Key takeaways
- Unmet need: Diagnosis is often delayed, and few disease-modifying therapies exist, offering only modest benefits or limited applicability to ALS patients.
- Burden of disease: ALS leads to a loss of about 13 QALYs per person and imposes high costs, with annual healthcare spending of $178 million in the UK and $2.5 billion in the US – figures that triple when societal costs are included.
- Commercial value: A successful ALS treatment could generate $26 – $40 billion in the US, $1.7 billion in the UK, and $1.1 – 4.0 billion in other countries over 10 years; complete eradication could deliver up to $143 billion in value across seven countries studied.
- Key insights and implications: New treatments for ALS represent major potential value and commercial opportunity, but current HTA frameworks often undervalue such advances, especially when wider societal costs are not fully considered.
- Opportunities for strategic investment: Rapid growth in ALS research, advances in AI and gene therapy, orphan drug incentives, and limited competition create strong potential for high-value investment and innovation in ALS therapies.
Amyotrophic lateral sclerosis (ALS) is a rare, rapidly progressive neurodegenerative disease with devastating clinical and economic consequences. Despite its relatively low prevalence, ALS imposes a disproportionate burden on patients, caregivers, and healthcare systems due to its complex diagnosis, limited treatment options, and high resource utilisation. This report presents a comprehensive commercial case for investing in ALS research and therapeutic development, highlighting the unmet need, socioeconomic burden, and market opportunity across seven major countries: the UK, US, Canada, France, Germany, Italy, and Australia.
Unmet Need and Diagnostic Challenges
ALS is characterised by motor neuron degeneration, leading to muscle atrophy, paralysis, and death, typically within 2-5 years of symptom onset. Diagnosis is often delayed by 10-16 months from symptom onset due to symptom heterogeneity and the absence of reliable biomarkers (Richards, Morren and Pioro, 2020). Only three disease-modifying therapies (DMTs) have been approved to date, each offering modest benefits. The lack of effective treatments and validated biomarkers emphasises the urgent need for innovation in diagnostics and therapeutics.
Opportunities for Strategic Investment
Despite these challenges, ALS research is at a pivotal moment. Key enablers include:
- Rising public and private funding: NIH funding for ALS increased nearly fivefold from 2015 to 2024.
- Use of large-scale datasets: Initiatives like the Global Neurodegeneration Proteomics Consortium support biomarker discovery and provide insights to novel target discoveries.
- Cross-disease potential: Genetic, pathological, and clinical overlap with frontotemporal dementia (FTD) and other neurodegenerative diseases suggests broader therapeutic applicability.
- Platform trials: Adaptive designs like the HEALY ALS and EXPERTS Platform Trials are streamlining drug development.
- AI and in-silico technologies: These tools reduce preclinical costs and accelerate unlocking disease understanding and novel target and biomarker identification and speed up drug discovery and development.
These developments position ALS as a high-impact area for both scientific advancement and commercial return.
Burden of Disease: Socioeconomic and Healthcare Resource Impact
The burden of ALS is particularly stark when expressed in terms of quality-adjusted life years (QALYs) lost. In the UK, an individual diagnosed with ALS may lose approximately 12.6 QALYs over their lifetime, equating to a monetised health loss of $1.2 million per patient. At the population level – given that there are 5,000 prevalent ALS cases in the UK – this translates to $5.9 billion in lost health value across existing patients’ lifetimes. Similar estimates across other countries reveal a total monetised health burden ranging from $1.1 billion in Australia to $34.2 billion in the US, even before accounting for healthcare and broader societal costs.
Furthermore, ALS patients require intensive, multidisciplinary care, with yearly per-patient healthcare costs ranging from $23,039 in Canada to $76,823 in the US. When extrapolated to national populations, these costs represent a significant strain on healthcare systems, reaching $2.5 billion annually in the US alone.
Beyond direct medical costs, ALS imposes substantial non-medical and indirect costs which, when taken into account, approximately triple the cost estimates above. This is because informal caregiving, home modifications, and productivity losses account for up to 64% of the total cost burden, as evidenced by studies in Germany and Canada.
Quantifying the Commercial Opportunity
The report employs three complementary approaches to estimate the commercial value of a successful ALS treatment, the results of which can be compared with the likely investment required to bring such therapies to market:
Approach 1 – Socioeconomic Burden
Monetising the total burden of ALS per year, including QALY losses and healthcare costs (but excluding broader societal costs) of the prevalent population, revealed an upper-bound one-year value of:
- $34.2 billion in the US
- $6.1 billion in the UK
- $1.6-4.4 billion in other markets
Approach 2 – Proxy Pricing via tofersen
Our second approach used the price of tofersen as a benchmark and scaled this price to the full ALS population. We considered this to be a reasonable benchmark, as a recently approved innovative therapy for a genetic form of ALS. We found yearly commercial values of:
- $4.8 billion in the US
- $209 million in the UK
- $139-$347 million in other countries
These values increase substantially over time as incident cases are added, with the US market alone reaching $39.9 billion in cumulative value by year ten.
Approach 3 – Conventional HTA Modelling
A Markov model adapted from Tappenden et al. (2024) evaluated three hypothetical treatment scenarios. Only the most effective scenario, halting disease progression, produced consistently positive value across all countries. We found the yearly value of this hypothetical treatment to be:
- $3.14 billion in the US
- $203 million in the UK
- $137-$3493 million in other countries
Less effective treatments were often deemed not cost-effective, even at price zero, highlighting limitations in current Health Technology Assessment (HTA) frameworks for rare, high-burden diseases, such as ALS.
Spillover Effects and Broader Value
Given the genetic, pathological, and clinical overlap between ALS and Frontotemporal Dementia (FTD), we estimate that a dual-indication therapy could expand the addressable market by up to 2.5-fold. In the US, this would increase the yearly commercial value from $4.8 billion to $12.4 billion. Additionally, broader societal costs, including informal caregiving and productivity losses, are substantial but often excluded from HTA evaluations. Incorporating these could further strengthen the economic rationale for ALS investment.
Conclusion
ALS presents a compelling case for strategic investment. The convergence of unmet medical need, advancing research capabilities, and demonstrable commercial opportunity creates a promising environment for innovation. While current HTA methods may undervalue ALS treatments, alternative frameworks that account for severity, rarity, and societal impact are essential to unlock the full value of therapeutic advances. This report demonstrates that a successful ALS treatment would not only transform patient outcomes but also deliver significant economic and societal returns.
This Grant Funded Research Report was commissioned and funded by the Challenge Works as part of the Longitude Prize on ALS.