The $17 Billion Race: Why New Treatments for Alzheimer’s Disease Are Changing the Game

The fight against Alzheimer’s disease (AD) is entering a new, highly competitive phase, driven by recent scientific breakthroughs and a growing global market. While therapies targeting amyloid proteins have recently been validated, there remains a critical and ongoing unmet need for drugs that utilize alternative mechanisms of action. Experts are encouraged to see a broader range of therapeutic options emerging in the pipeline for patients. This expanding innovation is mirrored by massive financial growth expectations: according to GlobalData analysis, the Alzheimer’s disease market is expected to experience a high compound annual growth rate (CAGR) of 21.8%. This means the market, which stood at $2.4 billion in 2023, is forecasted to swell to an impressive $17 billion by 2033 across the eight major markets (8MM: the US, France, Germany, Italy, Spain, the UK, Japan, and China).

The Reign of Amyloid Targets and the Race for Convenience

Pharmaceutical giants Eli Lilly, along with Biogen and Eisai, currently hold significant sway over the Alzheimer's disease market. Their success is attributed to the approvals of their respective therapies: Kisunla (donanemab) from Eli Lilly, approved in 2024, and Leqembi (lecanemab) from Biogen/Eisai, approved in 2023. Both of these approved therapies specifically target amyloid. Disease-modifying therapies (DMTs), such as these amyloid-targeting drugs, are anticipated to dominate the global AD market, contributing 69.2% of the total market share by 2033, with drugs aimed at amyloid beta (Aβ) making up the majority of this segment. By 2033, GlobalData forecasts that Leqembi could generate approximately $2.9 billion in global sales, while Kisunla could reach around $2.3 billion.

However, the focus on amyloid treatments is not without its risks. There are safety concerns associated with these therapies, specifically amyloid-related imaging abnormalities (ARIA). This existing concern heightens the urgency for developing alternative treatment approaches.

Eli Lilly, seeking to capitalize on the success of Kisunla, is developing a second amyloid-targeting drug called remternetug. Remternetug is a monoclonal antibody (mAb) designed to target N3pG beta-amyloid, which is also known as amyloid precursor protein (APP). Its mechanism involves binding to and clearing deposited amyloid plaques, aiming to halt the pathological cascade linked to Alzheimer’s disease. In a Phase II trial, remternetug achieved "rapid and robust" amyloid plaque clearance. However, the Phase II data also showed 10 cases of ARIA among 41 patients, although only 24 of these patients received the study drug. Just one of these ARIA cases was symptomatic and resolved after the study drug was stopped and oral steroids were administered.

The Phase III TRAILRUNNER-ALZ 1 trial (NCT05463731) for remternetug is currently enrolling patients, with 600 initially scheduled to receive the drug or a placebo during the double-blind phase. An additional 974 patients with early Alzheimer's disease will be enrolled in an addendum safety cohort, receiving open-label remternetug. This study is expected to finish in March 2026.

A major strategic advantage for Eli Lilly’s remternetug lies in its planned method of administration. While the drug can be given via intravenous infusion, it is also being investigated for subcutaneous injection. Dr. Joy Snider, Professor in the Department of Neurology at Washington University School of Medicine, notes that the drug can be thought of as the "son of Kisunla". Snider explains that the key benefit is the subcutaneous formulation, which represents a significant step forward for these types of drugs. Erela Dana, Director of Neurology and Immunology at GlobalData, agrees, stating that the subcutaneous formulation could address key access barriers associated with the intravenous (IV) infusions that historically complicated anti-amyloid therapies. This is particularly important since Lilly’s main competitor, Biogen and Eisai’s Leqembi, recently gained approval for a subcutaneous version of their therapy for maintenance dosing, and is working toward subcutaneous indication for initiation. Dana notes that for Lilly’s remternetug to succeed, it must be at least as effective as Kisunla and Leqembi, if not more so, in this increasingly competitive environment. GlobalData forecasts remternetug as a promising pipeline product, projecting peak sales of $901.2 million in 2031. However, Dana cautions that this assessment is "tempered by limited available clinical data" and the inherent risks associated with the anti-amyloid approach, specifically ARIAs.

Exploring Triple-Targeting and Novel Mechanisms

Given the safety profile and mechanism limitations of anti-amyloid therapies, there is strong interest in drugs that utilize non-amyloid pathways.

Annovis Bio is pursuing a drug called buntanetap tartrate, which is being investigated in a Phase III Alzheimer’s disease trial (NCT06709014). Buntanetap is unique because it offers a triple-pathway approach, simultaneously inhibiting the synthesis of amyloid-beta, tau, and alpha-synuclein. This design potentially allows the drug to address multiple neurodegenerative mechanisms at once. Furthermore, Dr. Snider finds it exciting that the drug is an oral formulation, which is a major advantage.

However, Snider notes that the drug has been around for some time and, in earlier iterations, failed to meet efficacy endpoints, reducing her overall enthusiasm. Mixed data resulted from a Phase II/III trial where the study endpoint was not met, causing the company’s stock to drop. Though the biotech tried to reassure investors by highlighting that the therapy led to a significantly higher rate of improvement on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11) compared to a placebo in the trial. The current Phase III trial is investigating the once-daily oral drug in an estimated 760 patients with early Alzheimer’s disease, with evaluations scheduled at six months and 18 months. The primary trial completion is set for December 2027.

Erela Dana praises buntanetap for its innovative dual trial design, which allows the evaluation of both symptomatic and disease-modifying effects, potentially accelerating regulatory approval. Its oral administration and absence of ARIA side effects associated with monoclonal antibodies position it as a potentially more accessible treatment option. Nevertheless, Dana points out a key commercial challenge: as a smaller biotech, Annovis Bio may struggle with commercialization and would likely require a major partnership to compete effectively against established players like Eisai/Biogen and Lilly. GlobalData predicts a global sales forecast for buntanetap of $797 million in 2033.

The Convenience and Promise of Oral Disease Modification

Another promising drug in the pipeline is AriBio’s AR-1001, which is being studied in the Phase III POLARIS-AD trial (NCT05531526) in patients with early Alzheimer’s disease. This drug is an oral phosphodiesterase 5 (PDE5) inhibitor, representing yet another different mechanism of action that has garnered interest in the scientific community.

In a previous Phase II trial (NCT03625622), the once-daily 30mg oral PDE5 inhibitor demonstrated a statistically significant improvement in plasma pTau-181 levels compared to placebo after 26 weeks, and across both the 10mg and 30mg cohorts after 52 weeks. Patients initially on placebo but later assigned to treatment also showed statistically significant improvements at the 52-week point. Crucially, the Phase II study reported no cases of ARIA.

Jae-young Ha, Senior Vice President of AriBio, stated that the 30mg dose was chosen for the Phase III trial based on the Phase II data. Ha notes that patients treated with the higher dose, particularly those with higher baseline pTau-181 levels, showed consistent improvement trends in both cognitive performance and daily living abilities compared to placebo. Ha interprets these results as providing "robust clinical proof of concept" and underscoring the drug's potential as a disease-modifying therapy. While Dr. Snider acknowledges that the drug met some, though not all, endpoints in Phase II, she emphasizes the need to wait for Phase III data, noting that successful Phase II results do not always translate to Phase III success.

The Phase III trial’s primary endpoint focuses on the change in Clinical Dementia Rating – Sum of Boxes (CDR-SB) and will evaluate patients for 52 weeks, with an optional 52-week extension. Secondary endpoints include assessments of daily living (A-iADL), cognitive ability (ADAS-Cog 13, MMSE), mood (GDS), and changes in plasma and cerebrospinal fluid (CSF) biomarkers. Topline results are anticipated near the end of Q2 2026.

AR-1001 scores highly in GlobalData's competitive assessment due to its novel mechanism of action and the convenience of oral dosing. Dana observes that this profile positions it as an attractive alternative to the current generation of complex anti-amyloid infusion therapies. The convenience of oral administration is highly valued; as Alzheimer's is a chronic condition requiring long-term treatment, oral dosing is considered essential. Furthermore, Ha points out a major practical benefit: oral administration once a day offers a price advantage over monoclonal antibody biologics, which often require a one-hour infusion at a hospital every two to four weeks. Similar to Annovis Bio, AriBio is actively seeking major licensing partnerships to overcome the commercial limitations associated with being a smaller biotech company. GlobalData predicts AR-1001 could reach a global sales forecast of $674 million in 2033.

Alzheimer’s Researchers:

Goldie S. Byrd

Dr. Goldie S. Byrd is the director of the Maya Angelou Center for Health Equity and a professor of social sciences and health policy at Wake Forest University School of Medicine. Her research focuses on the genetics of Alzheimer's disease in African Americans, who are disproportionately affected by the disease. Byrd's work also focuses on ensuring health equity by increasing the representation of minority populations in clinical research and trials. She founded the Center for Outreach and Alzheimer's Aging and Community Health (COAACH) to engage and support underserved communities. 

Clara Li

Dr. Clara Li is a clinical neuropsychologist and associate professor at the Icahn School of Medicine at Mount Sinai. Her research focuses on improving the diagnosis and treatment of Alzheimer's and related dementias, particularly within Asian American communities, which are often underrepresented in research. To address this disparity, Li has led projects to develop linguistically and culturally adapted assessment tools for older adults who speak Chinese, with plans to extend her work to other Asian languages.