There was a lot of excitement about the longer durability, and I believe that part of the PHARMAC decision to fund Eylea was based of the projection that patients may require less frequent injections.

However, our colleagues in Australia very cleverly ran a study (the RIVAL study) comparing Lucentis and Eylea, but under the treat-and-extend protocol. Surprisingly, there is no difference in the number of injections given during the study period between the two drug, suggesting that Eylea does not lead to a longer treatment interval compared to Lucentis.

There is no difference in visual acuity outcome between Lucentis and Eylea.

Evidence from Studies Looking at Existing nAMD Patients Switching to Vabysmo

There are not many studies looking at the effect of existing nAMD patients with suboptimal response to other anti-VEGF switching to Vabysmo (Khanani 2023, Leung 2023, Raimondi 2024 - retrospective chart review, Rush 2022 - retrospective cohort study). All of these studies are small and non-randomised, with a short follow up time.

Looking at the visual acuity data, after a switch to Vabysmo, there is a heterogeneous response in terms of acuity improvement. However, the composite effect (black line) is similar to the control data, suggesting that even if there is visual acuity gain, the effect is likely small.

However, the data on the improvement in central macular thickness is more convincing, with studies reporting at least a 20um improvement to more than 60um improvement.

Leung 2023 reported on the treatment interval data, showing that a switch to Vabysmo in this cohort resulted in a modest lengthening of the treatment interval to 7.5 weeks, and 23% of patients on Vabysmo achieve a completely dry macula.

What is my recommendation?

The data suggests that a switch to Vabysmo from Eylea for nAMD is likely going to be beneficial, in terms of fluid control. However, the gain in treatment interval is likely to be more modest than what is suggested in TENEYA and LUCERNE. So, for a patient who is insufficiently controlled with Eylea at Q4w, it will be unlikely for this patient to be able to have a completely dry macula at Q16w with Vabysmo. As Leung 2023 suggests, the gain in treatment interval may only be a few weeks.

For most of these patients wanting to switch to Vabysmo, but are stable on frequent Eylea injections, it is reasonable to stay on Eylea until Vabysmo is funded by PHARMAC. This is especially so for those patients who do not have medical insurance and will be self-funding both the treatment cost and the drug cost out of pocket. For those with medical insurance and not under financial strain, a limited trial of three to six Vabysmo injections will be useful to see if one can achieve better control with this medication.

The cost of Vabysmo is around $1800, but at the present time, Roche is running a cost-share scheme and the medication can be offered as a more accessible price.

About Dr Leo Sheck

Dr Sheck is a RANZCO-qualified, internationally trained ophthalmologist. He combined his initial training in New Zealand with a two-year advanced fellowship in Moorfield Eye Hospital, London. He also holds a Doctorate in Ocular Genetics from the University of Auckland and a Master of Business Administration from the University of Cambridge. He specialises in medical retina diseases (injection therapy), cataract surgery, ocular genetics, uveitis and electrodiagnostics.