Disease Analysis: Alzheimer’s Disease
Publisher: Datamonitor Healthcare
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Disease Overview
Alzheimer’s disease is an irreversible, progressive, neurodegenerative disease that slowly affects memory, cognition, and function. It is a continuum of pathological changes in the brain that begin well before clinical symptoms emerge. The hallmark abnormalities of Alzheimer’s disease are beta-amyloid deposits and tau tangles in the brain, while it is also characterized by the loss of neuronal connections. These pathological changes are thought to occur years in advance of the onset of dementia in patients with Alzheimer’s disease. Studies indicate that people aged 65 years and over survive an average of four to eight years after a diagnosis of Alzheimer’s disease, yet some live as long as 20 years or more, indicating the slow, insidious progression of the disease.
Latest key takeaways
- Datamonitor Healthcare estimates that in 2021, there were 82.8 million prevalent cases of Alzheimer’s disease in adults aged 65 years and older worldwide, and forecasts that number to increase to 102.5 million prevalent cases by 2027.
- Symptomatic treatments largely consist of four well-established products. The acetylcholinesterase class of drugs will continue to dominate the treatment of mild Alzheimer’s disease, while NMDA receptor antagonist memantine is used primarily as an add-on or second-line therapy in more severe disease stages.
- The landmark, yet controversial, accelerated approval of Biogen and Eisai’s anti-amyloid antibody Aduhelm came despite Phase III clinical trial data resulting in one positive and one negative study. In its release of this groundbreaking news, the US FDA acknowledged there is some uncertainty around the data, but reiterated that the treatment is the first to show a benefit in amyloid plaque reduction, thus targeting the underlying disease pathology rather than masking symptoms. The EU has declined to follow the FDA in approving Aduhelm, while Japanese authorities have requested more data.
- The FDA’s accelerated approval of Aduhelm based on amyloid reduction rather than cognitive improvement lowered the bar for approval, though market access barriers remain. Medicare will cover about 80% of the cost of anti-amyloid antibodies, and CMS will only cover drugs using the accelerated approval pathway under an FDA-approved randomized controlled trial that evaluates clinical benefit, severely limiting patient access.
- Topline results from Phase III trials of Roche’s gantenerumab (GRADUATE 1 and 2) and Eisai’s lecanemab (Clarity AD) are expected before the end of 2022. Eli Lilly’s TRAILBLAZER-ALZ 2 trial of donanemab is expected to read out in mid-2023.
- Donanemab may be able to clear amyloid plaques from the brain at the fastest rate among its competitors, thus enabling a limited treatment duration. Lecanemab has the lowest rates of amyloid-related imaging abnormalities (ARIA), thus eliminating the need for a dose titration period. Gantenerumab has favorable monthly subcutaneous dosing, though subcutaneous formulations of competitors are being evaluated.
- Despite current uncertainties around efficacy and barriers to access, a high unmet need may ultimately create a lucrative market for anti-amyloid antibodies.
CONTENTS
7 OVERVIEW
7 Latest key takeaways
8 DISEASE BACKGROUND
8 Definition
8 Symptoms
8 Risk factors
8 Patient segmentation
11 TREATMENT
11 Cholinesterase inhibitors are recommended for mild-to-moderate Alzheimer’s disease
11 Memantine is reserved for moderate-to-severe disease
11 Aduhelm becomes the first anti-amyloid antibody approved for early Alzheimer’s disease
12 EPIDEMIOLOGY
16 MARKETED DRUGS
20 PIPELINE DRUGS
35 KEY REGULATORY EVENTS
35 Future Of Acadia’s Nuplazid In Alzheimer’s Psychosis Unclear After CRL
35 Eisai/Biogen Maintain Lead Over Lilly In New Race To Alzheimer’s Approval
35 Acadia’s Nuplazid Needs Another Study For Alzheimer’s Psychosis, US FDA Panel Says
36 Eisai’s Lecanemab BLA Filing A Key Step For Ailing Biogen
36 Aduhelm Label Update Includes Seizure Risk And Recommends More MRIs
37 Biogen Pulls EU Filing For Aduhelm But Stands By Alzheimer’s Drug
37 Medicare Alzheimer’s Decision Varies Evidence Mandate For Accelerated vs. Traditional Approvals
38 Corium’s Corplex Joins Rx Market With Adlarity Approval
38 AbbVie Continues Development Of Novel Synaptic Function Modulators
38 Medicare Coverage-In-Clinical-Trials Policy For Alzheimer’s Drugs Could Stifle Access For Years
39 New Body Blow For Aducanumab As Japan Asks For More Data
39 Aducanumab: Biogen Is The Latest Firm To Preempt A Negative EU Opinion On Approval
40 FDA Grants Breakthrough Therapy Designation For Gantenerumab
40 No REMS Required: Aduhelm’s ARIA Risks, MRI Guidance Conveyed In Labeling, Voluntary Communications
41 Aduhelm’s Revised Labeling Could Help Payers Navigate Reimbursement
41 US FDA Issues Alzheimer’s Disease Breakthrough Therapy Designations
41 Biogen Gets ‘Almost Shockingly Broad’ Label For Alzheimer’s Drug Aducanumab
42 Aducanumab Accelerated Approval Reflects US FDA Flexibility But Raises Doubts About Confirmatory Trial
43 PROBABILITY OF SUCCESS
44 LICENSING AND ASSET ACQUISITION DEALS
44 Merck Takes A New Shot At Alzheimer’s With Cerevance Deal
44 Sosei Bolsters GPCR Focus With AbbVie Neurology Deal
44 AbbVie Gives Up On One Of Alector’s Alzheimer’s Candidates But Plenty More In Pipeline
45 SciNeuro To Revisit GSK’s Work With L-PLA2 Inhibition In Alzheimer’s
45 Cyclica And Arctoris Expand Partnership
45 GliaPharm And Wyss Center Announce Partnership
46 Eisai Gives Full Aduhelm Responsibility To Biogen Under Amended Agreement
46 Zai Lab Pays $35m Up Front For Karuna’s KarXT In Greater China
47 Well-Funded Chinese Venture Races To Clinic Amid Reviving CNS Interest
47 IMM Licenses MultiTEP Platform Technology To NuraVax
47 Sumitomo, Otsuka Both Stand To Gain From CNS Partnership
47 Shape Scores Big Pharma Dollars In Roche Deal For AI-Driven AAV Technology
48 BMS To Increase Focus On Neurology And Neurodegenerative Disease
48 Simcere Acquires License To Develop Vivoryon’s Alzheimer’s Medicines
48 Hoth Therapeutics Signs Sponsored Research Agreement With Washington University
48 Denovo Dusts Down Lundbeck’s Failed Alzheimer’s Drug
49 GSK Looks To Immuno-Neurology In $700m Alector Tie-up
50 CLINICAL TRIAL LANDSCAPE
51 Sponsors by status
52 Sponsors by phase
53 Recent events
61 DRUG ASSESSMENT MODEL
61 Genericized symptomatic treatments
62 Disease-modifying therapies
67 Other pipeline drugs
69 Agitation or psychosis in Alzheimer’s disease
71 MARKET DYNAMICS
72 FUTURE TRENDS
72 Despite setbacks, anti-amyloid antibodies will drive the market, if effective
72 Traditional approvals are necessary for market access
72 Generic symptomatic therapies remain relevant for Alzheimer’s dementia
74 CONSENSUS FORECASTS
77 RECENT EVENTS AND ANALYST OPINION
77 Rexulti for Alzheimer’s Disease (June 27, 2022)
78 Atuzaginstat for Alzheimer’s Disease (January 25, 2022)
79 Atuzaginstat for Alzheimer’s Disease (October 26, 2021)
81 Semorinemab for Alzheimer’s Disease (August 31, 2021)
83 BIIB080 for Alzheimer’s Disease (July 26, 2021)
84 Aduhelm for Alzheimer’s Disease (June 7, 2021)
87 KEY UPCOMING EVENTS
88 UNMET NEEDS
88 Anti-amyloid antibodies need to validate cognitive effect and prolonged survival
88 Symptomatic therapies display modest efficacy at best
88 Beyond cognition and function, Alzheimer’s disease also involves behavioral deficits
89 BIBLIOGRAPHY
90 APPENDIX
LIST OF FIGURES
15 Figure 1: Trends in prevalent cases of Alzheimer’s disease, 2018–27
20 Figure 2: Overview of pipeline drugs for Alzheimer’s disease in the US
20 Figure 3: Pipeline drugs for Alzheimer’s disease, by company
21 Figure 4: Pipeline drugs for Alzheimer’s disease, by drug type
21 Figure 5: Pipeline drugs for Alzheimer’s disease, by classification
43 Figure 6: Probability of success in the Alzheimer’s disease pipeline
50 Figure 7: Clinical trials in Alzheimer’s disease
50 Figure 8: Top 10 drugs for clinical trials in Alzheimer’s disease
51 Figure 9: Top 10 companies for clinical trials in Alzheimer’s disease
51 Figure 10: Trial locations in Alzheimer’s disease
52 Figure 11: Alzheimer’s disease trials status
53 Figure 12: Alzheimer’s disease trials sponsors, by phase
61 Figure 13: Datamonitor Healthcare’s drug assessment summary for Alzheimer’s disease
71 Figure 14: Market dynamics in Alzheimer’s disease
72 Figure 15: Future trends in Alzheimer’s disease
78 Figure 16: Rexulti for Alzheimer’s Disease (June 27, 2022): Phase III – Agitation/Dementia
81 Figure 17: Atuzaginstat for Alzheimer’s Disease (October 26, 2021): Phase II/III – GAIN
83 Figure 18: Semorinemab for Alzheimer’s Disease (August 31, 2021): Phase II – LAURIET (Moderate)
84 Figure 19: BIIB080 for Alzheimer’s Disease (July 26, 2021): Phase I/IIa – MAD
87 Figure 20: Key upcoming events in Alzheimer’s disease (one of two)
87 Figure 21: Key upcoming events in Alzheimer’s disease (two of two)
LIST OF TABLES
9 Table 1: Alzheimer’s disease severity, by rating scale
10 Table 2: FDA stages by disease attributes
13 Table 3: Prevalent cases of Alzheimer’s disease, 2018–27
17 Table 4: Marketed drugs for Alzheimer’s disease
22 Table 5: Pipeline drugs for Alzheimer’s disease in the US
74 Table 6: Historical global sales, by drug ($m), 2017–21
75 Table 7: Forecasted global sales, by drug ($m), 2022–26
77 Table 8: Rexulti for Alzheimer’s Disease (June 27, 2022)
79 Table 9: Atuzaginstat for Alzheimer’s Disease (January 25, 2022)
80 Table 10: Atuzaginstat for Alzheimer’s Disease (October 26, 2021)
82 Table 11: Semorinemab for Alzheimer’s Disease (August 31, 2021)
83 Table 12: BIIB080 for Alzheimer’s Disease (July 26, 2021)
85 Table 13: Aduhelm for Alzheimer’s Disease (June 7, 2021)
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