Age-related macular degeneration (AMD) is the progressive degradation of the part of the eye responsible for visual acuity, causing a loss of central vision. AMD is the leading cause of blindness in individuals who are over 65 years old. As the chances of experiencing any form of AMD increase with age, treatment of this disease is becoming even more important as life expectancies continue to rise in most regions.
LATEST KEY TAKEAWAYS
- Due to their ability to improve clinical outcomes and treat a more comprehensive patient population, vascular endothelial growth factor (VEGF) inhibitors have become the standard treatment used in wet age-related macular degeneration (wet AMD).
- Currently, the use of photodynamic therapy with Visudyne, both alone and in combination with other treatments, is principally restricted to the second line of therapy and/or patients with the retinal angiomatous proliferation (RAP) or polypoidal choroidal vasculopathy (PCV) subtypes of AMD.
- Even with Roche’s efforts to position Lucentis ahead of Avastin, and the introduction of Eylea into the market, bevacizumab’s low price continues to merit its off-label use in wet AMD. Although the treatment of cancer with bevacizumab can be costly, a much smaller dose of 1.25mg is used in wet AMD, dropping the cost of the drug to approximately $50 per dose. By comparison, a single dose of Lucentis costs approximately $1,950.
- Despite the availability of cheap off-label bevacizumab and payer pressure to utilize bevacizumab prior to branded drugs, biologic therapies Eylea and Lucentis produce substantial revenues year-on-year due to their high prices and given the chronic nature of the disease and recurring treatment schedules. In 2020, Regeneron and partners earnt $8bn in total sales from Eylea, making it the sixth highest earning drug of the year overall.
- Eylea and Lucentis will face biosimilar competition within the next few years given that the US Lucentis patent expired in June 2020. Although Eylea’s US patent is not set to expire until 2023, the drug will likely face indirect competition prior to this date from ranibizumab biosimilars. In September 2021, Biogen’s Byooviz became the first ranibizumab biosimilar to gain US approval, but the company does not plan to commercialize its product before June 2022. Pipeline ranibizumab biosimilars include STADA Arzneimittel’s Xlucane and Coherus’s CHS-201.
- Novartis’s Beovu (brolucizumab-dbll) was approved by the FDA in October 2019 based on two Phase III trials (HAWK and HARRIER) demonstrating non-inferiority to Eylea. However, post-marketing safety issues have marred the uptake of this drug and will thwart Novartis’s hopes of taking substantial market share from Eylea.
- In an effort to curtail sales erosion from ranibizumab biosimilars, Roche has developed two assets: ranibizumab Port Delivery System (Susvimo), and faricimab, which feature long periods of time between recurring treatments. Susvimo, an eye implant that contains six months worth of ranibizumab, was approved by the FDA in October 2021 and is the most recent addition to the wet AMD market. It should become an established product in the marketplace before the release of cheaper biosimilar ranibizumab. Faricimab, a bispecific antibody, is expected to be approved by the FDA in January 2022. The approval and subsequent uptake of these assets will contribute directly to the forecasted growth of the wet AMD market.
- An increase in disease prevalence will also contribute to market growth. Datamonitor Healthcare estimates that in 2018, there were approximately 14.5 million prevalent cases of wet AMD in adults aged 50 years and over worldwide, and forecasts that number to increase to 17.6 million prevalent cases by 2027.
- High-impact upcoming events for drugs in the wet AMD space include topline results for KSI-301 and GEM103. In addition, the FDA will be reviewing faricimab’s BLA by the end of January 2022.
- Recent topline results include Phase II data from AbbVie’s anti-VEGF gene therapy, RGX-314, which demonstrated stable visual acuity and central retinal thickness as well as a decrease in injection burden compared to the active comparator arm (Lucentis). Additionally, Outlook Therapeutics released highly positive Phase III data for Lytenava, a bevacizumab formulation specifically for ophthalmic use, which showed clinical superiority over Lucentis.
- Despite the availability of anti-VEGF medicines that have revolutionized the treatment of wet AMD, pressing unmet needs remain. The challenge of recurring monthly or two-monthly injections over the span of years is difficult for patients, and studies analyzing real-world claims data indicate adherence to treatment is low and patients are generally undertreated, receiving fewer injections and less monitoring than in clinical trials. There is therefore a great need for better treatments that improve visual acuity, allow sustained delivery, are long-acting, and lower patient treatment burdens.