Alzheimer's Disease Market

• In 2022, the Alzheimer’s disease market size was highest in the US among the 7MM countries, accounting for approximately USD 1,751.7 million. It is expected to increase by 2032.
• The diagnosed prevalence of Alzheimer’s disease has been increasing in the US due to the increasing geriatric population and disease awareness.
• Increased awareness and advancements in a comprehensive understanding of the disease pathophysiology have led to the discovery of novel signaling pathways, due to which various diagnostic tools have evolved that have revolutionized disease diagnosis.
• The current treatment regime is mostly symptomatic, slows disease progression, and helps improve quality of life. It is not curative and is a mix of non-pharmacological and pharmacological approaches.
• Non-pharmacological therapies include cognitive stimulation, physical exercise, and social engagement. Caregiver support and education are crucial for managing the challenges associated with Alzheimer’s.
• The major concern in understanding the market for Alzheimer’s disease is that despite an extremely vibrant pipeline, assessing drugs’ potential to enter the market is difficult due to high failure rates, as many potential therapies like gantenerumab, dabigatran, and verubecestat were unable to move past the trial phase.
• Approval of novel anti-amyloid biologics, which are ‘disease-modifying,’ with novel targeted mechanisms of action, has led to significant improvements from the traditional symptomatic treatment regime. ADUHELM (aducanumab) by Biogen and Eisai was the first available disease-modifying treatment to address Alzheimer’s pathology by targeting amyloid ß plaques, but it has still not received traditional approval in the US, while in Europe and Japan, the drug was rejected, subduing hopes of its success.
• Another amyloid beta-protein inhibitor, LEQEMBI (lecanemab) by Biogen and Eisai, was given accelerated approval by the US FDA in January 2023. In July 2023, the US FDA recently converted this accelerated approval to a traditional one after a confirmatory trial representing a 27% slowing of decline verified the clinical benefits. This marks a major milestone and is a forward-looking step in addressing the unmet needs of patients with early Alzheimer’s. This also paves the way for other biologics and drugs targeting the underlying disease pathology.
• This approval garners well for Biogen and Eisai, keeping them in a profitable position, ensuring a first-mover advantage in the market, and helping them drive past the ADUHELM stumble. There are hopes that it will be Eisai and Biogen’s blockbuster product, and this is further supplemented by a CMS go-ahead with Medicare covering the therapy for Alzheimer’s appropriate patient segment. This will facilitate reimbursement for and access to LEQEMBI. However, certain Medicare requirements and drug labels’ risk warnings and infusion-center bottlenecks could potentially weigh on drug sales, at least in the near term. The testing requirement for a genetic mutation is another hurdle.
• Acetylcholinesterase inhibitors, donepezil, rivastigmine, and galantamine, have comparable efficacy and are widely used to treat mild-to-advanced stages of Alzheimer’s disease, but their benefit-risk ratio is still being debated. NMDA antagonist, memantine, slows symptom progression in individuals with moderate to severe Alzheimer’s disease but is also associated with side effects like dizziness, confusion, etc.
• Emerging Alzheimer's Disease therapies Anavex Life Sciences, Alzheon, Athira Pharma, Annovis Bio, Eli Lilly, BioVie, AB Science, Novo Nordisk, Cassava Sciences, TauRx Therapeutics, KeifeRx, AriBio, Cerecin, Eisai, and others are in late stages of development and have the potential to create a positive shift in the Alzheimer’s market.
• Eli Lilly’s donanemab (LY3002813), an FDA-designated product, is projected to be the first emerging therapy to enter the market by 2024. An amyloid ß protein inhibitor, it will compete with Biogen and Eisai’s LEQEMBI. With one of the best efficacy results, wherein the therapy led to a 39% lower risk of progressing to the next stage of the disease, the drug is projected to have a slow-medium uptake. High costs will translate to higher revenue, and it will attain its peak share by the seventh year. Despite a few products related safety concerns, the drug will perform well during the forecast period.
• BioVie’s NE3107, Cassava Sciences’ simufilam (PTI-125), Anavex Life Sciences’ ANAVEX2-73 (blarcamesine), Alzheon’s ALZ-801 (valiltramiprosate) are next in line with projected entry by 2025. Alzheon’s ALZ-801, another FDA-designated product, is an orally administered amyloid beta-protein and oligomer formation inhibitor. The drug has demonstrated excellent efficacy in its trial, but high doses and long treatment duration may affect the drug’s potential. It will attain its peak share by the eighth year, with a slow-medium uptake.
• Misunderstanding of the disease mechanisms coupled with inconsistent drug development protocols that rely on single-target approaches, in addition to the improper management of drug discovery projects, has contributed to many drug failures in the past. With improvements in disease understanding, there is an opportunity for companies to implement knowledge from recent advances in understanding to evaluate potential drugs with novel targets that are efficacious with a safe profile.

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DelveInsight’s “Alzheimer’s Disease Market Insights, Epidemiology, and Market Forecast 2032” report delivers an in-depth understanding of the Alzheimer’s disease historical and forecasted epidemiology as well as the market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.

The Alzheimer’s disease market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted 7MM Alzheimer’s disease market size from 2019 to 2032. The report also covers current Alzheimer’s disease treatment practices/algorithms and unmet medical needs to curate the best opportunities and assess the market’s potential.

Geography Covered

• The United States
• EU4 (Germany, France, Italy, and Spain) and the United Kingdom
• Japan

Study Period: 2019–2032

Alzheimer’s Disease Understanding and Treatment Algorithm

Alzheimer’s Disease Overview

Alzheimer’s disease, the most common type of dementia, is a progressive neurodegenerative disorder with a multifactorial pathogenesis. It is characterized by the gradual decline in cognitive and functional abilities, with individuals eventually losing the ability to undertake everyday tasks and function independently. Symptoms, for most people, first appear in their mid-60s. However, early disease may manifest in quadragenarians as well.

Although the symptoms vary widely, they typically develop slowly and worsen over time. Early signs may include forgetfulness, difficulty with problem-solving or completing familiar tasks, confusion, disorientation, and changes in mood or behavior. As the disease progresses, individuals may experience severe memory loss, language problems, impaired judgment, personality changes, and a decline in overall cognitive abilities.

Improved disease understanding demonstrates that two microscopic features, amyloid plaques and neurofibrillary agglomerates, characterize the disease. The exact cause is mostly unknown, but research indicates that progressive cognitive decline is associated with the accumulation of amyloid-beta (Aß) and tau proteins. These deposits form amyloid protein plaques outside the brain cells and tangles of tau protein within the brain cells.

These plaques and tangles disrupt normal communication between brain cells, leading to progressive degeneration, memory deterioration, and death. Increasing age and family history are important risk factors.

The disease progresses through several stages with a corresponding increase in severity. The preclinical stage is mostly asymptomatic, while in the next mild cognitive impairment stage, an individual may experience mild memory problems, but this may not significantly affect daily functioning, and some individuals with MCI may not progress to Alzheimer’s disease. Mild, moderate, and severe stages are associated with progressive deterioration of memory that affects language, personality, or cognitive control, with symptoms interfering with daily life. Mild Alzheimer’s disease is when symptoms start interfering with daily life. Further, moderate Alzheimer’s disease can last for years making symptoms more pronounced and assistance with daily activities become necessary. In the last stage, i.e., severe Alzheimer’s disease, individuals lose the ability to communicate verbally, recognize their loved ones, and carry out basic tasks. The risk of infections and other complications increases, leading to a further decline in health.

Alzheimer’s Disease Diagnosis

The pathogenesis is multifactorial, and due to the continuous discovery of novel signaling pathways, various diagnostic tools have revolutionized and improved disease diagnosis making it more personalized. This has helped me understand the various possibilities of tau and amyloid deposition, neurodegeneration, and symptom manifestation.

Diagnosing Alzheimer’s disease involves a comprehensive evaluation of medical history, cognitive tests, neurological exams, and assessment of behavioral and functional changes. There is no single test for the diagnosis. In clinical practice, it is typically diagnosed by a multi-disciplinary workup based on patient history, clinical symptoms, and various neuropsychiatric, physical, and functional assessments. Imaging (computed tomography, magnetic resonance imaging (MRI), positron emission tomography (PET) assessments, and blood tests are particularly important to rule out certain other causes of dementia. PET scans, especially amyloid scans, fluorodeoxyglucose imaging, and tau imaging, besides CSF biomarkers and blood-biomarker-based diagnosis, have improved the diagnosis manifold

For cognitive and functional assessment, standardized tests such as the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA) are commonly used. The diagnostic guideline provided by National Institute on Aging (NIA), called NIA-AA criteria, is the most accepted.

Earlier diagnosis of AD is important to enable symptomatic therapies, treat behavioral symptoms, and adopt lifestyle changes that are used more commonly worldwide to reduce the risk of developing dementia and, eventually, to slow disease progression.

Further details related to country-based variations are provided in the report…

Alzheimer’s Disease Treatment

There is no cure for Alzheimer’s disease, and the available treatments offer relatively small symptomatic benefits but remain palliative. The treatment is divided into pharmaceutical, psychosocial, and caregiving.

Psychosocial interventions are adjuncts to pharmaceutical treatment and are classified within behavior, emotion, cognition, or stimulation-oriented approaches. Cognitive stimulation therapy (CST), cognitive rehabilitation, simulated presence therapy, and music therapy effectively reduce behavioral and psychological symptoms.

Environment and lifestyle modifications, diet, and behavioral interventions are also important to improve the quality of life.

The drugs currently available to treat many of the symptoms associated with dementia are working by increasing activity levels of some brain neurotransmitters, such as acetylcholine, serotonin, and noradrenaline, or by reducing the activity of other neurotransmitters, such as glutamate and dopamine.

Pharmacological therapies for symptomatic treatment, such as acetylcholinesterase inhibitors (AChEIs), and NMDA receptor antagonist, memantine, have been available for over a decade. Recently, more targeted monoclonal antibodies that target amyloid beta-proteins have entered the Alzheimer’s market space.

Donepezil, rivastigmine transdermal patch, and galantamine are three AChEIs approved for treating Alzheimer’s disease. These are recommended to treat mild-to-advanced stages of Alzheimer’s disease, yet their benefit-risk ratio is still being debated, with many countries not allowing their reimbursement.

Besides these, NMDA receptor antagonists, NAMENDA and NAMZARIC, have also been approved for treating Alzheimer’s disease but are limited to moderate and severe cases and mostly in cases where cholinesterases have not been effective. Of the two, the former is a monotherapy, while the latter is a combination product with an acetylcholinesterase inhibitor. Atypical antipsychotics, though not approved, are even commonly used to treat behavioral symptoms associated with Alzheimer’s disease.

In June 2021, Biogen and Eisai’s ADUHELM (aducanumab) received accelerated approval from the US FDA for the treatment of people living with early Alzheimer’s disease, including people with mild cognitive impairment due to Alzheimer’s disease, making it the first available disease-modifying treatment to address AD pathology by targeting amyloid ß plaques. However, the drug is not globally accessible, as it did not receive approval by the EMA or MHLW, and the AD community is still awaiting further trial data to support its approval.

Another Alzheimer’s medicine, LEQEMBI (lecanemab) by Biogen and Eisai, was given accelerated approval by the US FDA in January 2023. Recently in July 2023, the US FDA converted accelerated approval to traditional approval following a determination that a confirmatory trial verified clinical benefit. LEQEMBI is the first amyloid beta-directed antibody targeting the disease process to be converted from accelerated approval to traditional approval. This garners well for the drug, which during the forecast period may drive past ADUHELM and keep Biogen and Eisai at an advantageous position in the market, which needs a disease-modifying therapy. The company has also submitted an application to the European Medicines Agency (EMA) for approval of lecanemab in the EU. However, their efficacy is limited, and they have serious adverse events like edema and hemorrhage.

Alzheimer’s Disease Epidemiology

As the market is derived using a patient-based model, the Alzheimer’s disease epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by total diagnosed prevalent cases of Alzheimer’s disease, age-specific cases of Alzheimer’s disease, gender-specific cases of Alzheimer’s disease, and severity-specific cases of Alzheimer’s disease in the 7MM covering the United States, EU4 countries (Germany, France, Italy, and Spain) and the United Kingdom, and Japan from 2019 to 2032.

• In 2022, the total diagnosed prevalent cases of Alzheimer’s disease were estimated to be approximately 15,083,370 cases in the 7MM. These cases are projected to increase at a CAGR of 2.4%.
• In the US, there were approximately 6,186,284 diagnosed prevalent cases of Alzheimer’s disease in 2022. These were nearly 41% of the total cases in the 7MM. These cases are expected to increase during the forecast period.
• In 2022, among the 7MM, Japan accounted for the second-highest diagnosed prevalent cases of Alzheimer’s disease, contributing nearly 26%, while the UK accounted for the least with nearly 4% of the total diagnosed prevalent cases.
• In 2022, EU4 and the UK accounted for nearly 33% of the total diagnosed prevalent cases of Alzheimer’s in the 7MM. There were approximately 4,942,376 total diagnosed prevalent cases of Alzheimer’s disease.
• Among EU4 and the UK, Germany accounted for the highest (nearly 31%) total diagnosed prevalent cases of Alzheimer’s disease, with approximately 1,510,515 cases, followed by France (nearly 24%).
• Japan accounted for 3,954,710 diagnosed prevalent cases of Alzheimer’s disease. In 2022 the age-specific distribution of the disease suggests that the age cohort of 75–84 years accounted for the majority, nearly 51% of the cases, followed by =85 (32%), 65–74 (14%), and <65 years (3%). These cases of Alzheimer’s disease are expected to increase during the forecast period.
• As per estimates based on DelveInsight’s epidemiology model for Alzheimer’s disease, the gender distribution of the disease suggests a female predominance across the 7MM, with approximately 5,024,849 male and 10,058,521 female cases in the 7MM in 2022.
• According to estimates based on DelveInsight’s epidemiology model, in EU4 and the UK, around 1,454,541 males and 3,487,835 females were diagnosed with Alzheimer’s disease in 2022, and the cases are expected to increase during the forecast period.
• According to estimates based on DelveInsight’s epidemiology model for Alzheimer’s disease, in Japan, in 2022, there were approximately 2,324,183 cases of MCI, 826,139 cases of mild dementia, 517,671 cases of moderate dementia, and 286,716 cases of severe dementia, which are expected to increase during the study period.

Alzheimer’s Disease Drug Chapters

The drug chapter segment of the Alzheimer’s disease report encloses a detailed analysis of Alzheimer’s disease – currently used drugs and mid-stage (Phase II and Phase I) pipeline drugs. It also helps understand the Alzheimer’s disease clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug, and the latest news and press releases.

Marketed Alzheimer’s disease Drugs

ADUHELM (aducanumab): Biogen and Eisai

In June 2021, Biogen and Eisai’s ADUHELM (aducanumab) received accelerated approval from the US FDA for the treatment of people living with early Alzheimer’s disease, including people with mild cognitive impairment due to Alzheimer’s disease, making it the first available disease-modifying treatment to address Alzheimer’s disease pathology by targeting amyloid ß plaques.

However, the drug is not globally accessible, as it did not receive approval by the EMA or MHLW, and the Alzheimer’s community is still awaiting further trial data to support its approval.

It exerts its mechanism of action by crossing the blood-brain barrier and selectively targeting and binding aggregated soluble oligomers and insoluble fibril conformations of Aß plaques in the brain. In September 2016, the US FDA granted Fast Track Designation (FTD) to Biogen’s aducanumab to treat Alzheimer’s disease.

LEQEMBI (lecanemab): Biogen and Eisai

In July 2023, the US FDA converted accelerated approval to traditional approval following a determination that a confirmatory trial verified clinical benefit. LEQEMBI is the first amyloid beta-directed antibody targeting the disease process to be converted from accelerated approval to traditional approval. LEQEMBI (lecanemab) was given accelerated approval by the US FDA in January 2023 for treating people with mild Alzheimer’s disease and mild cognitive impairment due to Alzheimer’s disease.

Biogen and Eisai have submitted an application to the European Medicines Agency (EMA) for approval of lecanemab in the EU and have also been designated for priority review by the Japanese Ministry of Health, Labour, and Welfare. This approval fares well, as it also received the CMS go-ahead, and Medicare will cover this therapy for Alzheimer’s appropriate patient segment.

It is a humanized IgG1 monoclonal antibody directed against aggregated soluble (protofibrils) and insoluble forms of Aß. The accumulation of amyloid beta plaques in the brain is a defining pathophysiological feature of Alzheimer’s disease. LEQEMBI reduces amyloid beta plaques. The US FDA has granted the drugs breakthrough therapy designation and FTD.

Also Read | Leqembi: A New Hope for Alzheimer’s Disease Patients

Emerging Alzheimer’s disease Drugs

NE3107: BioVie

NE3107, being developed by BioVie, is an oral, small molecule, blood-brain permeable, anti-inflammatory, insulin sensitizer that binds to extracellular signal-regulated kinase (ERK) and selectively inhibits inflammation. NE3107 inhibits extracellular ERK/NFkB activation and TNF production stimulated by inflammatory mediators, such as lipopolysaccharide, and inhibits NFkB activation and TNF production. BioVie is also developing a drug for treating Parkinson’s disease, multiple myeloma, and prostate cancer. The company is currently conducting Phase III trials to treat mild to moderate Alzheimer’s disease.

Donanemab (LY3002813): Eli Lilly

Donanemab (LY3002813), being developed by Eli Lilly and Company, is a humanized IgG1 monoclonal antibody N3pG, developed from mouse mE8-IgG2a that identifies and destroys Aß proteins, excess abnormal proteins that bind together to create brain plaques in Alzheimer’s disease patients. The rationale behind donanemab is that targeting deposited plaque itself is necessary to clear existing amyloid burden from the brain rather than merely prevent the deposition of new plaques or the growth of existing plaques.

Given via the IV administration route, its Phase III trial was recently completed. The confirmatory Phase III TRAILBLAZER-ALZ 2 trial is ongoing, with topline data read-out expected in Q2 2023, and will form the basis of donanemab's application for traditional approval.

Also Read | Donanemab: Will the Therapy be the Next Imminent Breakthrough in the Alzheimer’s Disease Treatment Landscape?

Simufilam (PTI-125): Cassava Sciences

Simufilam (PTI-125), being developed by Cassava Sciences, is a small-molecule drug candidate that binds and reverses an altered conformation of the scaffolding protein filamin A (FLNA), a ubiquitous scaffolding protein and regulator of the actin cytoskeleton in the Alzheimer’s disease brain. Filamin has been reported to stabilize the high-affinity interaction of soluble Aß42 and the alpha7 nicotinic acetylcholine receptor (a7nAChR), which has been reported to trigger tau phosphorylation and synaptic dysfunction. It is to be administered through the oral route, improving the function of multiple brain receptors and exerting powerful anti-neuroinflammatory effects.

Cassava Sciences is evaluating simufilam tablets for Alzheimer’s disease in two Phase III clinical studies and anticipates the completion of patient enrollment for both studies by year-end 2023.

Hydromethylthionine mesylate/TRx0237: TauRx Therapeutics

TauRx Therapeutic’s Hydromethylthionine mesylate (TRx0237) is an orally active second-generation tau protein aggregation inhibitor (TAI). It is a small molecule drug being tested for its ability to inhibit aggregation of tau (a protein) that forms neurofibrillary tangles in the brains of people with Alzheimer’s disease and other neurodegenerative diseases.

It has already completed three separate Phase III trials, and data on completing the 24-month study is expected in mid-2023. TauRx plans to submit for regulatory approval in the UK, US, and Canada in 2023.

ALZ-801 (valiltramiprosate): Alzheon

Alzheon’s ALZ-801 (valiltramiprosate) is a small oral molecule that fully blocks the formation of neurotoxic soluble amyloid oligomers in the brain. ALZ-801 is a valine-conjugated prodrug of tramiprosate and is converted to homotaurine in vivo, but it is more easily absorbed and lasts longer in the blood than tramiprosate. ALZ-801 and tramiprosate are metabolized to 3-sulfopranpanoic acid (3-SPA), which is normally found in the brain and inhibits Aß42 aggregation. It is an improved prodrug of tramiprosate. The US FDA has granted it FTD. It is being evaluated in Phase III to treat early Alzheimer’s disease.

Fosgonimeton (ATH-1017): Athira Pharma

Athira Pharma’s fosgonimeton (ATH-1017) is a small molecule designed to enhance the activity of hepatocyte growth factor (HGF) and its receptor, MET, to impact neurodegeneration and regenerate brain tissue. The function of the HGF/MET receptor system may be impaired in the brain under neurodegeneration conditions. HGF is a potent neurotrophic factor active in many cell types of the CNS. HGF activity, through the receptor tyrosine kinase MET, promotes survival and regeneration in various neuron types, including hippocampal, midbrain dopaminergic, cortical, motor, sensory, and cerebellar granular neurons. HGF signaling is also active in glial cells.

The drug has completed a Phase II study and is undergoing Phase II/III clinical trials in subjects with mild-to-moderate Alzheimer’s disease, with topline results expected by early 2024.

Buntanetap: Annovis Bio

Buntanetap (previously known as ANVS401 or posiphen) is an orally bioavailable small molecule derived via a synthetic biochemical pathway. It is a translational inhibitor of neurotoxic aggregating proteins (TINAPs). It offers a transformative and superior mechanism to treat neurodegenerative disorders. It is being developed for Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative conditions such as Alzheimer’s in Down syndrome. It is currently being evaluated in a Phase II/III study to assess its efficacy in mild-to-moderate Alzheimer’s disease patients.

ANAVEX2-73 (blarcamesine): Anavex Life Sciences

ANAVEX2-73 (blarcamesine) is a small molecule oral therapy being developed by Anavex Life Sciences that activates SIGMAR1, a stress-reducing survival protein located on the endoplasmic reticulum membrane of cells, receptor agonist, and muscarinic receptor modulator with a strong safety record and preliminary evidence of efficacy in patients with MCI due to Alzheimer’s disease and mild Alzheimer’s disease.

It is thought to help restore cellular balance by targeting protein misfolding (when proteins fail to fold correctly into a normal configuration, they do not work as intended), oxidative stress (which damages cells due to oxygen molecules with free radicals or unpaired electrons), mitochondrial dysfunction, inflammation, and cellular stress.

It has completed Phase IIb/III trials for Alzheimer has and is currently conducting an open-label extension study.

Note: Detailed emerging therapies assessment will be provided in the final report.

Alzheimer’s disease Drug Class Insights

Alzheimer’s disease, the most common type of dementia, is a progressive neurodegenerative disorder with a multifactorial pathogenesis. It is characterized by a gradual decline in cognitive and functional abilities, with individuals eventually losing the ability to undertake everyday tasks and function independently. Symptoms of Alzheimer’s disease, for most people, first appear in their mid-60s. However, early disease may manifest in quadragenarians as well. Early diagnosis becomes difficult with the exact cause mostly unknown and limited early manifestation. The multifactorial nature of the disease further compounds this. Earlier diagnosis is important for enabling symptomatic therapies, treating behavioral symptoms, and adopting lifestyle changes.

The current treatment regime is mostly symptomatic, slows disease progression, and helps improve quality of life. It is not curative and is a mix of non-pharmacological and pharmacological approaches. Most drugs available to treat symptoms work by increasing activity levels of some brain neurotransmitters, such as acetylcholine, serotonin, and noradrenaline, or by reducing the activity of other neurotransmitters, such as glutamate and dopamine.

Pharmacological therapies for symptomatic treatment, such as acetylcholinesterase inhibitors (AChEIs), and NMDA receptor antagonist, memantine, have been available in the US for over a decade. Recently, more targeted monoclonal antibodies that target amyloid beta-proteins have entered the Alzheimer’s market space.

The US FDA and EMA approved three AChEIs, donepezil, rivastigmine, and galantamine, with comparable therapeutic effects. These are recommended to treat mild-to-advanced stages of Alzheimer’s disease, yet their benefit-risk ratio is still being debated. They work by inhibiting the activity of acetylcholinesterase, an enzyme that breaks down acetylcholine, a neurotransmitter involved in memory and cognitive function. By inhibiting acetylcholinesterase, these medications increase the levels of acetylcholine in the brain, potentially improving cognitive symptoms in Alzheimer’s disease.

The NMDA antagonist, memantine, is recommended for moderate to severe Alzheimer’s and slows disease progression. It can be given as monotherapy or combined with a cholinesterase inhibitor. This class of drugs is recommended for patients with an established Alzheimer’s diagnosis where AChE inhibitors are already used. It is not typically used as a first-line treatment for mild Alzheimer’s. In Alzheimer’s disease, N-methyl-D-aspartate (NMDA) receptors are excessively activated by the neurotransmitter glutamate. This overstimulation can lead to nerve cell damage and cognitive decline. Memantine works by blocking the excessive activity of glutamate at NMDA receptors, helping to regulate the neurotransmitter’s effects and potentially slowing down cognitive decline. Although they are generally well-tolerated, they have side effects like dizziness, headache, constipation, confusion, fatigue, and agitation.

With the improved pathological understanding of Alzheimer’s and the discovery of new therapeutic targets, novel monoclonal antibodies that target amyloid beta-proteins have been approved in the last couple of years. In June 2021, Biogen and Eisai’s ADUHELM (aducanumab) received accelerated approval from the US FDA to treat people living with early Alzheimer’s disease. LEQEMBI (lecanemab) by Biogen and Eisai is another amyloid beta inhibitor that has received approval but is the only one to receive traditional approval. Amyloid beta-protein (Aß) is a peptide that accumulates and forms plaques in the brains of individuals with Alzheimer’s disease. These plaques are one of the hallmark pathological features of the disease. The accumulation of Aß, particularly in its aggregated form, is believed to contribute to the neurodegeneration and cognitive decline seen in Alzheimer’s.

Though there has been considerable research and development in the area of amyloid beta-protein inhibitors, the results have been mixed. Some clinical trials have not shown significant benefits in terms of cognitive improvement or disease modification. The complex nature of Alzheimer’s disease and the involvement of multiple pathological processes make it a challenging condition to target with a single therapy.

Alzheimer’s Disease Market Outlook

The drugs currently available to treat many of the symptoms associated with dementia are working by increasing activity levels of some brain neurotransmitters, such as acetylcholine, serotonin, and noradrenaline, or by reducing the activity of other neurotransmitters, such as glutamate and dopamine. Due to associated side effects, it is also important to personalize dementia symptomatic therapeutics considering patients’ comorbidities and their respective therapies. Effects on cardiac function, drug elimination, and other interactions should be assessed case by case.

According to a study by Podhorna et al. (2020), globally, Alzheimer’s disease-specific pharmacotherapy was the predominant treatment option, even in patients with MCI or prodromal Alzheimer’s disease, with 44% of patients with MCI/prodromal Alzheimer’s disease, 71% of patients with mild disease and 76% of patients with moderate disease receiving any Alzheimer’s disease-specific pharmacologic treatment.

Pharmacological therapies for symptomatic treatment, such as acetylcholinesterase inhibitors (AChEIs), and NMDA receptor antagonist, memantine, have been available in the US for over a decade.

The US FDA and the EMA have approved three AChEIs. They are used in more than 60 countries to treat mild-to-advanced stages of Alzheimer’s disease. These are donepezil, rivastigmine transdermal patch, and galantamine. The therapeutic effects of donepezil, rivastigmine, and galantamine are fairly comparable. Their effectiveness is considered modest and temporary and needs to be regularly re-evaluated. Though these have demonstrated symptomatic benefits in rigorous double-blind, placebo-controlled randomized clinical trials, there are also associated side effects. However, their benefit-risk ratio is still being debated, due to which some countries, notably France, have chosen not to allow their reimbursement by the public health sector.

The NMDA antagonist, memantine, works in another brain cell communication network and slows the progression of symptoms in individuals with moderate to severe Alzheimer’s disease. It can be given as monotherapy or combined with a cholinesterase inhibitor.

The NICE guidelines on Dementia in England recommends acetylcholinesterase (AChE) inhibitors: donepezil, galantamine, and rivastigmine as monotherapies for managing mild to moderate Alzheimer’s disease. It also recommends that the NMDA receptor antagonist, memantine, be used to treat moderate Alzheimer’s disease in patients who are intolerant or have a contraindication to AChE inhibitors. Memantine is also recommended for patients with an established Alzheimer’s disease diagnosis when AChE inhibitors are already used.

With an improved understanding of Alzheimer’s disease, a pathological cascade of amyloid-ß deposition, tau-hyperphosphorylation, neurofibrillary tangle formation, inflammation, synaptic and cell loss has been well documented. Biogen and Eisai developed ADUHELM (aducanumab) and LEQEMBI (lecanemab) as anti-amyloid therapies. Of these former could not get traditional approval, but recently LEQEMBI received US FDA approval. Hopefully, it will change the market dynamics and make Biogen and Eisai key players. This approval of a disease-modifying therapy is a ray of hope for many early-stage Alzheimer’s patients. But a testing requirement on the drug’s prescribing label could be a potential hurdle. The FDA recommends doctors test patients for a genetic mutation known as ApoE4 before starting treatment.

The current market has been covered by the symptomatic treatment that includes different pharmacological agents used across the 7MM, which presents minor variations in the overall prescription pattern. ADUHELM (aducanumab), LEQEMBI (lecanemab), galantamine, rivastigmine, donepezil, memantine, and combination (memantine with acetylcholinesterase inhibitors) are the major drugs considered for symptomatic treatment in the forecast model.

Key players Anavex Life Sciences, Alzheon, Athira Pharma, Annovis Bio, Eli Lilly, BioVie, AB Science, Novo Nordisk, Cassava Sciences, TauRx Therapeutics, KeifeRx, AriBio, Cerecin, Eisai, and others are evaluating their lead candidates in different stages of clinical development. They aim to investigate their products for the treatment of Alzheimer’s Disease.

• The total Alzheimer’s disease market size in the 7MM was approximately USD 3,460.6 million in 2022 and is projected to increase during the forecast period (2023–2032).
• According to DelveInsight’s estimates, among the 7MM, the US had the largest Alzheimer’s disease market share, with a revenue of USD 1,751.7 million in 2022. The Alzheimer’s disease market size in the US will increase at a significant CAGR due to increasing awareness of the disease and the launch of the emerging therapy.
• The total Alzheimer’s disease market size in EU4 and the UK was calculated to be USD 794.4 million in 2022, which was approximately 23.0% of the total market revenue for the 7MM. Among EU4 and the UK countries, Germany accounted for the maximum Alzheimer’s disease market size in 2022, while the UK occupied the bottom of the ladder.
• Japan accounted for the second largest Alzheimer’s disease market among the 7MM, with a revenue of approximately USD 914.5 million in 2022, expected to increase during the forecast period.
• As per DelveInsight’s estimates, in the 7MM, cholinesterase inhibitors and NMDA receptor antagonists accounted for USD 3,210.9 million and USD 245.0 million in 2022. Among cholinesterase, donepezil had the highest share (of all the therapies), with nearly 54% of the total revenue in the class, while rivastigmine generated USD 946.1 million in 2022.
• DelveInsight estimates that ADUHELM accounted for USD 4.6 million in the US in 2022. This revenue is projected to increase with hopes for traditional approval.
• According to DelveInsight’s estimates, Biogen and Eisai’s LEQEMBI, which received approval from the US FDA in July 2023, though it may have a humble start, is projected to grow substantially during the forecast period, providing the company a substantial advantage in the biologic pie of the Alzheimer Disease market.
• Various therapies like Anavex Life Sciences’s ANAVEX2-73 (blarcamesine), Alzheon’s ALZ-801 (valiltramiprosate), Athira Pharma’s fosgonimeton (ATH-1017), Annovis Bio’s buntanetap, Eli Lilly’s donanemab (LY3002813), BioVie’s NE3107, Cassava Sciences’ simufilam (PTI-125), and TauRx Therapeutics’ hydromethylthionine mesylate (TRx0237) among others are anticipated to enter the market during the forecast period.
• Eli Lilly’s donanemab (LY3002813), an FDA-designated product, is projected to be the first emerging therapy to enter the market by 2024. An amyloid ß protein inhibitor, it will compete with Biogen and Eisai’s LEQEMBI. With one of the best efficacy results, wherein the therapy led to a 39% lower risk of progressing to the next stage of the disease, the drug is projected to have a slow, medium uptake. High costs will translate to higher revenue, and it will attain its peak share by the seventh year. Despite a few products related safety concerns, the drug will perform well during the forecast period.
• Another molecule to enter the same year is a tau aggregation inhibitor by TauRx Therapeutics. Hydromethylthionine mesylate (TRx0237), an orally administered therapy for early Alzheimer’s, has reported no safety issues. It is the first novel target drug that is not biological and has the potential to be one of the best performers.
• BioVie’s NE3107, Cassava Sciences’ simufilam (PTI-125), Anavex Life Sciences’ ANAVEX2-73 (blarcamesine), Alzheon’s ALZ-801 (valiltramiprosate) are next in line with projected entry by 2025. Alzheon’s ALZ-801, another FDA-designated product, is an orally administered amyloid beta-protein and oligomer formation inhibitor. The drug has demonstrated excellent efficacy in its trial, but high doses and long treatment duration may affect its potential. With a slow-medium uptake, it will attain its peak share by the eighth year.
• Anavex Life Sciences’ ANAVEX2-73 (blarcamesine), a SIGMAR1 activator and muscarinic receptor modulator for treating early Alzheimer’s patients, has the potential to establish itself in the crowded market space. The trials have demonstrated that about 84% of the treated patients have improved cognition. A low-dose regime might ensure better compliance. All these factors point to the drug performing well in the Alzheimer’s market. The drug will peak by the eighth year with a medium uptake.
• Athira Pharma’s fosgonimeton (ATH-1017), a hepatocyte growth factor and MET receptor stimulant, has demonstrated excellent improvements in cognitive score in its trial. A low dose favorable safety profile places the drug in a strong position, which is anticipated to have a medium uptake.

Alzheimer’s Disease Drugs Uptake

This section focuses on the uptake rate of potential drugs expected to be launched in the market during 2019–2032. For example, Annovis Bio’s buntanetap, a translational inhibitor of neurotoxic aggregating proteins, with an anticipated entry by 2027 in the US, is predicted to have a slow-medium uptake during the forecast period.

Further detailed analysis of emerging therapies drug uptake in the report…

Alzheimer’s Disease Pipeline Development Activities

The report provides insights into therapeutic candidates in Phase II and Phase I. It also analyzes key players involved in developing targeted therapeutics.

Pipeline Development Activities

The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for emerging therapies for Alzheimer’s disease.

KOL Views

To keep up with current market trends, we take KOLs and SMEs’ opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry Experts contacted for insights on the Alzheimer’s disease evolving treatment landscape, patient reliance on conventional therapies, patient therapy switching acceptability, and drug uptake, along with challenges related to accessibility, including Medical/scientific writers, Medical Professionals, Professors, Directors, and Others.

DelveInsight’s analysts connected with 50+ KOLs to gather insights; however, interviews were conducted with 15+ KOLs in the 7MM. Centers like Southern Illinois University School of Medicine, the University of Washington, the University Hospital of Tours, Navarra Institute for Health Research, the University of Tokyo School of Medicine, and the National Center of Neurology and Psychiatry were contacted. Their opinion helps understand and validate current and emerging therapy treatment patterns or Alzheimer’s disease market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

Physician’s View

According to the primary research analysis, LEQEMBI’s approval will change the treatment regime and market dynamics for Alzheimer’s. Though not curative, this first approved disease-modifying therapy garners well for early Alzheimer’s patients, as it delays the progression. Though the drug has potential, there are certain hurdles, like testing requirements on the drug’s prescribing label and risk warning, which push one to keep caution. The results in delaying disease progression have done well, and awareness needs to be generated to ensure drug usage.

Qualitative Analysis

We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT and Conjoint Analysis. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of disease diagnosis, patient awareness, patient burden, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided. These pointers are based on the Analyst’s discretion and assessment of the patient burden, cost analysis, and existing and evolving treatment landscape.

Conjoint Analysis analyzes multiple emerging therapies based on relevant attributes such as safety, efficacy, frequency of administration, route of administration, and order of entry. To analyze the effectiveness of these therapies, have calculated their attributed analysis by giving them scores based upon change from baseline in the ADCS-ADL scale, ADAS-Cog scale, and Clinical Dementia Rating (CDR) - global score results, among others. Scoring is given based on these parameters to analyze the effectiveness of therapy.

The therapies’ safety is evaluated wherein treatment-related adverse events along with serious adverse events were majorly observed, besides the occurrence of amyloid-related imaging abnormalities (ARIA). It sets a clear understanding of the side effects posed by the drug in the trials. In addition, the scoring is also based on the route of administration, order of entry and designation, probability of success, and the addressable patient pool for each therapy. According to these parameters, the final weightage score and the ranking of the emerging therapies are decided.

Alzheimer’s disease Market Access and Reimbursement

In April 2022, CMS released its final national coverage determination (NCD) decision memorandum on Medicare coverage for approved mAbs as a treatment for Alzheimer’s disease. CMS issued a two-track decision that differentiates Medicare coverage for mAbs based on whether they receive from the US FDA: Accelerated approval based on surrogate endpoints or traditional approval based on clinical endpoints.

According to the NCD decision, Medicare will not cover mAbs directed against amyloid for treating Alzheimer’s when provided outside of randomized controlled trials conducted under an FDA IND, CMS-approved studies, or NIH-supported studies. Medicare would also not provide coverage when the trial investigates the drug in a way that is not according to the current FDA label. Further, when the FDA updates the label, CMS will re-evaluate the coverage policy accordingly.

Lecanemab received accelerated approval as a treatment for early Alzheimer’s from the US FDA; hence, the NCD policy also applies to lecanemab blocking its Medicare coverage.

On January 2023, CMS rejected a petition to provide wider coverage for LEQEMBI on Medicare. It also stated that because Eisai’s product, lecanemab, was granted accelerated approval by the FDA, it falls under CMS’s existing national coverage determination. Additionally, CMS mentioned that if lecanemab subsequently receives traditional FDA approval, CMS would provide broader coverage.

In July 2023, the US FDA approved the sBLA supporting the traditional approval of LEQEMBI (lecanemab) 100 mg/mL injection for IV use. Following FDA’s traditional approval Medicare will cover the therapy for appropriate patients. This will facilitate reimbursement for and access to LEQEMBI across a broad range of healthcare settings in the US.

The report provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenarios, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc.

Scope of the Alzheimer’s disease Report

• The report covers a segment of key events, an executive summary, descriptive overview of Alzheimer’s disease, explaining its causes, signs and symptoms, pathogenesis, and currently available therapies.
• Comprehensive insight into the epidemiology segments and forecasts, the future growth potential of diagnosis rate, disease progression, and treatment guidelines have been provided.
• Additionally, an all-inclusive account of the current and emerging therapies and the elaborative profiles of late-stage and prominent therapies will impact the current treatment landscape.
• A detailed review of the Alzheimer’s disease market, historical and forecasted market size, market share by therapies, detailed assumptions, and rationale behind the approach is included in the report, covering the 7MM drug outreach.
• The report provides an edge while developing business strategies, by understanding trends, through SWOT analysis and expert insights/KOL views, patient journey, and treatment preferences that help shape and drive the 7MM Alzheimer’s disease market.

Alzheimer’s Disease Market Report Insights

• Alzheimer’s disease Patient Population
• Therapeutic Approaches
• Alzheimer’s Disease Pipeline Analysis
• Alzheimer’s Disease Market Size and Trends
• Existing and Future Alzheimer’s disease Market Opportunity

Alzheimer’s Disease Report Key Strengths

• Ten Years Forecast
• The 7MM Coverage
• Alzheimer’s Disease Epidemiology Segmentation
• Key Cross Competition
• Conjoint analysis
• Alzheimer’s disease Drugs Uptake
• Key Alzheimer’s disease Market Forecast Assumptions

Alzheimer’s Disease Market Report Assessment

• Current Alzheimer’s disease Treatment Practices
• Alzheimer’s disease Unmet Needs
• Alzheimer’s disease Pipeline Product Profiles
• Alzheimer’s disease Market Attractiveness
• Qualitative Analysis (SWOT and Conjoint Analysis)

Key Questions

Alzheimer’s disease Market Insights

• What was the total Alzheimer’s disease market size, the market size of Alzheimer’s disease by therapies, market share (%) distribution in 2019, and what would it look like by 2032? What are the contributing factors for this growth?
• How will donanemab (LY3002813), hydromethylthionine mesylate (TRx0237), ALZ-801 (valiltramiprosate), fosgonimeton (ATH-1017) and others affect the treatment paradigm of Alzheimer’s disease?
• How will LEQEMBI (lecanemab) compete with other off-label symptomatic treatments?
• Which drug is going to be the largest contributor by 2032?
• What are the pricing variations among different geographies for off-label therapies?
• How would future opportunities affect the market dynamics and subsequent analysis of the associated trends?

Alzheimer’s disease Epidemiology Insights

• What are the disease risk, burdens, and unmet needs of Alzheimer’s disease? What will be the growth opportunities across the 7MM with respect to the patient population pertaining to Alzheimer’s disease?
• What is the historical and forecasted patient pool of Alzheimer’s disease in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan?
• Out of the countries mentioned above, which country would have the highest diagnosed Alzheimer’s disease diagnosed prevalent population during the forecast period (2023–2032)?
• What factors are contributing to the growth of Alzheimer’s disease cases?

Current Treatment Scenario, Marketed Drugs, and Emerging Therapies

• What are the current options for the treatment of Alzheimer’s disease?
• How many companies are developing therapies for the treatment of Alzheimer’s disease?
• How many emerging therapies are in the mid-stage and early stage of development for treating Alzheimer’s disease?
• What are the recent novel therapies, targets, mechanisms of action, and technologies developed to overcome the limitation of existing Alzheimer’s disease therapies?
• What is the cost burden of current treatment on the patient?
• Patient acceptability in terms of preferred treatment options as per real-world scenarios?
• What are the accessibility issues of approved therapy in the US?
• What is the 7MM historical and forecasted Alzheimer’s disease market?

Reasons to Buy

• The report will help develop business strategies by understanding the latest trends and changing treatment dynamics driving the Alzheimer’s disease market.
• Insights on patient burden/disease prevalence, evolution in diagnosis, and factors contributing to the change in the epidemiology of the disease during the forecast years.
• Understand the existing market opportunity in varying geographies and the growth potential over the coming years.
• The distribution of historical and current patient share based on real-world prescription data in the US, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.
• Identifying strong upcoming players in the market will help devise strategies to help get ahead of competitors.
• Detailed analysis and ranking of class-wise potential current and emerging therapies under the conjoint analysis section to provide visibility around leading classes.
• To understand Key Opinion Leaders’ perspectives around the accessibility, acceptability, and compliance-related challenges of existing treatment to overcome barriers in the future.
• Detailed insights on the unmet need of the existing market so that the upcoming players can strengthen their development and launch strategy.