One of the greatest challenges in the early stages of asset development is the data and evidence gap; development teams’ foundation of known clinical outcomes in a fixed treatment landscape. As teams make crucial decisions on when and how to take an asset forward, they have to rely on assessments of the current situation and predictions of what the future landscape may look like in five-to-10 years, to determine the potential value of a new asset to patients, physicians, and payers.
Given the current evolving environment, it is likely that both the treatment paradigm and reimbursement landscape will have shifted by the time of launch. Physicians, patients, payers, and regulators will all be looking for different pieces of information to justify the role and value of a new therapy, particularly as that space inevitably becomes more crowded. Teams developing assets for conditions with only one or two approved therapies today are likely to face an environment with seven or eight approved medications in 2021, which presents an altogether more competitive reimbursement challenge. Thus, teams need to consider how to demonstrate an asset’s value to all key stakeholders clearly and supported with evidence.
The challenge in making these decisions about the future is the data gap; with phase 3 data years away, the constantly evolving landscape and shifting reimbursement requirements, how can development teams determine the future value of an asset?
Answering that question requires evaluation of three distinct sources of value: clinical, patient and commercial. Though some consider these value streams independently, the only way to understand how they interact with, and amplify, each other is to review them collectively.
From a clinical perspective, value for early-phase assets is based on a combination of scientific feasibility and medical relevance: is there a solid rationale to believe that the asset will work in a given disease state? Mapping out this current and potential future positioning requires deep therapeutic area knowledge, willingness to look at all the evidence (positive, negative and neutral), and an understanding of what value means to clinicians and patients.
In the absence of large phase 3 datasets, feasibility can only be evaluated based on the mechanisms and pathways being targeted, which populations are most likely to benefit, and how this benefit can (or should) be evaluated in a clinical setting. Understanding the medical relevance of the condition and population to be treated is also fundamental: is it an already-defined segment, or will you need to work with physicians and regulators to define this population in a way that delineates a compelling rationale for a new treatment?
In a perfect world, all key stakeholders (physicians, payers/regulators and patients) want an easy-to-measure biomarker that correlates with response to your asset in a clearly-defined population, as is the case for HER2 and trastuzumab response in breast cancer. However, in this example, HER2 is really a target of trastuzumab and not merely a marker. More often, the relationship between biomarkers and findings on imaging or other measures does not show a strong, clear relationship with treatment outcomes. Where a new asset is targeting novel pathways, or a rare disease with little information on markers of disease progression, it may be necessary to establish and validate appropriate surrogate markers of response.
The ‘patient’ source of value flows from this ‘clinical’ value. The goal of any therapy, whether disease modifying or symptom management, is to meaningfully improve patients’ lives and alleviate the burden of their condition. In the modern healthcare landscape, the voice of the patient is emerging as a powerful driver of value for new agents, particularly in understanding the various ways in which new treatments can offer benefits beyond the standard outcomes. Therapies that are not disease-modifying but alleviate debilitating symptoms may offer considerable value to the patient, and yet this value may not be reflected in outcome measures of disease progression. As a result, payers and regulators are becoming more and more responsive to patient needs when considering access and indications.
Fully integrating clinical and economic value is an important part of assessing the third source of an early asset’s future value – the commercial aspect. Their future commercial viability has to be considered in the context of their revenue potential, future market position and increasingly complex access schemes. While we all dream of bringing an asset to market that offers transformative benefits to patients and rapidly achieves first-line status, the vast majority provide some degree of incremental clinical benefit and require careful positioning for an appropriate place in therapy.
Optimising the outcome of this process requires scenario-based evaluations of potential future treatment landscapes, and mapping of how both small and large changes may influence evolving reimbursement and access paradigms. This kind of scenario-based approach is central to understanding if it is realistic for a novel therapy to achieve first-line status in a broad population versus third-line status in a clearly articulated subpopulation – and growth potential may vary dramatically based on the ability to firmly establish differentiation against competitors, not just from an efficacy/safety perspective, but from a value perspective as well.
These three sources of value – clinical, patient and commercial – need to be considered collectively. Rather than evaluating each independently via different teams, the optimal path is a collaborative approach that incorporates a multidisciplinary team to evaluate, assess and prioritise assets and development pathways. This helps teams reach key decisions faster and more efficiently and, importantly, with endorsement from all stakeholders.
Understanding the concept of value, and where that value will manifest itself, is central to good decision making in early asset development and commercialisation. If each source is evaluated in isolation, teams can miss opportunities where incremental value in each of the clinical, patient, and commercial arenas can become greater than the sum of their parts.