Optimism abounds about the potential for cell and gene therapies to revolutionize patient care. We’ve seen groundbreaking drugs come to market for treating spinal muscular atrophy, metachromatic leukodystrophy, and retinal disease. Advances in CAR-T cell therapy are giving cancer patients new confidence. Every breakthrough in research holds promise for better patient outcomes, and not just for those with rare diseases; increasingly, there’s hope that discoveries will result in improved care for more common conditions and even lead to one-time cures.
Tempering that optimism is a mix of systemic obstacles that limit the effectiveness and reach of these innovations. Many new drugs come with hefty price tags. Gene therapies for treating hemophilia A and B carry a $2.5 million lifetime cost. Zolgensma, a treatment for spinal muscular atrophy, hit the market in 2019 at more than $2 million per patient. Zynteglo, used to treat the rare blood disorder beta thalassemia, reportedly costs $2.8 million per patient. Equally as challenging is the dearth of data on long-term health benefits of most experimental therapies.
At the same time, there are significant operational challenges, including provider frustration with the lack of standardized workflows, training, and risk assessments. If cell and gene therapies are going to become mainstream stakeholders across the industry — pharmaceutical companies, payers, providers, and regulators — must work together to create a more affordable, scalable, and sustainable model.
Three priorities for scaling cell and gene therapies
There will likely be a significant upswing in cell and gene therapies coming to market. In 2021, 582 CGT clinical trials were initiated and an additional 138 started in Q1 of 2022. In total, 2,093 clinical trials were underway as of the end of June, according to the Alliance for Regenerative Medicine. And a 2022 analysis from Marsh estimated that 100,000 patients in the US alone would be eligible for cell and gene therapy by 2025. At the time, we expected new drug approvals to boost the global CGT market 55% by 2028, hitting nearly $14 billion.
But ensuring this growth has the furthest possible reach and impact is another issue. We’ve identified three broad areas that must be addressed to bring scale to the cell and gene therapy market.
Overcoming cell and gene therapy manufacturing challenges
Although cell and gene therapies have distinct manufacturing processes, they face several common challenges that prevent the industry from keeping pace with demand. Among the most pressing are:
- Production: Due to the novelty of the science, cell and gene therapy manufacturing processes are still immature, while the regulatory landscape continues to evolve rapidly. In addition, several of these therapies target diseases with high unmet medical needs and have received fast-track designation from regulatory authorities. This creates additional pressure when transitioning from clinical- to commercial-grade products, ultimately increasing the cost of goods sold (COGS) and delaying launches.
- Standardization: The industry needs to move beyond sharing best practices to adopting them more widely. Some progress is already underway. The Alliance for Regenerative Medicine (ARM) and the National Institute for Innovation in Manufacturing Biopharmaceuticals are spearheading Project A-Cell and Project A-Gene, both of which call for standardizing equipment, methodologies, and testing. Regulatory bodies are also likely to place greater emphasis on standardization. For example, a Food and Drug Administration advisory committee highlighted the need to standardize analytics and controls for AAV therapies.
- Logistics: The COVID-19 pandemic exposed vulnerabilities in supply chains. As in virtually every industry, reliance on just-in-time ordering caused major disruptions when supply chains came to a halt in 2020 and 2021. A shortage of viral vectors further hampered cell and gene therapy production. Viral vectors are essential for gene and gene-modified cell therapies and are also a key component of some COVID-19 vaccines, which were given priority. Building more agile supply chains will be critical as the pharmaceutical industry prepares for future disruptions.
Modernizing cell and gene therapy regulation and reimbursement
Applying regulatory and payer frameworks designed to assess the safety and efficacy of conventional drugs to cell and gene therapies is slowing the pace of innovation. Several aspects of these frameworks need to evolve to reduce redundancies and fully realize the value of innovation:
- Pricing: The high prices and upfront costs of cell and gene therapies pose affordability challenges for payers worldwide. There is growing recognition that these therapies require newer contracting approaches, such as risk pools and outcomes-based agreements. Implementing these approaches will require building a data ecosystem that better captures real-world value and creates the right incentives.
- Real-world data: Regulators and payers need to align on real-world data collection and evidence generation to demonstrate long-term safety, efficacy, and value. Traditionally, the two have operated largely independently, with regulators focusing on trial outcomes and labeling, and payers on formulary access. However, misalignment can create setbacks for the industry. For example, the FDA labeling for Zolgensma allowed its use in children under the age of 2, although clinical trial data covered only infants under 6 months. This created challenges for payers, who faced pressure to reimburse treatment in line with the label despite limited supporting evidence. In addition, many disease areas, including neurodegenerative diseases, lack tangible endpoints for assessing the real-world value of these therapies. This can create a disconnect between the endpoints regulators consider acceptable and those payers value. Greater collaboration between regulators and payers will help streamline evidence generation and support the broader adoption of innovative contracting models.
- Safety: Regulators need to develop more flexible frameworks for assessing the safety of cell and gene therapies while keeping pace with scientific advances. Even small changes in manufacturing processes have required additional studies, delaying launches and increasing costs for pharmaceutical companies, which can ultimately be passed on to payers through higher prices. Patient safety must never be compromised, but requirements for additional studies, longer study durations, and larger trials must also be considered in the context of development costs and timely patient access. Greater regulatory harmonization is also important to simplify the path toward broader adoption of these therapies. In 2021, the World Health Organization called on officials in high-income countries to ensure that regulators in low- and middle-income countries are familiar with the scientific and regulatory issues surrounding cell and gene therapies, particularly as these products begin entering their markets.
- Improved engagement: More productive dialogue among regulators, payers, and pharmaceutical companies would help shift drug development from a largely transactional process to a more collaborative one. This would enable pharmaceutical companies to receive timely, constructive feedback and make meaningful improvements throughout development. While the FDA has made some progress in this area, further collaboration is needed to unlock the full potential of these therapies.
Preparing healthcare systems to deliver cell and gene therapies
Stronger collaboration between healthcare providers and pharmaceutical companies is essential to support the wider adoption of cell and gene therapies. Three key components stand out:
- Right patient, right time: This principle applies to cell and gene therapies just as it does to other aspects of healthcare delivery. More than 300 million people worldwide live with a rare disease, yet identifying affected individuals remains challenging. In the US, an estimated 1 in 10 people have a rare disease, and diagnosis can take time — an average of six to eight years for children. Because these patient populations are geographically dispersed, stakeholders need to collaborate on approaches such as decentralized clinical trial models that reduce the need for patients to travel long distances.
- Right team, right location: When selecting clinical partners, manufacturers should consider a health system's referral network to ensure patient access, similar to the networks established for transplant and joint replacement procedures. These networks should include clinicians trained in genetic testing, administering complex therapies, and identifying patients who may benefit from treatment. The UK's Advanced Therapy Treatment Centre (ATTC) Network provides an example of this approach. Among its initiatives, the ATTC developed a training program to help prepare the UK healthcare workforce to deliver novel treatments. Selecting the right facilities is equally important. Clinical sites must have appropriate storage units and sterile rooms, for example. The distribution and handling of COVID-19 vaccines highlighted gaps in provider readiness, particularly in storage capabilities.
- Right data: A robust data infrastructure is essential for stakeholders to collect and analyze information in real time. This includes patient registries and monitoring systems to track treatment safety and efficacy. As artificial intelligence and machine learning become more prevalent in healthcare, stakeholders can also use these technologies for predictive modeling of disease prevalence and progression.
There is a strong push for cell and gene therapies to grow rapidly over the next several years. But for the market to thrive and have far-reaching impact, stakeholders must embrace new ways of partnering and take explore creative approaches to overcoming long-standing obstacles. Staying with the status quo is not only damaging for patients but can also push back the investment being poured into the market.