- The right target → Is the biological mechanism clearly linked to the disease?
- The right patient → Do we know which patients are most likely to benefit, often through biomarkers?
- The right tissue → Can the drug reach the correct tissue or organ at effective levels?
- The right safety → Does the drug have an acceptable safety profile for patients?
- The right commercial potential → Will the therapy meet a real clinical need and gain market adoption?
While the “Rs” are certainly interconnected, biomarkers play a key role in defining both the “right target” and the “right patient.”
The team at AZ published a second article in 2018 reporting that the application of the 5R framework improved success rates from candidate drug nomination to phase III completion “from 4% in 2005-2010 to 19% in 2012-2016.[ii]” There were double digit percentage increases in programs moving to the next phase development as a result of both the “right target” and “right patient” approaches. Separately, Matthew Nelson and colleagues have shown that clinical development programs supported by human genetic evidence are more than twice (2x) as likely to succeed as development programs lacking human genetic evidence[iii], this is an enormous difference.
The value of human genetic support for the “right target” cannot be overstated; however, genetics are not the entire story. While human genetics are an incredibly powerful way to demonstrate the causal role of genes in human disease, genetic data alone can’t monitor response to a treatment or do the practical work needed to get to clinical proof of concept for a new intervention.
A Recipe for Clinical Development Success
However, coupling a target supported by human genetic data with a clinical development strategy supported by biomarker(s) is a recipe for success. If the biomarker can be measured noninvasively and can be easily measured serially in a clinical trial, then clinical proof of concept can be established quickly and often with a relatively small number of trial participants.
The value of these approaches is now being realized, to varying degrees, in at least 3 disease areas:
- Oncology
- Alzheimer’s Disease, and other neurodegenerative diseases
- Rare Diseases
Oncology
The growth in use of circulating tumor DNA (ctDNA) in the context of oncology drug development and clinical care has been truly enormous in recent years and is expected to grow even more; The global liquid biopsy market size is projected to grow from about USD 7 billion in 2025 to about USD 27 billion in 2035.[iv] Examples of use cases abound across nearly all solid tumor types.[v]
Oncology showed the industry that identifying the “right patient” upfront directly increases odds of success and patient benefit.[vi[
- Oncology pioneered liquid biopsy and ctDNA as a tool for monitoring real-time tumor biology[vii]
- Enabled precision eligibility and adaptive trial designs
- e.g., selecting only patients with actionable mutations or subtypes of disease most likely to respond to an intervention
- Enables rational treatment decisions in the setting of minimal residual disease (MRD)
- Reduced screen failures and increased trial success rates
- Demonstrated how biomarkers drive commercial success for targeted therapies
- Set expectations for companion diagnostics and regulatory co-development
Alzheimer’s Disease, and Other Neurodegenerative Diseases
Much like oncology, Alzheimer’s Disease is currently experiencing rapid growth in blood-based biomarkers and clinical diagnostics. Just last year (2025), the first FDA-cleared blood test for Alzheimer’s Disease entered the market.[viii] The global blood-based biomarker for Alzheimer’s disease diagnostics market size is projected to grow by at least several hundred million USD over the next decade from approximately USD 140 million in 2024 to USD 430 million by 2033.ix
Alzheimer’s Disease care is shifting biomarkers from specialized diagnostics to population-level screening that can enable earlier intervention.[x,xi]
- Neurodegenerative disease processes often start 15–20 years before symptoms → need early, scalable detection[xii]
- Blood-based biomarkers (p-Tau 181, Aβ, NfL, GFAP) are moving from research to clinic[xiii,xiv]
- Aiming to replace costly PET scans and invasive lumbar punctures[xv]
- Expands access to primary care, not just specialty neurology centers[xvi]
- Enables earlier and more efficient trial enrollment based on biology rather than symptoms[xvii,xviii]
Rare Diseases
The number and magnitude of challenges in developing drugs for rare diseases is daunting. As the saying goes, the first 3 problems in nearly all clinical trials are (1) enrollment, (2) enrollment, and (3) enrollment. While rare diseases often have incredibly committed patient/family/caregiver communities and foundations, sometimes there may simply not be enough eligible patients in existence to adequately enroll in a traditionally designed clinical trial (i.e. randomized, placebo controlled, one primary outcome etc.), much less have multiple clinical trials running in parallel. In the setting of rare diseases often the availability of biomarker(s) can be the deciding factor in being able to run a clinical trial, at all.
In rare diseases, being able to identify the “right patient” and monitor treatment response can be the difference between a feasible trial and an impossible trial.[xix]
- Rare disease clinical development programs often suffer from both small patient populations andheterogeneous biology
- Biomarker strategies can help:
- Confirm disease or subtype accurately
- Improve patient stratification and trial enrichment
- Detect treatment response when clinical endpoints are slow or variable[xx]
- Serve as surrogate endpoints, supporting accelerated approval pathways[xxi]
- Provide early measures of treatment response that can be monitored on a timescale of days or weeks instead of months or years
Simply Getting a Rare Disease Diagnosis Can Take Many Years
One of the first and sometimes overwhelmingly challenging steps on the path to beginning a treatment (if one exists) is just getting a diagnosis for a rare disease. It has been estimated the average time to diagnosis for many rare disease patients is about 9 years, sometimes up to 30 years![xxii]
In the setting of rare pulmonary diseases, many of the currently available treatments slow or stop progression of disease (but don’t improve function); getting a diagnosis as quickly as possible is of extreme importance for these patients as every day they are literally losing time. One such example is Lymphangioleiomyomatosis or LAM, a rare lung disease that affects women (almost exclusively). LAM patients experience abnormal growth of smooth muscle cells, especially in the lungs, which leads to loss of lung function, and accumulation of lymph rich fluid in the chest and abdomen.[xxiii] Fortunately, a randomized, double-blind comparison of sirolimus with placebo showed that sirolimus does indeed stabilize lung function, reduce serum VEGF-D levels (a useful biomarker in LAM patients), and was associated with a reduction in symptoms and improvement in quality of life.[xxiv] However, even with a safe and effective drug available, getting a diagnosis of LAM can still be an extraordinary challenge, with some women still taking many years to get a diagnosis; which can mean delaying the start of a drug and losing lung function for years of time.
Conclusions
- The value of biomarkers in the development of new treatments, detection of disease, monitoring of treatment response, and monitoring of disease activity will only increase in the future.
- This value can be seen having an impact nowin oncology, neuroscience, and rare diseases.
- Blood-based (and other noninvasive approaches) biomarkers can revolutionize and rapidly accelerate a patient’s time to diagnosis across many diseases due to their ability to facilitate patient access to diagnostic testing around the world.
Robert Lavieri, PhD, is an operational and scientific leader with two decades of global experience spanning human genetics, translational medicine, and clinical R&D across small, medium, and large organizations. He serves as the VP of Business Development and Translational Medicine at TrilliumBiO and is passionate about advancing translational medicine and building meaningful partnerships that drive innovation and impact across the life sciences industry.
References
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