// . //  Advancing Science And Technology For Everyone //  Creating A Scalable Cell And Gene Therapy Ecosystem

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.

Pulling The Right Levers

There will likely be a significant upswing in cell and gene therapies coming to market. Last year, 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 recent analysis from the Marsh McLennan Agency estimated that 100,000 patients in the US alone will be eligible for cell and gene therapy by 2025. We expect 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:

Production: Recognizing that cell therapy and gene therapy have unique manufacturing processes, a few shared obstacles prevent the industry from keeping pace with demand. Among the most pressing issues are:

  • Process novelty: Due to the novelty of the science, cell and gene therapy manufacturing processes are immature and the regulatory landscape is fast evolving. In addition, several of these therapies are targeted towards diseases with high unmet needs and have fast track designation by regulatory authorities. This creates double pressure when moving from clinical to commercial grade product, eventually leading to higher COGS and causing launch delays.
  • Standardization: The industry needs to embrace a model for not just sharing but adopting best practices. There’s some movement towards this aim. 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. We are likely to see a greater push from regulatory bodies as well. A Food and Drug Administration advisory board last year homed in on the need for standardizing analytics and controls for AAV therapies, for instance.
  • Logistics: The COVID-19 pandemic exposed problems in the supply chain. Like virtually every industry, a reliance on just-in-time ordering caused major disruptions as 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 needed for gene and gene-modified cell therapies. They are also a key ingredient in some COVID-19 vaccines, which were given priority. Building a more agile supply chain will be key as the pharmaceutical industry braces for future disruptions.
Exhibit 1: Sizable growth expected in Global CGT Market

Regulatory and payer frameworks: Applying frameworks that were designed to assess the safety and efficacy of conventional drugs to cell and gene therapies is impeding the pace of innovation. There are key areas across these frameworks need to evolve in order to limit redundancies and fully drive value from innovation:

Exhibit 2: Challenges for cell/gene therapy outcomes contacting
  • Pricing: High price tags and upfront cost of cell and gene therapies are challenging payer affordability across the globe. There is an increasing recognition that such therapies will require and are most suitable for newer contracting approaches, such as risk pools, outcomes-based agreements amongst others. Approaches such as outcomes based agreements will require solving for building a data ecosystem that better understands real world value and creating the right incentives
  • Real-world data: Regulators and payers need to align on real-world data collection and generating evidence to demonstrate long-term value for safety and efficacy. They traditionally keep a healthy distance from each other – regulators are more focused on trial outcomes and labeling and payers more focused on formulary access. But misalignment across these two parties can create setbacks for the industry. For example, in case of Zolgensma, FDA labelling allowed for use in children below the age of 2, although the trial data only covered infants below the age of 6 months. This created a key challenge for payers that were under pressure to reimburse according to the label, with limited evidence. In addition, many other disease areas, such as neurodegenerative diseases, lack tangible endpoints that can be used to assess real-world value of these therapies. That can result in a disconnect between what regulators consider as acceptable endpoints and what payers value. Greater collaboration between regulators and payers will streamline evidence generation needs and help scale innovative contracting models.
  • Safety: Regulators need to develop more flexible frameworks for assessing the safety profile for CGTs and to keep pace with scientific discovery. Small changes in manufacturing processes have required additional studies, leading to setbacks in launch timelines and additional costs to pharmaceutical companies, which eventually gets passed down to payers in higher price tags. Patient safety should never be compromised but the need for additional studies, longer duration, and larger trials needs to be considered with development costs and time-to-patient access in mind. It is also important to pursue regulatory harmonization to create a more simplified path toward broad adoption of a drug. The World Health Organization in 2021 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, especially as the products start to make their way to those markets.
  • Improved engagement: Creating more productive dialogue between the three entities would move drug development from being purely transactional to one where pharmaceutical companies get important and constructive feedback that can be used in real-time to make significant improvements to the process. We have seen some positive movement in this direction from the FDA, but more needs to be done to unlock full potential.

Capable healthcare delivery system: Stronger linkages between providers and pharmaceutical companies are required to ensure cell and gene therapies become more widely adopted. Three components stand out:

  • Right patient, right time: The mantra applies here just as is does in other aspects of care delivery. While the number of people globally with a rare disease exceeds 300 million, identifying individuals is tricky. About 1 in 10 people in the US are estimated to have a rare disease. And diagnosis takes time — an average of 6 to 8 years for children. Since these patient populations are not clustered, stakeholders need to partner around such things as decentralized trial models which reduce the burden on patients to travel long distances.
  • Right team, right location: When selecting clinical partners, manufacturers should weigh a health system’s referral network to ensure patient access, similar to what exists for transplant and joint replacement procedures. It’s important that those networks include clinicians who are trained in genetic testing, administering complex therapies, and able to identify the right patients for an intervention. The UK’s Advanced Therapy Treatment Centre Network is an example of this in action. Among other things, ATTC developed a training program aimed at helping the UK healthcare workforce be ready to utilize novel treatments. Picking the right facility is key as well. For instances, clinical sites must have the correct storage units and sterile rooms. The distribution and handling of COVID-19 vaccines exposed several gaps in provider readiness when it comes to storage capabilities.
  • Right data: Across all stakeholders, a robust data infrastructure is required so information can be collected and analyzed in real time. This includes, but is not limited to, patient registries and patient monitoring to track safety and efficacy information. As artificial intelligence and machine learning become more prevalent in healthcare, stakeholders can also tap into these technologies to conduct predictive modeling, both 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.