By Walter Colasante, Pascale Diesel, and Lev Gerlovin, CRA
Progress in development of gene and cell therapies around the world has potential to transform standards of care for a range of diseases and address significant areas of unmet need in healthcare over the coming years. In the U.S. alone, almost 20 gene and cell therapy products have been approved thus far,1 with many other development programs reaching later clinical stages. The technology platforms of many of these drugs also offer the potential for curative efficacy and expansion for use in multiple indications.
Along with significant promise, gene and cell therapies also present a range of characteristics that can increase risk and cost, and thereby limit prospects for sustainable commercial success. Factors including complex and lengthy manufacturing requirements, very small patient populations, and short duration of treatment with curative outcomes that will reduce the pool of appropriate patients for treatment can have a significant impact on commercialization strategies. Many new drugs also lack evidence of durable long-term efficacy and safety, generating concerns among stakeholders, including regulators, clinicians, patients, payers, and industry partners. Examples of gene and cell therapies launched thus far indicate that commercial success can be a challenge even in cases where drug developers win regulatory approval. Among 10 novel gene and cell therapies approved in Europe since 2009, only six are still commercially available today.2 The remaining four (ChondroCelect, MACI, Provenge, and Glybera) were all withdrawn from European markets due to failed commercialization efforts.2 Recently, our team at CRA conducted an analysis of the challenges associated with go-to-market models for gene and cell therapies. This review strongly indicates that traditional commercial and marketing strategies may not be directly transferable for maximizing chances of success for many of these new drugs. Companies advancing these clinical development programs will need to consider new or significantly modified commercialization models while also embracing advanced technologies to maximize efficiency and continually meet production requirements.
Understanding The Commercial Challenges
Fundamental challenges in commercialization include costs and limitations in production methods. In just one example, producing autologous therapies such as chimeric antigen receptor T (CAR T) cells or stem cell therapies requires a process that must be replicated in individualized batches, which can present challenges in efforts to scale up production to meet global demand. The administration of these therapies can also present complications. For autologous treatments, a sample is taken from the patient, sent away for processing and modification (often to a single location regardless of geographic origin), and then dispatched back to a designated treatment center for re-administration to the patient. This process requires strict controls and quality standards, including traceability and a robust and reliable chain of temperature control. Planning for this process can mean considerable procedural and regulatory hurdles related to licensing, monitoring, and troubleshooting.
In addition to raising concerns among clinicians and patients, the lack of robust and conclusive long-term safety and efficacy data for many gene and cell therapies also presents challenges to regulators. When a U.S. Food and Drug Administration Advisory Committee unanimously recommended approval of Spark Therapeutics’ Luxturna for treatment of inherited retinal disease in October 2017,3 they cautioned that a lack of long-term follow-up data makes it unclear whether efficacy could diminish over time. They also raised questions about the potential for future adverse events not demonstrated in clinical research.4 Limitations on data can also fuel the perception that some gene and cell therapies do not provide significantly increased clinical value over existing therapies, making it difficult to justify often-high prices. To address any limitations on available data, regulators and payers often require companies to establish and maintain cumbersome and costly programs in patient monitoring and real-world data capture and reporting.
Companies working to commercialize gene and cell therapies may also face challenges in identifying and effectively targeting stakeholders. In many traditional models, marketing and advertising budgets and large sales operations can be leveraged to communicate the benefits of therapies to clinicians, healthcare providers, and patients. But this conventional approach is often not suited to gene and cell therapies, which may require a more tailored marketing strategy to effectively target very small patient populations with distinctive characteristics. Drug developers may evolve their conventional models to new channels and new content to meet the unique needs and stakeholder populations associated with gene and cell therapies in the years ahead.
Emerging Strategies To Support Commercialization
Drug developers are working to identify and implement a range of adaptive commercialization strategies that address these and other challenges while simultaneously embracing the distinct advantages that gene and cell therapies can offer.
1. Fast And Flexible Manufacturing And Supply Chain
Shorter duration of treatment associated with some gene and cell therapies can mean that both production and pricing models based on longer-term or lifetime dosing may not be applicable or adaptable. Pricing will need to reflect the fact that duration of treatment may be a matter of days or weeks versus years, more in line with medical innovations than with traditional drugs. In addition, approval of a potentially curative therapy may require a rapid spike in production that is not sustained over the long term. Both factors may require previously unnecessary levels of flexibility in production and distribution. Many industry insiders expect that, as gene and cell therapy development programs progress, there will be greater demand for advanced innovative production and distribution technologies, including, among others, advanced cryopreservation tools and services. Companies will need to identify engineers and other skilled technicians with the ability to identify and operate the technologies necessary to support production goals. They will also need to plan for intensive and potentially short-term changes in production capacity early in the product life cycle.
2. More Precise Patient Targeting
To facilitate commercial success, it will be necessary for companies to support clinician efforts to screen and identify appropriate patients quickly at all stages, from clinical development through commercialization. Widespread, continuous, and precise biomarkers and related diagnostics will become essential tools.5 Predictive analytics will also be important to define appropriate patient cohorts and then use that information to design and implement effective marketing and access plans. Claims data analyses of diagnoses and procedures at the local level will have to provide invaluable input when mapping the patient journey and designing a marketing and commercial strategy to be in sync with the patient experience. To support commercialization goals, manufacturers should also consider using predictive analytics to inform strategic decisions on the appropriate number of treatment sites, where they should be located, and whether and how they could facilitate delivery of gene and cell therapies directly to patients.
3. Collaborating With The Right Stakeholders
Many manufacturers of gene and cell therapies are also now turning to multidisciplinary stakeholders, including healthcare providers (HCPs), patient advocacy groups, patients, and clinicians, who can provide important perspectives and demands related to market adoption and commercial strategies. They turn to patient advocates to build precise assessments of the benefits and burdens of different drug delivery methods and, in some cases, to assess treatment protocols and dosing options and even some issues related to distribution, treatment site location, and longer-term patient monitoring. Stakeholders can also offer insights that can impact market access after product launch and support decisions related to pricing. In one example, the Duke-Margolis Center for Health Policy consortium in Washington, D.C. was created to bring together gene therapy manufacturers, payers, patient advocates, HCPs, and regulatory and policy experts to explore the feasibility of innovative payment models,6 which industry is quickly realizing may be necessary to support reimbursement of many gene and cell therapies. To maximize the benefit of these collaborations, gene and cell therapy companies now often reach out to a broad range of stakeholders early in the drug development process and maintain active engagement throughout the planning and execution phases of commercialization efforts.
4. Seeking New Opportunities For Growth
To increase the chances of commercial success, companies developing gene and cell therapies should work to identify and pursue opportunities for growth where possible. Many experts agree that these drug developers should focus initial commercial efforts on the U.S. and EU and then expand to other geographic areas once they establish best practices, recognizing that this approach will depend on the global prevalence of a target disease. However, in some cases, gene and cell therapy companies might also target less developed markets where new curative therapies can be rapidly positioned as standard of care without the need to first consider incremental advances in treatment or symptom management.
Some gene and cell therapies present a diversified development platform with a unifying focus that can create additional commercial opportunities. Companies should consider adopting technologies and production processes that can be adapted for use in different therapeutic areas in the future. They might also conduct research initiatives to better understand genetic factors associated with many diseases, following the models used in the Human Genome Project and the International HapMap Project. This type of research can lead to more gene and cell therapies, with the potential to expand treatment to additional indications, potentially including disease states with large patient populations.
While some new best practices to support gene and cell therapies are already in place or emerging, many companies working to develop these therapies will need to rethink the structure of their go-to-market models. Innovative, high-value processes and technologies that focus on speed, precision, and customization will be essential competitive advantages. Many companies will also need to consider collaboration with and support from a wide range of stakeholders, including patient advocates, HCPs, and payers. Successful commercial planning will also require companies to identify and plan for the full range of commercial opportunities for their technology platforms. With these new approaches, industry has the potential to optimize both patient access and commercial opportunities associated with the new generation of promising gene and cell therapies, many of which will be available to patients in the near future.
- FDA, Approved Cellular and Gene Therapy Products, available at https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/default.htm.
- Timothé Cynober, “Why Are There Only 10 Cell and Gene Therapies in Europe?,” Labiotech.eu, April 4, 2018, available at https://labiotech.eu/atmp-cell-gene-therapy-ema/.
- Emily Mullin, “FDA Vote Sets Stage for Gene Therapy’s Future,” MIT Technology Review, October 12, 2017 available at https://www.technologyreview.com/s/609075/fda-vote-sets-stage-for-gene-therapys-future/?set=609105.
- FDA, “FDA Advisory Committee Briefing Document, Spark Therapeutics Briefing Document,” October 12, 2017, available at https://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/bloodvaccinesandotherbiologics/cellulartissueandgenetherapiesadvisorycommittee/ucm579300.pdf.
- Cynthia A. Challener, “Cell and Gene Therapies Face Manufacturing Challenges,” BioPharm International, January 1, 2017, available at http://www.biopharminternational.com/cell-and-gene-therapies-face-manufacturing-challenges.
- Gregory Daniel et al., “Advancing Gene Therapies And Curative Health Care Through Value-Based Payment Reform,” Health Affairs, October 30, 2017, available at https://www.healthaffairs.org/do/10.1377/hblog20171027.83602/full/.
About The Authors:
Walter Colasante, Pascale Diesel, and Lev Gerlovin are VPs in CRA’s Life Sciences Practice. Colasante has worked extensively in both the pharmaceutical and consulting industries and across a range of therapeutic areas including oncology, the central nervous system, and rare diseases. Diesel has worked in global development, marketing, planning, and business development and has over a decade of strategic consulting experience focusing on portfolio optimization and valuation. Gerlovin has more than 11 years of experience in life sciences strategy consulting, focused on commercial and market access strategies. The authors wish to acknowledge the contributions of Stephanie Donahue and Michael Krepps to this article.
The views expressed herein are the authors’ and not those of Charles River Associates (CRA) or any of the organizations with which the authors are affiliated