For early-stage pharmaceutical companies, regulatory approval is a major milestone, as fewer than 1% of drugs entering human clinical trials ultimately reach the market (1). However, approval alone does not guarantee that a medicine will be prescribed, reimbursed, or adopted by patients. According to Trinity Life Sciences, half of US pharmaceutical launches in 2023 failed to meet their first-year forecasts, highlighting the challenges of translating scientific promise into commercial success. (2)

Biogen’s Aduhelm (aducanumab) illustrates what happens when a product fails to consider the needs of different stakeholders. The FDA granted it accelerated approval for Alzheimer’s disease in 2021, based on reduced amyloid plaques as a surrogate endpoint. Many clinicians questioned whether the clinical benefit had been demonstrated, and payers and policymakers questioned whether an initial price of $56,000 per year was justified. In 2022, the US Centers for Medicare & Medicaid Services limited coverage to patients participating in clinical trials, and Biogen withdrew its European marketing application after the EMA signaled the data were insufficient. Biogen announced in 2024 that it would discontinue the product. (3,4)

Demonstrating safety and efficacy is essential, but medicines must also deliver clear, measurable value to patients, healthcare professionals, and payers.

Developing a strong value proposition should begin early in the development process. 

Evidence gathered for regulatory approval often fails to address the clinical, practical, and economic questions that drive reimbursement and adoption (5). Engaging stakeholders before key development decisions helps companies identify unmet needs, refine strategies, and generate evidence that supports both regulatory and commercial goals.

What defines an early asset value proposition?

A value proposition is a clear, evidence-based statement that explains why a pharmaceutical asset is important to those who develop, fund, prescribe, or use it, and how it may offer advantages over current options.

For early-stage assets, it is a hypothesis regarding future value in terms of real-world outcomes, such as improved symptom control, fewer side effects, greater convenience, or reduced healthcare demands. (6)

It is also different from a target product profile (TPP). A TPP outlines the product’s desired characteristics, such as indication, efficacy, safety, and dosing, whereas the value proposition explains why these characteristics matter to stakeholders and the evidence supporting their relevance. (7)

Developing a value proposition early on does not mean setting a launch price or claiming clinical benefit before evidence exists. Instead, it involves identifying the assumptions that could affect future adoption and testing them as new data become available. These insights help guide decisions on target populations, clinical endpoints, and comparators.

Understanding the stakeholders

Medicines often have multiple value propositions. Different stakeholders use their own criteria to assess potential, and their priorities may not always align. Understanding these perspectives helps companies identify the most important benefits and determine the evidence needed to support adoption. 

Patients: Why use it?

Patients seek treatments that improve the outcomes most relevant to their daily lives, such as fewer symptoms, better sleep or minimised disruption to routines. Treatment burden is also a key consideration: dosing frequency, side effects, monitoring for safety or treatment response (such as regular blood tests or clinic visits), and ease of administration all influence whether a medicine fits into patients’ lives. 

Interviews, focus groups, patient-journey mapping, and patient-reported outcome measures help identify unmet needs and acceptable trade-offs. These insights inform treatment design and clinical endpoints, ensuring development focuses on outcomes that patients genuinely value. Patient research clarifies what matters to people, while clinical studies demonstrate what the treatment achieves.

Policymakers: Why fund it?

Policymakers assess how a treatment supports broader health priorities, including improving population health, reducing inequalities, and strengthening healthcare system capacity. Medicines that address significant unmet needs or improve outcomes for underserved groups can help achieve these goals. 

National health strategies, epidemiological research and discussions with policy experts help companies understand these priorities. However, anticipated benefits, such as fewer hospital admissions, must be supported by evidence rather than assumed from a treatment’s mechanism of action.

Regulators: Why approve it?

Regulators such as the Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) evaluate whether the evidence supports a favourable benefit-risk balance for a proposed indication. Their decisions are separate from pricing, reimbursement or commercial value. 

Early scientific advice can help companies clarify acceptable endpoints, study designs and evidence requirements. Opportunities to align regulatory and health technology assessment (HTA) needs are particularly valuable: a 2016 EMA review of 31 parallel scientific advice procedures found that in approximately 70% of cases, one trial design or development programme could satisfy the evidence needs of both regulators and HTA bodies (8,9). This shows the potential to design development programmes that meet both sets of requirements.

Providers and healthcare professionals: Why prescribe it, and to whom?

Clinicians need clear reasons to prescribe a new treatment rather than an established treatment. They consider comparative efficacy, safety, suitability for different patient groups, and practical factors such as administration, monitoring, and impact on workload. Interviews, surveys, and advisory boards can identify which attributes would influence prescribing decisions. 

Testing a hypothetical TPP with clinicians can clarify which patients would benefit most, what would justify a change in practice, and which clinical outcomes would be most persuasive.

Payers: Why pay for it?

Payers assess whether the additional benefits of a medicine justify its cost within limited healthcare budgets, evaluating clinical effectiveness, cost-effectiveness, affordability, and added value relative to alternatives. 

Bluebird bio’s Zynteglo, a one-time gene therapy for beta-thalassaemia, illustrates the challenge of demonstrating value when the cost is paid upfront, but the benefits unfold over many years. Priced at around $1.8 million in Europe, it asked payers to commit a large sum now for benefits, such as freedom from regular blood transfusions, that could only be confirmed over time. Uncertainty over long-term durability and reimbursement can complicate access to high-cost therapies. (10,11)

Early review of HTA decisions, consultation with payer experts, and health-economic modelling help companies identify relevant comparators and appropriate endpoints. It is also worth remembering that cost-effectiveness and affordability are not the same: a treatment may offer good value per patient but still have significant budget implications if many people are eligible. (12)

Competitors: What differentiates it?

A medicine’s value depends on how it compares with available alternatives. Even strong clinical results may not lead to meaningful differentiation if another treatment offers similar outcomes with fewer side effects, simpler administration, or lower cost. 

Desk research using clinical trial registries, scientific publications, treatment guidelines, and pipeline databases helps companies map current and emerging competitors. The goal is to identify benefits that matter to stakeholders and could differentiate the asset when it reaches the market. Comparisons should be made carefully, since differences between clinical trials alone do not establish that one treatment is superior to another.

Turning stakeholder insights into action

Understanding stakeholder perspectives is only the first step. Impact comes from applying these insights to guide development decisions. A practical approach involves four stages:

1. Map the landscape. Identify the unmet need, existing standards of care, emerging competitors, and key stakeholders who influence adoption.

2. Gather stakeholder insights. Use interviews, focus groups, surveys, advisory boards, and regulatory or HTA engagement to explore what matters most to each group.

3. Prioritise value drivers. Identify which benefits matter most, where stakeholder priorities conflict, and which uncertainties pose the greatest risk to adoption. Not every preference needs to become a clinical endpoint. The goal is to understand which evidence will support meaningful decisions.

4. Test and refine. Apply the findings to the development and evidence-generation plan, and revisit assumptions as new clinical data emerge and the competitive landscape evolves.

Organon’s experience with NICE Advice illustrates this approach. While planning market access for an obstetric product, the company engaged with NHS stakeholders, including clinicians and NHS Supply Chain representatives. These discussions helped Organon better understand the UK healthcare environment and the importance of real-world evidence. It then worked with Health Innovation North East and North Cumbria to establish real-world evidence collection sites within NHS trusts (13). 

This example illustrates how early engagement can guide evidence generation and support market access planning. It does not guarantee success, but it helps companies identify evidence needs before development decisions become costly to change.

Building value into development from the start

An asset’s value proposition should evolve as the evidence base grows. Engaging stakeholders early, understanding the competitive landscape and testing assumptions throughout development help companies make informed decisions about what to develop, which patients to prioritise and which evidence to generate.

Regulatory approval is essential, but it is only one step. The real challenge is developing medicines that deliver meaningful value to patients, healthcare professionals and payers.

References

1. Citeline. Pharma R&D Annual Review 2026. https://www.citeline.com/en/rd26

2. Trinity Life Sciences. Moving the Needle: Lessons from the 2023 Launch Class. 2024. https://trinitylifesciences.com/resources/moving-the-needle-lessons-from-the-2023-launch-class/

3. Climan A. The Aducanumab Controversy: Accelerated FDA Approval Leads to Agency Distrust. 19 July, 2024, Neurology Advisor

4. EMA.Withdrawal of application for the marketing authorisation of Aduhelm (aducanumab), 22 April, 2022. https://www.ema.europa.eu/en/documents/medicine-qa/questions-and-answers-withdrawal-application-marketing-authorisation-aduhelm-aducanumab_en.pdf 

5. Ramagopalan SV, Bacon C, Walker M, Ryan ML. The need to consider market access for pharmaceutical investment decisions: a primer. J Comp Eff Res. 2025 May;14(5):e250036. doi:10.57264/cer-2025-0036

6. Parexel. Focusing on value drivers to reduce risk in early-stage drug development. https://www.parexel.com/insights/blog/focusing-on-value-drivers-to-reduce-risk-in-early-stage-drug-development

7. Boccardi M, Gold M, Mahant V, Marincola FM, Gunn A. Why should academia care about the Target Product Profile? J Transl Med. 2024 Aug 2;22(1):716. doi:10.1186/s12967-024-05520-0 PubMed PMID: 39095839; PubMed Central PMCID: PMC11295361.

8. Tafuri G, Pagnini M, Moseley J, Massari M, Petavy F, Behring A, et al. How aligned are the perspectives of EU regulators and HTA bodies? A comparative analysis of regulatory‐HTA parallel scientific advice. Brit J Clinical Pharma. 2016 Oct;82(4):965–73. doi:10.1111/bcp.13023

9. EMA. Early dialogue with regulators and HTA bodies. 31 March, 2016. https://www.ema.europa.eu/en/news/early-dialogue-regulators-hta-bodies 

10. J LaMattina. What Bluebird Bio Gets Wrong In Pricing For Its $1.8 Million Drug. 19 July, 2019. https://www.forbes.com/sites/johnlamattina/2019/06/19/what-bluebird-bio-gets-wrong-in-pricing-for-its-1-8-million-drug/ 

11. A Feuerstein. Patients with rare blood disorder benefit from Bluebird gene therapy while denied access in Europe. 11 December, 2011. https://www.statnews.com/2021/12/11/patients-with-beta-thalassemia-benefit-from-bluebird-gene-therapy-while-denied-access-in-europe/ 

12. National Institute for Health and Care Excellence. Guide to the processes of technology appraisal [Internet]. London: NICE; 2014 [updated 2018 May 30]. Process and methods guide; no. PMG19. Available from: https://www.nice.org.uk/process/pmg19. 

13. NICE. Market access planning with Organon: A NICE Advice case study. https://case-studies.nice.org.uk/organon/index.html