The stakes are high for cell and gene therapy manufacturers. The nature of these treatments, and their use of living human cells or genetic material, creates new intricacies and dependencies that disrupt the traditional commercialization process. The new commercialization process for these therapies is interconnected and personalized, requiring a higher degree of integration between specialized logistics, patient programs, and health outcomes evidence – making data a strong connective thread that helps weave together the value story for these products.
Stakeholders, ranging from regulatory bodies to payers to prescribers and even to patients, will review the data generated during a cell or gene therapy clinical trial with more scrutiny than ever before. And, each stakeholder will have its own set of priorities and metrics by which it will judge the therapy. While this dynamic is not entirely new, the challenges for a manufacturer to provide this data – and the consequences that may arise without it – are. The decisions a manufacturer makes in clinical trial design and reporting will have greater implications for the commercial supply chain compared to traditional products.
To design a clinical trial that will deliver all of the data complexities ultimately required of a cell or gene therapy, a manufacturer must start with the end in mind – when the therapy is approved, covered, and available to patients. Trial designers must think about each stakeholder along the supply chain individually and collectively to understand the qualitative and quantitative measures each will need to appreciate the value of the therapy.
Ideally, the manufacturer should create a multi-disciplinary advisory group, made up of providers, payers, distributors and patients, which can offer guidance and perspective throughout the therapy’s life cycle. Their perspectives can be informed by early discussions with regulator’s agencies as well. For example, I have been on advisory boards where the preferred trial design for regulatory bodies differed substantially from the design preferred by healthcare decision makers. There will be times when stakeholder needs converge and diverge, so understanding their needs as early as possible in the development process will aid in the development of an effective data strategy to address the evidentiary gaps.
Two to three years pre-launch, manufacturers should go directly to relevant regulatory agencies to gain insight into their requirements and review the current marketplace to understand the data needed to support their therapy. Certainly, regulators are going to be interested in cure rate, failure rate, adverse events, and other anticipated data; however, they are also going to be particularly interested in the comparator that is selected for the study. More than 30 percent of cell and gene therapies target rare diseases associated with small and often widespread patient populations. Meaning, researchers will need to recruit patients from diverse geographic regions, and in each region, there could be a different established standard of care. Therefore, manufacturers will need to carefully consider and understand the treatment landscape in the geographies from which they pool patients to fill their trials.
Evaluating a commercialization partner
Fortunately, there is significant information available to help manufacturers educate themselves on these market nuances. Evaluating commercialization partners with expertise that ranges from a global to hyper-local understanding of care and requirements can help this process. Together, manufacturers and their partners can review the data, looking first for overlaps (e.g., evaluating which countries have the same standards of care and provide a comparator that is relevant to multiple regulatory bodies).
If, however, there is not significant overlap, a partner can help a manufacturer identify which country may be the best in which to launch its innovative product, providing it with an opportunity to obtain additional evidence for future markets. In addition, a partner can help identify what data is available from other clinical trials to possibly serve as an indirect comparator, allowing the manufacturer to benefit from not only its own data but also the research that has been done previously or is being done simultaneously.
As noted earlier, regulatory bodies aren’t the only stakeholders that need to be considered during the design of a cell or gene therapy clinical trial. Payers play a critical role in creating access to a manufacturer’s product. They, too, must be considered early in development – at least prior to Phase III. Not only would it be devastating to patients eagerly awaiting the promise of a cell or gene therapy but also it’s extremely costly for a manufacturer to successfully navigate regulation, receive approval, and then not receive coverage for the therapy.
Much like the approach to regulators, manufacturers should invite payers to join in their processes. It’s important to understand how insurers will view a particular therapy – is this gene therapy likely a first line treatment or a third or fourth option? The trial data may show that the therapy had even higher efficacy rates in a sub-population within the cohort. This will influence how a payer interprets the value of the therapy and how it considers different coverage models.
Payers will look not only for the data relevant to regulators but also associated costs. For example, what is the cost of an adverse event while on a new therapy? And, how does that differ from the standard of care? It is important that a manufacturer’s data strategy capture resource utilization while on its therapy and the comparator or accepted standard of care to answer key questions. Are there “hidden” costs associated with the current standard of care that are eliminated by the new therapy? Does current practice create a side effect that must be managed and, therefore, has a cost to both the patient and the payer?
Of course, not all questions will be answered immediately. Commercial and private payers are also struggling to balance the burden of paying the upfront cost of the therapy with ensuring a long-term economic benefit to offset the initial investment. Significant research being done to better understand patient movement across healthcare plans and how that could potentially impact cell and gene therapy models moving forward. In the meantime, manufacturers must work with partners to understand payer concerns and to create the most compelling value story possible.
Beyond clinical trials
Once approvals and coverage are granted, manufacturers must contend with the level of uncertainty in real-world results, which is particularly high for cell and gene therapies. This uncertainty could strongly affect stakeholder confidence in cell and gene therapy use, which in turn, affects both the product’s success and ability to help patients. As we have seen with many specialty products in the past, approval does not always equate to adoption. Provider and patient education will be a large and critical component of any commercialization strategy for cell or gene therapies, and that education can be bolstered significantly by data. The right mix of data can help stakeholders gain confidence and mitigate concerns regarding efficacy as well as comparative effectiveness, adverse events and the impacts to the patient.
Therefore, the need for data does not end with the conclusion of a clinical trial. Cell and gene therapies have a level of interconnectivity between manufacturing, logistics, patient support, and reimbursement rarely seen in health care. As a result, cell and gene therapies will need – in some ways like many other products – constant, ongoing data collection, interpretation, and distribution. Manufacturers will need to build or – more likely and more effectively – enlist partners who can build integrated data sets that provide not only the therapy owner, but all stakeholders “needle-to-needle” visibility.
Ultimately, it is clear that as cell and gene therapies continue to take hold in the health care landscape, there are a myriad of challenges for manufacturers to consider. However, integrated data, initially collected in clinical trials and then captured throughout a therapy’s life cycle, is the strong, connective tissue that can alleviate stakeholder concerns regarding safety and efficacy, and help overcome perceived barriers of various stakeholders. A comprehensive data strategy, implemented pre-launch and in partnership with key stakeholders, can make the difference in a product’s success or failure – and, more importantly, in patients’ lives.
Michael Eaddy, PharmD, PhD, is Vice President, Scientific Consulting at Xcenda, a part of AmerisourceBergen. Having spent the last 16 years leading the Real World Evidence consulting practice, Dr. Eaddy’s team has helped manufacturers generate evidence-based insights, as well as apply data analytics, to support their products’ clinical and economic value propositions. For more actionable insights on the potential barriers to commercializing cell or gene therapies and associated solutions, download AmerisourceBergen’s latest white paper, “Commercializing Cell and Gene Therapies.”
Filed Under: Drug Discovery