Guest Column | June 13, 2022

How To Leverage RWE To Facilitate Access To Cell & Gene Therapies

By Youbean Oak, Zachary Kleiman, and Samantha Cambray

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As more and more cell and gene therapies hit the market, the already intense pressure to figure out how to pay for them will only increase. Along with the benefit of one-time administration vs. chronically administered alternatives, these highly innovative treatment options also promise to meaningfully extend life and, in some cases, even cure individuals of disease. However, when they launch, these game-changing therapies carry sticker prices ranging from hundreds of thousands to millions of dollars – without full evidence packages that capture data for all potentially eligible patients or demonstrate lifelong benefit. So, while manufacturers and payers alike genuinely aim to address unmet needs and help individuals live healthier lives, the difficult reality is that these therapies’ price points make them a uniquely “high-risk, high-reward” gamble.

This article shares how real-world evidence (RWE) can be leveraged to help offset economic uncertainties, facilitate access, and create a sustainable foundation for long-term data generation.

Overcoming Clinical Trial Shortcomings

As manufacturers of cell and gene therapies design a clinical development plan, they face several significant hurdles. First, in part since these therapies are technically complex and costly to develop and manufacture, and because of the potential need for specialized administration and post-treatment monitoring, they are extremely expensive. Second, patient recruitment is difficult, given that many one-time therapies treat rare diseases. Third, the first two barriers typically contribute to smaller clinical trial sizes and, ultimately, to a smaller, less varied data pool that may not reflect the broader real-world patient population. So, while the initial data pool may be sufficient for conditional regulatory approval, it likely will lack the broader scope (including sufficient long-term efficacy/safety data) needed for full regulatory approval or reimbursement.

As a result, manufacturers often are required to agree to an up-front conditional marketing authorization and later deliver on post-marketing commitments, which usually involves demonstrating continued safety and/or durability versus the standard of care. Without this complete evidence picture at launch, however, payers are put in a catastrophic reimbursement quandary: how to justify covering high-cost, one-time therapies that may or may not meet projected safety and efficacy measures, especially those that do not fit the typical operating model optimized for lower-cost chronic treatments?

Creating A “Reason To Believe”

Given the numerous significant challenges cell and gene therapies face at launch, manufacturers should consider a flexible, adaptable approach to real-world evidence generation that can help solve for both logistical needs (i.e., post-marketing data commitments to secure full approval) and more strategic needs (i.e., convincing payers to provide reimbursement and facilitate access).

As it relates to fulfilling post-marketing data commitments to secure full regulatory approval, RWE can provide sustainability and flexibility, allowing for an adaptable approach toward generating data against shifting subpopulations and clinical endpoints that regulators or other stakeholders may require or be interested in. More so than clinical trials, patient enrollment criteria and endpoints can be adapted to meet emerging needs from invested stakeholders.

But RWE’s true value may come from a more strategic application – as a critical tool in the negotiation arsenal for cell and gene manufacturers as they seek reimbursement for their high-priced therapies. Innovative access agreements paired with RWE generation can help reduce payer uncertainties associated with available clinical data at launch. Rather than asking payers to take the leap of faith and reimburse a novel one-time therapy, manufacturers can develop and negotiate innovative payment strategies incorporating RWE results. For instance:

  • An installment-based schedule that mimics a traditional chronic therapy payment schedule could be created with contingencies for discounts if the incoming RWE does not support the initial promise of the therapy.
  • A lower up-front price can be initially agreed upon (as an acknowledgement of a cell and gene therapy’s limited data pool at launch), with the potential for future price increases tied to pre-agreed-upon RWE endpoints.
  • Initial coverage/reimbursement strategies could be targeted toward clinical study population characteristics and expanded as more is learned about efficacy in other segments.

This “added security” approach may help convince payers to offer conditional reimbursement and thus enable more patients who suffer from a life-threatening condition to receive therapy when they otherwise may not.

Another approach leverages “pay for performance” models, in which reimbursement is contingent on patients achieving agreed-upon clinical outcomes. A number of cell and gene manufacturers have successfully implemented several of these models described above with payer bodies in the U.S. and EU alike.

Especially strategic and ambitious cell and gene manufacturers may also realize that early and significant investments in RWE can have long-term ROI in the form of reshaping perception and valuation of one-time therapies. As summarized in this article, cell and gene therapies face unique marketplace hurdles and frequent misperceptions of their long-term value. Laying the RWE groundwork early in a product’s life cycle positions not only that therapy, but potentially an entire pipeline of cell and gene therapies for success, as deep and varied data sets across populations materialize and mature over many years following therapy launch. These rich data sets help create a “reason to believe” in the immense value of these unique one-time therapies and support their appropriate estimation by payers and other governing bodies in line with that value.

Considerations For Designing An RWE Strategy

For all the value a strategic RWE approach can provide, deploying one is not necessarily more or less expensive than conducting additional clinical trials.

A biotech company recently compared the cost versus benefit of expanding RWE collection versus conducting additional Phase 3b/4 trials. Analysis concluded the two activities may require similar financial investments. However, an RWE-driven strategy offered more flexibility and broader data access, enabling the manufacturer to retrospectively and prospectively study diverse patient populations, timepoints, and endpoints – all of which would better position them to address payer questions, serve eligible patient populations, and expand into more markets.

With this in mind, manufacturers interested in pursuing a robust RWE strategy should consider the following questions when preparing to bring new cell and gene therapies to market, especially ones in which patient candidates need to urgently receive therapy:

  1. How to architect a holistic RWE strategy that leverages the varied and deep “universe” of potential RWE sources, including access to and incorporation of other registry data at a local, regional, and global scale?
  2. How to scale and plan for the optimal mix of patient types in RWE registry enrollment efforts in order to efficiently achieve the necessary scope to meet regulatory, payer, and clinician needs?
  3. How to design RWE registries to collect a variety of safety, efficacy, and quality of life metrics to allow manufacturers to be agile and flexible in reporting specific endpoints that may be requested by stakeholders?
  4. How to reduce site/patient burden for data collection in order to maximize length of follow-up and thus provide strong long-term data?

In addition to those considerations, manufacturers will need to overcome the well-documented practical challenges of collecting real-world data for the purpose of creating a body of evidence. These include coordinating and supporting infrastructure and registry setup across geographies, consolidating data from disparate sources and systems, and navigating data compliance and governance requirements.

Certainly, implementing innovative RWE strategies carries some challenges, but not doing so very likely carries greater risk than reward. Depending on the disease, therapy, or target patient group, some payers may continue to be hesitant to engage in access agreements irrespective of the promise of RWE generation, and some providers may continue to be reluctant to adopt these new treatment options. On the other hand, given the groundbreaking possibilities one-time therapies offer, others likely will be eager to get in front of the growing pipeline and help create new access frameworks. Plus, the more innovative models that are tried, tested, and implemented, the more evidence will be generated to suggest which work best to meet the needs of all involved stakeholders – all while adding to the reason to believe in the transformative potential of cell and gene therapies.

About the Authors:

Zachary Kleiman, managing consultant in life sciences strategy at Guidehouse, advises biotech and pharma clients on commercial and opportunity assessments, innovative market access strategies, and brand/function value stories. He plays leading roles in Guidehouse’s Cell and Gene Therapy and Oncology Expert Communities.


Samantha Cambray, Ph.D., managing consultant in life sciences strategy at Guidehouse, advises clients on global commercial and market access strategy, including portfolio, launch, and life cycle management planning. She has extensive experience in cell and gene therapies and is a leader of Guidehouse’s Cell and Gene Therapy Expert Community.



Youbean Oak, Ph.D., director in life sciences strategy, leads the Cell and Gene Therapy Expert Community at Guidehouse and specializes in early commercial and market access strategies for innovative cell- and gene-based therapies that have the potential to profoundly impact the existing treatment paradigm.