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 estimated to be approved by the FDA in January 2022. The approval (or potential 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 in the wet AMD space still expected in 2021 include topline results for AR-13503 (Phase I) and GEM103 (Phase II).
- 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
24 PIPELINE DRUGS
34 KEY REGULATORY EVENTS
34 Roche’s Port Delivery System Approved, Paving The Way For Ophthalmology Expansion
34 Xbrane And Stada Celebrate Major Milestone With EU Filing For Lucentis Rival
34 Coherus Awaits August 2022 Date As FDA Accepts Ranibizumab Biosimilar
35 FDA Approves First Ophthalmic Biosimilar With Samsung Bioepis’ Lucentis Rival
35 Samsung Bioepis Scoops First EU Lucentis Biosimilar As 2022 Date Looms
35 Roche Focuses On Faricimab Durability, Mechanism In Retinal Disease
36 Roche Seeks EU Marketing Approval For Novel Eye Disease Drug Faricimab
36 Ranibizumab Implant Filed
36 Samsung Bioepis Backed By EMA For First Lucentis Biosimilar
37 Ophthalmic Bevacizumab Reaches Critical Review Stage In EU
37 Roche’s Novel Ranibizumab Implant Among Myriad New Filings In EU
37 Lupin Pursues India Approval For Lucentis Biosimilar
37 First Biosimilar Version Of Lucentis
39 PROBABILITY OF SUCCESS
40 LICENSING AND ASSET ACQUISITION DEALS
40 AbbVie Extends Reach Of Regenxbio’s Wet AMD Program
40 AbbVie Returns Worldwide Rights Of Abicipar Pegol To Molecular Partners
40 PanOptica Confirms Deal With Zhaoke For Eye Drop Rights In Asia
40 Formycon Partners With Leukocare For Stable Biosimilar Formulations
41 Janssen Licenses Gene Therapy For AMD From Hemera
41 AbCellera Teams With Kodiak To Discover Ophthalmology Antibody Candidates
41 Henlius Finds Global Partner For Ophthalmic Bevacizumab
42 AffaMed Merges With EverInsight, Marrying CBC-Launched Firms
42 OliX, Thea Expand Collaboration For Ophthalmic Diseases
43 CLINICAL TRIAL LANDSCAPE
44 Sponsors by status
45 Sponsors by phase
46 Recent events
50 DRUG ASSESSMENT MODEL
54 MARKET DYNAMICS
55 FUTURE TRENDS
55 The overall market will expand with the approvals of novel pipeline assets
55 High biologic prices will translate to high revenues, despite restricted prescribing
55 Biosimilar competition will threaten current market leaders
56 Bevacizumab’s price allows it to remain a primary option for wet AMD
57 CONSENSUS FORECASTS
59 RECENT EVENTS AND ANALYST OPINION
59 RGX-314 for Wet AMD (October 1, 2021
60 Eylea for Wet AMD (August 24, 2021)
62 Lytenava for Wet AMD (August 3, 2021)
63 Biosimilar Ranibizumab (Stada/Xbrane) for Wet AMD (June 29, 2021)
65 Beovu for Wet AMD (May 28, 2021)
66 GB-102 for Wet AMD (March 9, 2021)
67 Faricimab for Wet AMD (February 12, 2021)
69 Faricimab for Wet AMD (January 24, 2021)
70 GB-102 for Wet AMD (September 4, 2020)
72 Lytenava for Wet AMD (August 26, 2020)
74 Multiple Drugs for Wet AMD (July 27, 2020)
75 Multiple Drugs for Wet AMD (July 22, 2020)
76 Darpin for Wet AMD (June 26, 2020)
78 KEY UPCOMING EVENTS
79 UNMET NEEDS
79 Better delivery systems that allow sustained drug delivery
79 New therapies to improve long-term visual acuity
80 BIBLIOGRAPHY
82 APPENDIX
LIST OF FIGURES
19 Figure 1: Trends in prevalent cases of wet AMD, 2018–27
24 Figure 2: Overview of pipeline drugs for wet AMD in the US
24 Figure 3: Pipeline drugs for wet AMD, by company
25 Figure 4: Pipeline drugs for wet AMD, by drug type
25 Figure 5: Pipeline drugs for wet AMD, by classification
39 Figure 6: Probability of success in the wet AMD pipeline
43 Figure 7: Clinical trials in wet AMD
43 Figure 8: Top 10 drugs for clinical trials in wet AMD
44 Figure 9: Top 10 companies for clinical trials in wet AMD
44 Figure 10: Trial locations in wet AMD
45 Figure 11: Wet AMD trials status
46 Figure 12: Wet AMD trials sponsors, by phase
50 Figure 13: Datamonitor Healthcare’s drug assessment summary for wet AMD
54 Figure 14: Market dynamics in wet AMD
55 Figure 15: Future trends in wet AMD
60 Figure 16: RGX-314 for Wet AMD (October 1, 2021): Phase II – AAVIATE
62 Figure 17: Eylea for Wet AMD (August 24, 2021): Phase II – CANDELA
63 Figure 18: Lytenava for Wet AMD (August 3, 2021): Phase III – NORSE 2
65 Figure 19: Biosimilar Ranibizumab (Stada/Xbrane) for Wet AMD (June 29, 2021): Phase III – XPLORE
67 Figure 20: GB-102 for Wet AMD (March 9, 2021): Phase IIb – ALTISSIMO
69 Figure 21: Faricimab for Wet AMD (February 12, 2021): Phase III – LUCERNE, Phase III – TENAYA
70 Figure 22: Faricimab for Wet AMD (January 24, 2021): Phase III – LUCERNE, Phase III – TENAYA
72 Figure 23: GB-102 for Wet AMD (September 4, 2020): Phase I/IIa – ADAGIO
74 Figure 24: Lytenava for Wet AMD (August 26, 2020): Phase III – NORSE 1 (Australia)
76 Figure 25: Multiple Drugs for Wet AMD (July 22, 2020): Phase III – Archway
78 Figure 26: 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
26 Table 5: Pipeline drugs for wet AMD
57 Table 6: Historical global sales, by drug ($m), 2016–20
58 Table 7: Forecasted global sales, by drug ($m), 2021–25
59 Table 8: RGX-314 for Wet AMD (October 1, 2021)
61 Table 9: Eylea for Wet AMD (August 24, 2021)
62 Table 10: Lytenava for Wet AMD (August 3, 2021)
64 Table 11: Biosimilar Ranibizumab (Stada/Xbrane) for Wet AMD (June 29, 2021)
65 Table 12: Beovu for Wet AMD (May 28, 2021)
66 Table 13: GB-102 for Wet AMD (March 9, 2021)
68 Table 14: Faricimab for Wet AMD (February 12, 2021)
69 Table 15: Faricimab for Wet AMD (January 24, 2021)
71 Table 16: GB-102 for Wet AMD (September 4, 2020)
72 Table 17: Lytenava for Wet AMD (August 26, 2020)
74 Table 18: Multiple Drugs for Wet AMD (July 27, 2020)
75 Table 19: Multiple Drugs for Wet AMD (July 22, 2020)
76 Table 20: Darpin for Wet AMD (June 26, 2020)
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