Faricimab for neovascular age-related macular degeneration and diabetic macular oedema

Approved indications: neovascular (wet) age-related macular degeneration, diabetic macular oedema
Vabysmo (Roche)
vials containing 28.8 mg faricimab in 0.24 mL solution for intravitreal injection

Faricimab is the first bispecific monoclonal antibody for intraocular use, approved for treatment of neovascular (wet) age-related macular degeneration and diabetic macular oedema. Neovascular age-related macular degeneration (nAMD) is a form of advanced AMD characterised by abnormal proliferation of new blood vessels beneath the retina and macula (choroidal neovascularisation). These blood vessels leak fluid, lipids and blood into the outer retina, causing severe, irreversible loss of central vision if untreated. Approximately 21,000 new cases of nAMD are diagnosed in Australia each year.¹ Diabetic macular oedema is a complication of diabetic retinopathy associated with fluid leakage from damaged blood vessels and swelling of the macula, resulting in loss of central vision.

Faricimab inhibits pathological angiogenesis and restores vascular stability in the eye. It acts by binding to vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2), reducing vascular permeability and inflammation via 2 distinct pathways. Other VEGF inhibitors available in Australia are aflibercept, brolucizumab and ranibizumab. These drugs have substantially improved visual outcomes in patients with nAMD and diabetic macular oedema; however, long-term treatment is required, with frequent clinic visits for monitoring and intraocular injections.

The efficacy of faricimab versus aflibercept for nAMD was assessed in 2 identical randomised, double-blind phase 3 noninferiority trials: TENAYA and LUCERNE (pooled n=1329 participants aged 50 years or older). Participants were randomised to receive intravitreal faricimab 6 mg up to every 16 weeks (interval modified according to disease activity), or aflibercept 2 mg every 8 weeks. The primary endpoint was mean change in best corrected visual acuity (BCVA) at week 48, measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) tool.* Faricimab was found to be noninferior to aflibercept in these trials, with participants in both the faricimab and aflibercept groups gaining approximately 6 ETDRS letters in reading improvement in both trials. At week 48, approximately 80% of faricimab-treated patients were on 12-week or 16-week dosing intervals.² Study treatment was administered up to week 108, but longer-term outcomes have not yet been reported.

The efficacy of faricimab for diabetic macular oedema was also assessed in 2 identical randomised, double-blind phase 3 noninferiority trials: YOSEMITE and RHINE (pooled n=1891 participants with an average age of 62 years). Participants were randomised to receive intravitreal faricimab 6 mg every 8 weeks, faricimab 6 mg per personalised treatment interval (ranging from every 4 weeks up to every 16 weeks, modified according to disease activity), or aflibercept 2 mg every 8 weeks. The primary endpoint was mean change in BCVA at week 52. Faricimab was found to be noninferior to aflibercept in both trials, with participants who received faricimab every 8 weeks or at a variable dosage interval, or aflibercept, gaining approximately 11 ETDRS letters in reading improvement. At week 52, more than 70% of patients who received faricimab at variable intervals were on 12-week or 16-week dosing intervals.³ Improvements in visual acuity were maintained at 2 years.⁴

Safety of faricimab was assessed in 1926 patients across the 4 above-mentioned phase 3 trials for nAMD and diabetic macular oedema. Rates of ocular adverse events were similar for faricimab and aflibercept, ranging from 31 to 47% in different arms of the studies. Most of these events were mild or moderate in severity. In the pooled data for faricimab, the most frequently reported ocular adverse effects were cataract (10.7%), conjunctival haemorrhage (7.3%), increased intraocular pressure (3.6%), vitreous floaters (3.6%), eye pain (2.5%) and retinal pigment epithelial tear (nAMD only) (2.9%). Serious adverse effects included cataract (0.9%), uveitis (0.5%), endophthalmitis (0.3%), vitritis (0.3%), retinal tear (0.2%) and rhegmatogenous retinal detachment (less than 0.1%).⁵ Common non-ocular adverse events were generally similar for faricimab and aflibercept.⁵

Rare cases of retinal vasculitis and/or retinal occlusive vasculitis have been reported in patients treated with faricimab in the postmarketing setting. This is discussed in a recent Medicines Safety Update published by the Therapeutic Goods Administration.

The recommended dosage of faricimab for both nAMD and diabetic macular oedema is 6 mg by intravitreal injection every 4 weeks for the first 4 doses, followed by individualised dosing based on anatomic or visual outcomes (every 8 to 16 weeks for nAMD, and every 4 weeks but may be extended in 4-week increments up to every 16 weeks for diabetic macular oedema). Continued monitoring of disease activity and individualisation of dosing is recommended.⁵

In conclusion, faricimab provides clinical benefits for patients with nAMD and diabetic macular oedema, and has the potential to extend treatment intervals, thus reducing visits and treatment burden for the patient.

* Early Treatment Diabetic Retinopathy Study tool for visual acuity, calculated as number of letters read correctly on a chart displaying 70 letters, from a specified distance, plus 30; maximum score 100.

🅃 🅃  manufacturer provided additional useful information. The Transparency Score is explained in New drugs: transparency, Vol 37 No 1, Aust Prescr 2014;37:27.

At the time the comment was prepared, information about this drug was available on the websites of the Food and Drug Administration in the USA, the European Medicines Agency and the Therapeutic Goods Administration.

 

References

1. Macular Disease Foundation Australia. [cited 2024 Jan 30]
2. Heier JS, Khanani AM, Quezada Ruiz C, Basu K, Ferrone PJ, Brittain C, et al. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials. Lancet 2022;399:729-40.
3. Wykoff CC, Abreu F, Adamis AP, Basu K, Eichenbaum DA, Haskova Z, et al. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials. Lancet 2022;399:741-55.
4. Wong TY, Haskova Z, Asik K, Baumal CR, Csaky KG, Eter N, et al. Faricimab Treat-and-Extend for Diabetic Macular Edema: 2-Year Results from the Randomized Phase 3 YOSEMITE and RHINE Trials. Ophthalmology 2023.
5. Therapeutic Goods Administration. Australian Product Information – Vabysmo (faricimab) solution for intravitreal injection VA2.0. Canberra: Department of Health and Aged Care; 2023. [cited 2024 Feb 6]

 The new drug commentaries in Australian Prescriber are prepared by the Editorial Advisory Committee. Some of the views expressed on newly approved products should be regarded as preliminary, as there may be limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Advisory Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.