What Will the Next Decade Have in Store?
Monoclonal antibodies against vascular endothelial growth factor (VEGF) revolutionized the treatment of wet age-related macular degeneration when they first arrived on the market over a decade ago. These agents inhibit neovascularization of the retina, preventing tissue destruction as well as the debilitating vision loss associated with leaky, abnormal blood vessel development. For the past several years, Novartis/Roche/Genentech’s Lucentis and Regeneron/Bayer/Santen’s Eylea have dominated the competitive landscape for wet AMD in the seven major pharmaceutical markets, along with a third major player, Roche’s Avastin, which is routinely compounded for intravitreal (IVT) injection in the United States, providing a less-expensive, off-label option. These three anti-VEGF therapies are effective and safe and have therefore set the bar high for new market entrants.
However, anti-VEGF therapies have three major limitations which leave room for improvement and ample commercial opportunity in this >$4 billion and-growing market. First, to remain effective and prevent disease worsening, Lucentis, Eylea, and Avastin require regular monthly IVT injections over the course of patients’ lifetimes, creating an enormous treatment burden for physicians, patients, and ophthalmology clinics. Secondly, as biologic therapies, these products are expensive, putting tremendous pressure on health care systems and third-party insurers (e.g., Lucentis and Eylea both approach $2,000 per dose in the United States). Finally, anti-VEGF therapies are ineffective for geographic atrophy (sometimes referred to as dry AMD), a type of late age-related macular degeneration where large areas of photoreceptors are permanently lost on the retina, leading to the deterioration of central vision. Over the next decade, we expect several new products to launch that will address these unmet needs—leading to increased market fragmentation and entirely different market dynamics from those existing today.
Next generation anti-VEGF therapies promise increased dosing intervals and reduced injection burden. Over the next five years, we forecast two anti-VEGF products will launch that could potentially offer dosing once every 12 weeks: Novartis’s RTH-258 (brolucizumab) and Allergan’s abicipar pegol. Eylea’s patient share for wet AMD has benefited substantially from its slightly longer dosing interval than Lucentis, as many patients can be maintained on once every 8-week dosing. Therefore, we expect this value proposition to continue to motivate prescribing decisions, and to drive the uptake of both RTH-258 and abicipar pegol.
Biosimilars will increase pricing pressure on wet AMD therapies. Biosimilar versions of Lucentis are expected to start entering the market in 2020 and will put increased pricing pressure on branded therapies for wet AMD--especially because the high cost of approved wet AMD therapies combined with the relatively large size of the target population places a heavy burden on healthcare systems. Furthermore, branded anti-VEGF therapies may be particularly vulnerable to proposed changes in the Medicare payment formula by the Centers for Medicare & Medicaid Services in the United States that would if passed, decrease what is paid for injected therapies. Not only are biosimilar versions of Lucentis (and later, Eylea) expected to impact the corresponding brand, but they will affect the uptake of next-generation anti-VEGF therapies as well.
Complement factor inhibitors may provide a long-awaited pharmacological option for the treatment of GA. We expect one therapy for GA to launch during the forecast period—Roche/Genentech’s complement factor D-inhibiting monoclonal antibody lampalizumab. As the first therapy approved for this indication in the United States and Europe, we forecast this drug will rapidly create a new drug-treated patient population and reach blockbuster status by 2023. Earlier in development is Ophthotech’s Zimura, a monoclonal antibody against complement factor C5 that may also eventually compete in this market segment, should Ophthotech advance the drug into pivotal Phase III studies.
With the increased fragmentation and expansion of the AMD market that is expected over the next five years, several key business questions emerge regarding how new AMD therapies will be adopted by physicians, used by patients, and reimbursed by insurers. In-depth analysis of the current and future competitive landscape can be found in DRG’s 2017 Age-Related Macular Degeneration Disease Landscape and Forecast report published this month, which includes an annualized 2016-2026 market forecast and anti-VEGF biosimilars assumptions.