Clearer vision for wet AMD sufferers in sight

A new treatment option is now available for the management of wet age-related macular degeneration (AMD). Brolucizumab, the first single-chain antibody fragment (scFv) designed specifically for intraocular use in humans.

Wet AMD is a chronic disease in which abnormal blood vessels form beneath the macula. The macula is the core region of the retina that is responsible for central vision that is sharp and clear, as well as colour perception.

“These blood vessels are fragile and can leak, causing fluid and even blood to build up in the macula, hence the term ‘wet’ AMD. The leaking disrupts the normal macula architecture which ultimately damages and scars the macula, causing patients to experience a deterioration in their vision,” said Dr Nor Fariza Ngah, national head of Ophthalmology Services, Ministry of Health Malaysia.

In the early stages, wet AMD causes distorted vision (metamorphopsia) and difficulty seeing objects clearly. It is critical to diagnose and intervene as soon as possible. As the condition continues, cell damage worsens, lowering vision quality and may lead to a full loss of central vision, preventing people from reading, driving, or recognizing faces. This can eventually lead to loss of independence.

Anti-VEGF therapy inhibits the formation of abnormal blood vessels and subsequent leakage into the retina. Brolucizumab was engineered to deliver a high concentration of drug to the target area, higher than other anti-VEGF molecules. [Ophthalmology 2020;127:72–84]

Brolucizumab’s approval comes in the wake of the phase III HAWK* and HARRIER** trials, in which brolucizumab demonstrated non-inferiority versus aflibercept in mean change in best-corrected visual acuity (BCVA) at week 48. The HAWK and HARRIER trials are global head-to-head trials in patients with wet AMD. They recruited over 1,800 patients across almost 400 facilities worldwide. The studies used a unique q12w/q8w dosing regimen where the initial treatment after the loading phase was one injection every 12 weeks (q12w). If disease activity was identified at any of the assessments, dosing was adjusted to one injection every 8 weeks (q8w). Once participants were adjusted to q8w, they stayed on that interval until the end of the study.

The dosing regimen showed efficacy at week 48, with the majority of patients staying on q12w immediately after the loading phase. Both studies are part of brolucizumab’s phase III clinical development and are 96-week prospective, randomized, double-masked multicentre investigations. The studies compared the efficacy and safety of brolucizumab 6 mg (HAWK and HARRIER) and 3 mg (HAWK alone) intravitreal injections vs aflibercept 2 mg in patients with wet AMD. [Ophthalmology 2020;127:72–84]

“Brolucizumab meets our goals in clinical practice for treating wet AMD: improving vision and drying retinal fluid,” said Patrik Grande, president and managing director, Novartis Malaysia. Compared with existing anti-VEGF treatments, Grande said the potential of 3-monthly dosing intervals with brolucizumab may allow for less frequent injections. This can alleviate a burden for patients and their caregivers, improving compliance and overall outcomes.

About wet AMD

Approximately 200 million people worldwide are affected by wet AMD, which is the leading cause of severe vision loss and blindness in people over the age of 65 in North America, Europe, Australia, and Asia. [Lancet Glob Health 2014;2:e106–116] An estimated 46,000 Malaysians over the age of 45 are known to suffer from the eye disorder, which puts them at risk of developing irreversible blindness if the condition is not treated. [https://www.nst.com.my/lifestyle/heal/2020/06/603622/elderly-face-risk-irreversible-blindness]

*HAWK: Efficacy and Safety of RTH258 Versus Aflibercept - Study 1

**HARRIER: Efficacy and Safety of RTH258 Versus Aflibercept - Study 2

Ed: An analysis of adverse events after brolucizumab injection identified a number of cases with signs of retinal vasculitis with or without signs of retinal vascular occlusion, and such events were associated with increased risk of visual acuity loss. It is critical that treating physicians monitor appropriately for this during brolucizumab treatment. [Available at https://www.aaojournal.org/article/S0161-6420(20)31075-7/fulltext Accessed on 9 September 2021]