Movers and SHAKERS
Can any other treatment beat anti-VEGF in macular edema?(Note: companies that could be impacted by the content of this article are listed at the base of the story (desktop version). This article uses third-party references to provide a bullish, bearish and balanced point of view; sources listed in the "Balanced" section)
Macular edema (ME) is an eye disease condition that causes the sudden or chronic decrease in visual acuity. The condition arises from fluid accumulation within the macula, an area in the center of the retina, leading to vascular instability and the breakdown of the blood-retinal barrier (BRB). Characterization of the diseases is made by the swelling and thickening of the macula distorting a person’s central vision, causing a decline in visual acuity and eventually could lead to blindness.
Major causes of macular edema include diabetes, branch and central retinal vein occlusion, choroidal neovascularization, posterior uveitis, postoperative inflammation and central serous chorioretinopathy.
Fluid accumulation results from an imbalance between processes governing fluid entry and exit, when inner or outer blood-retinal barriers are disrupted. ME can arise from various conditions:
- 7 million subjects due to diabetes, called diabetic macular edema (DME)
- 3 million subjects due to vein occlusion
- 40% of visual impairment in patients with uveitis
- 5% of individuals older than 60 years of age due to neovascular age-related macular degeneration (AMD) in industrialized countries
VEGF Therapy. The anti-vascular endothelial growth factor (VEGF) therapy has revolutionized the treatment landscape for ME and become the gold standard of care in ME following the first approval gained by Lucentis (ranibizumab) in 2010. There are currently three VEGF inhibitors (Eylea, Lucentis, and Avastin) dominating the market. Eylea has been steadily establishing itself as a market leader and reached $4 billion in sales in 2018. This is driven by the favorable clinical benefit provided by Eylea compared to Avastin and Lucentis, with the mean improvement in letter score of 18.9 ±11.5 for Eylea compared to 11.8±12.0 for Avastin and 14.2±10.6 for Lucentis. GlobalData predicts Eylea to hold 53% of the market by 2026.
VEGF inhibitors require monthly or bimonthly intravitreal injections (IVT) injections and proven to be effective in preventing further vision loss from ME, as well as improving visual acuity in many patients. Over 25% of ME patients demonstrate an inferior response to anti-VEGF treatment and require treatment with second-line corticosteroids.The current ME represent a strong and saturated market space providing a significant barrier to novel pipeline agents. Drugs looking to enter the market will have to compete against these blockbuster therapies, Eylea and Lucentis, where many has struggle to provide a clinical benefit over these efficacious therapies.
Room for improvement. The deeper understanding of the disease help identifying novel potential targets and opportunities for the development of innovative therapies. The high proportion of patients who do not respond to VEGF therapies suggests that there are potential other key modulators responsible for disease and the development of ME. Many companies are investigating novel therapeutic approaches to identify alternative aspects of the disease pathway.
Despite strong presence of VEGF inhibitors in the space, there are key factors that require improvement for standard of care of ME:
- The need for more efficacious first-line therapies: Despite the clinical benefit provided by anti-VEGF treatment, there are over 40% of patients developing resistance or fail to respond to treatment.
- Longer Duration of Action: The treatment is required every 6-7 injections per year for every anti-VEGF treatment.
- Alternative Route of Administration: The intravitreal injections (IVT) are the route of administration, which requires a health professional and clinic visit.
- Cost: Anti-VEGF treatment is a costly therapy. The average cost of therapy per eye varies for different macular edema types. Lucentis and Eylea are the more efficacious options and cost approximately $8-13.5k and $12k, respectively, exceeding the ~$400 cost of Avastin.
A key issue arises from the use of anti-VEGFs from the need for frequent invasive injections; there is a high clinical need in the market for a therapy with a longer duration of action.There are diverse approaches that are being investigated, with many companies looking to improve the current SOC by elongating activity of VEGF inhibitors, to re-formulate steroids and to identify of novel targets and pathways. The gap in the market has become the focal point of development for many companies to reduce frequency of standard of care (SOC) either in combination with these blockbuster agents or as a rival first-line therapy.
Unmet needs still exist. The ME market is a rapidly
growing and evolving landscape. Anti-VEGF therapies are expected to continue
their domination in the market despite the entry of new therapies and cheaper
biosimilars, accounting for 55% of sales in 2026 based on Global Data
estimates. Given the high clinical benefit of these therapies, the majority of
pipeline agents are looking to improve the duration of activity or to reduce
the therapy burden of anti-VEGFs. Several failures in the clinical development have
directed efforts to a combination approach and a strong unmet need still persists
in the ME landscape.
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Pennington and DeAngelis, 2016, Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors, Eye Vis., 3GlobalData, PharmaPoint: Macular Edema Global Drug Forecast and Market Analysis to 2026