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.
CONTENTS
7 OVERVIEW
9 DISEASE BACKGROUND
9 Definition
9 Patient subtypes
10 Subtypes
11 Symptoms
12 Risk factors
12 Diagnosis
13 TREATMENT
16 VEGF inhibitors form the current standard treatment
16 Photodynamic therapy is typically reserved for specific subpopulations
16 Laterality
17 EPIDEMIOLOGY
17 Prevalence methodology
20 MARKETED DRUGS
23 PIPELINE DRUGS
31 KEY REGULATORY EVENTS
31 EMA Rejects Bevacizumab Drug For Use In Wet AMD
31 Roche’s Port Delivery System Approved, Paving The Way For Ophthalmology Expansion
32 Xbrane And Stada Celebrate Major Milestone With EU Filing For Lucentis Rival
32 Coherus Awaits August 2022 Date As FDA Accepts Ranibizumab Biosimilar
32 FDA Approves First Ophthalmic Biosimilar With Samsung Bioepis’ Lucentis Rival
33 Samsung Bioepis Scoops First EU Lucentis Biosimilar As 2022 Date Looms
33 Roche Focuses On Faricimab Durability, Mechanism In Retinal Disease
33 Roche Seeks EU Marketing Approval For Novel Eye Disease Drug Faricimab
34 Ranibizumab Implant Filed
34 Samsung Bioepis Backed By EMA For First Lucentis Biosimilar
34 Ophthalmic Bevacizumab Reaches Critical Review Stage In EU
35 Roche’s Novel Ranibizumab Implant Among Myriad New Filings In EU
35 Lupin Pursues India Approval For Lucentis Biosimilar
36 PROBABILITY OF SUCCESS
37 LICENSING AND ASSET ACQUISITION DEALS
37 CURACLE, Théa To Develop Diabetic Macular Edema, Wet AMD Therapeutic
37 AbbVie Extends Reach Of Regenxbio’s Wet AMD Program
37 AbbVie Returns Worldwide Rights Of Abicipar Pegol To Molecular Partners
37 PanOptica Confirms Deal With Zhaoke For Eye Drop Rights In Asia
38 Formycon Partners With Leukocare For Stable Biosimilar Formulations
39 CLINICAL TRIAL LANDSCAPE
40 Sponsors by status
41 Sponsors by phase
42 Recent events
46 DRUG ASSESSMENT MODEL
50 MARKET DYNAMICS
51 FUTURE TRENDS
51 The overall market will expand with the approvals of novel pipeline assets
51 High biologic prices will translate to high revenues, despite restricted prescribing
51 Biosimilar competition will threaten current market leaders
52 Bevacizumab’s price allows it to remain a primary option for wet AMD
53 CONSENSUS FORECASTS
55 RECENT EVENTS AND ANALYST OPINION
55 RBM-007 for Wet AMD (December 28, 2021)
56 RGX-314 for Wet AMD (October 1, 2021)
58 Eylea for Wet AMD (August 24, 2021)
60 Lytenava for Wet AMD (August 3, 2021)
61 Biosimilar Ranibizumab (Stada/Xbrane) for Wet AMD (June 29, 2021)
63 Beovu for Wet AMD (May 28, 2021)64 GB-102 for Wet AMD (March 9, 2021)
65 Faricimab for Wet AMD (February 12, 2021)
67 Faricimab for Wet AMD (January 24, 2021)
68 GB-102 for Wet AMD (September 4, 2020)
70 Lytenava for Wet AMD (August 26, 2020)
72 Multiple Drugs for Wet AMD (July 27, 2020)
73 Multiple Drugs for Wet AMD (July 22, 2020)
75 KEY UPCOMING EVENTS
76 UNMET NEEDS
76 Better delivery systems that allow sustained drug delivery
76 New therapies to improve long-term visual acuity
77 BIBLIOGRAPHY
79 APPENDIX
LIST OF FIGURES
19 Figure 1: Trends in prevalent cases of wet AMD, 2018–27
23 Figure 2: Overview of pipeline drugs for wet AMD in the US
23 Figure 3: Pipeline drugs for wet AMD, by company
24 Figure 4: Pipeline drugs for wet AMD, by drug type
24 Figure 5: Pipeline drugs for wet AMD, by classification
36 Figure 6: Probability of success in the wet AMD pipeline
39 Figure 7: Clinical trials in wet AMD
39 Figure 8: Top 10 drugs for clinical trials in wet AMD
40 Figure 9: Top 10 companies for clinical trials in wet AMD
40 Figure 10: Trial locations in wet AMD
41 Figure 11: Wet AMD trials status
42 Figure 12: Wet AMD trials sponsors, by phase
46 Figure 13: Datamonitor Healthcare’s drug assessment summary for wet AMD
50 Figure 14: Market dynamics in wet AMD
51 Figure 15: Future trends in wet AMD
56 Figure 16: RBM-007 for Wet AMD (December 28, 2021): Phase II – TOFU
58 Figure 17: RGX-314 for Wet AMD (October 1, 2021): Phase II – AAVIATE
60 Figure 18: Eylea for Wet AMD (August 24, 2021): Phase II – CANDELA
61 Figure 19: Lytenava for Wet AMD (August 3, 2021): Phase III – NORSE 2
63 Figure 20: Biosimilar Ranibizumab (Stada/Xbrane) for Wet AMD (June 29, 2021): Phase III – XPLORE
65 Figure 21: GB-102 for Wet AMD (March 9, 2021): Phase IIb – ALTISSIMO
67 Figure 22: Faricimab for Wet AMD (February 12, 2021): Phase III – LUCERNE, Phase III – TENAYA
68 Figure 23: Faricimab for Wet AMD (January 24, 2021): Phase III – LUCERNE, Phase III – TENAYA
70 Figure 24: GB-102 for Wet AMD (September 4, 2020): Phase I/IIa – ADAGIO
72 Figure 25: Lytenava for Wet AMD (August 26, 2020): Phase III – NORSE 1 (Australia)
74 Figure 26: Multiple Drugs for Wet AMD (July 22, 2020): Phase III – Archway
75 Figure 27: Key upcoming events in wet AMD
LIST OF TABLES
11 Table 1: Segmentation of neovascular lesions, by angiographic presentation
14 Table 2: Treatment guidelines overview
18 Table 3: Prevalent cases of wet AMD, 2018–27
21 Table 4: Marketed drugs for wet AMD
25 Table 5: Pipeline drugs for wet AMD
53 Table 6: Historical global sales, by drug ($m), 2016–20
54 Table 7: Forecasted global sales, by drug ($m), 2022–26
55 Table 8: RBM-007 for Wet AMD (December 28, 2021)
57 Table 9: RGX-314 for Wet AMD (October 1, 2021)
59 Table 10: Eylea for Wet AMD (August 24, 2021)
60 Table 11: Lytenava for Wet AMD (August 3, 2021)
62 Table 12: Biosimilar Ranibizumab (Stada/Xbrane) for Wet AMD (June 29, 2021)
63 Table 13: Beovu for Wet AMD (May 28, 2021)
64 Table 14: GB-102 for Wet AMD (March 9, 2021)
66 Table 15: Faricimab for Wet AMD (February 12, 2021)
67 Table 16: Faricimab for Wet AMD (January 24, 2021)
69 Table 17: GB-102 for Wet AMD (September 4, 2020)
70 Table 18: Lytenava for Wet AMD (August 26, 2020)
72 Table 19: Multiple Drugs for Wet AMD (July 27, 2020)
73 Table 20: Multiple Drugs for Wet AMD (July 22, 2020)
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