As personalized medicine continues to progress, cell and gene therapy (CGT) development is poised to enable tremendous medical breakthroughs. Unlike traditional treatments which merely manage symptoms, CGT could treat the root biological cause of many diseases: the faulty genes.
“The cell and gene therapy space is truly exciting. What this ultimately means for patients and caregivers, and our ability to play an important part within this paradigm, is exhilarating,” said Dr. Panteli Theocharous, the global vice president and cell and gene therapy strategy lead at PPD.
With more than 20 years of experience in the pharma and biotech industries, Theocharous provides guidance on developing CGTs. He accentuates the importance of partnerships, data-driven approaches and patient-centricity in overcoming challenges.
Yet the path forward is filled with obstacles. In 2021, cell and gene therapy trials represented 40% of all clinical trial holds, nearly double the historical average. This marked increase was nearly twice the historical average. While about half of holds are eventually lifted, the increasing number indicates hints at challenges sometimes involved in CGT clinical trials.
Growing CGT investment
Meanwhile, interest in the field remains robust. In the decade leading up to 2020, six major pharmaceutical companies forged more than 50 CGT alliances and licensing deals worth more than $16 billion. They also spent approximately $38 billion on acquisitions, according to research from BCG. In addition, the market benefits from numerous alliances, licensing deals and acquisitions indicating strong interest and investment, as Pinsent Masons LLP has noted.
Between 2019 and 2021, nearly a third ($15.3 billion) of the $51.8 billion in total biotech venture capital funding went to CGT, according to a Frontiers in Public Health analysis.
Despite the significant investments, commercial entities in the CGT industry must strike a balance between high research and development costs, the complexity of the manufacturing process and the demand for specialized expertise. As Theocharous emphasized, managing potentially elevated costs requires building efficiencies in both the scientific process and product development. This approach is crucial as CGT expands its scope from addressing rare diseases to tackling chronic conditions.
The nature of these therapies — often administered once but having lifelong effects — can complicate their market valuation.
Robust growth predicted for cell and gene therapy market
Recent estimates indicate the U.S. spent around $1 billion on gene and cell therapies in 2020. According to Vision Research Reports, the global cell and gene therapy market size could hit $42.56 billion by 2030, growing at a CAGR of 39.42% from 2022 to 2030.
The price tag of individual therapies can be considerable. For instance, the wholesale acquisition cost of CAR-T cell therapies, used to treat certain B-cell lymphomas, is around $373,000. The total cost of care for a patient, including hospital stays and follow-up visits, averages $711,000 and can exceed $1 million in some cases. In November 2022, the price tag for an adenovirus-associated virus–based gene therapy for hemophilia B was set at $3.5 million. The drug is administered as a single infusion.
Complicating matters are the difficulty of quantifying lifelong benefits for patients and the high R&D costs often involved in gene and cell therapy development. The average cost to research and develop a successful drug is around $2.6 billion.
A recent study on the clinical-stage R&D costs for cell and gene therapies put the investment required to bring a new cell or gene therapy to market in a similar ballpark. After accounting for the attrition rate, the study estimated that cost of capital at 10.5%, is around $1.943 billion. In addition, gene therapies usually take longer to bring to market than traditional drugs, with some estimates pointing to a 15-year minimum for R&D.
Balancing innovation and compliance in cell and gene therapy development
Challenges in the CGT landscape: The rapid advances in CGT requires balancing innovation and compliance to proactively address challenges. Stakeholders must generate high-quality data while navigating a constantly-evolving regulatory landscape and strictly following regulatory guidelines to ensure CGT products are safe and effective.
Theocharous underscored the rapid scientific advances in CGT. “Scientific innovation is accelerating,” he said. “Companies are developing more sophisticated cell engineering and gene therapies while also collaborating closely with regulators.” He also emphasized that healthcare providers must not only keep up with these fast-paced developments but also navigate the complex ethical considerations that these therapies bring about.
Risks and technical challenges: As an emerging and experimental field, cell and gene therapy faces significant risks and technical obstacles. These include complications such as cancer, organ damage, or allergic reactions. Effectively delivering new genes into cells, ensuring their continued activity and avoiding unforeseen consequences also pose immense technical challenges. Researchers and clinicians must carefully weigh the benefits against the risks while improving the safety and efficacy of CGT.
Most gene therapies are designed to have permanent or long-lasting effects, increasing the likelihood of delayed adverse events. Accordingly, the FDA updated its guidelines in 2020 to recommend following patients for 15-20 years for studies using integrating vectors and genome-editing treatments, and at least 5 years for those using adeno-associated viral vectors. This extended follow-up aims to identify any delayed side effects, as noted in Nature.
Navigating the complex, evolving terrain of cell and gene therapy development
To navigate the CGT landscape, Theocharous advocates cultivating strong partnerships, robust data management and specialized talent. This includes the development of strategic alliances with regulatory agencies. In the CGT market, collaboration is key, as developers seek to make their businesses resilient to the economic headwinds they face. Furthermore, companies in the CGT industry need to adapt to changes in regulatory standards across different geographies. There are major differences in the volume of CGT activity across different geographic markets, with the US being where much of the innovation is focused, while Europe has shown signs of market stagnation.
According to Theocharous, the healthcare sector should develop strategic alliances with regulatory agencies, invest in advanced data management systems and recruit regulatory specialists.
A report by BCG notes that regulatory standards have tightened for the CGT industry in recent years. In 2020, six CGT programs were forced to delay development after the FDA requested more information about manufacturing processes. As the market trends toward consolidation, and with the potential of new regulatory landscapes owing to changes in European and U.K. pharmaceutical laws, the significance of close partnerships with regulatory agencies remains vital. Significant changes to the regulatory framework for CGTs are likely in both Europe and the U.K.
Theocharous suggested that fostering regulatory relationships should also coincide with a reduction in reliance on multiple third parties involved in the development of CGTs. “As we think about reducing the number of third parties the sponsors have to engage with within that ecosystem, we’re focusing on also reducing the whitespace when it comes to the development of these highly complex therapies,” he said.
The importance of engaging with payers and regulatory agencies
Beyond the technical and regulatory aspects of therapy development, Theocharous also emphasizes the need to strategically engage with payers. ‘The other area that I’m very passionate about is how we also engage and think about the strategy related to payers. Because ultimately, we want to ensure that patients get access to these therapies, post regulatory approval,” he said. He calls for the development of innovative payment models for these often costly therapies, emphasizing the crucial role of payers in the CGT ecosystem.
Regulatory bodies like the FDA and EMA obviously play a critical role in the CGT field. But regulators are not mere gatekeepers. Partnerships with such agencies can create a collaborative environment that enables quicker problem-solving and more efficient delivery of therapies to patients, Theocharous said.
Technological innovation and talent considerations
In an era where data volumes continue to set new records, Theocharous recommends tapping emerging edge technologies for efficient data collection, analysis and interpretation. These include data science, artificial intelligence (AI), machine learning and natural language processing (NLP).. PPD’s goal is to use such cutting-edge technologies for efficient data collection, analysis and interpretation, Theocharous said.
In addition to technology, Theocharous highlights the importance of attracting and retaining top talent for the development of innovative CGT therapies. He stresses the role of patient advocacy groups and emphasizes the continuous strategic growth of his organization in building and maintaining teams with the necessary expertise.
“We definitely focus on leveraging the right resources and talent. In some respects, we need to ensure that we are also developing the right tools to ensure our study teams are well-engaged, informed and set up for success,” he continued.
Talent considerations in cell and gene therapy
The reservoir of skilled CGT professionals needs to expand consistently “given the increased number of biotech companies in this space, the interest expressed by pharma organizations, and the rising number of clinical trials,” Theocharous stated. He emphasized that internal training is key to equipping study teams with the knowledge and skills they need to succeed.
Theocharous stressed the value of harnessing the knowledge and skills of their internal subject matter experts. “We leverage our internal SMEs and experts to be thought leaders. We think about the continuity of the process, points of escalation and ensuring that we are meeting the needs of the sponsors. This involves not only giving them the attention they require but also managing their expectations on the quantity of our output.”
“Cell and gene therapy requires a more personalized approach, more attention to detail, compared to small molecule drug development. We’ve recognized this over the years that we’ve been involved in clinical development,” Theocharous concluded. “It’s an evolving landscape, and our attention to detail in these highly complex therapies is paramount.”
Building a collaborative foundation to cell and gene therapy development
Theocharous indicates an optimistic outlook towards the CGT field, stating, “We should prepare ourselves for the growth and potential opportunities that this field will undoubtedly offer as time progresses.”
Theocharous highlighted the significance of integrated services in streamlining operations, saving time and cutting costs. This approach encompasses not only scientific development but also manufacturing and clinical development services.
Furthermore, Theocharous pointed out the importance of collaboration with regulatory bodies and beyond. “We need to broaden our scope to effectively engage with community-based hospitals and support these centers in meeting the required standards for participation in clinical trials,” he stated. “Our goal is to offer patients options for clinical trial involvement, which demonstrates our obligation and commitment to partner with site investigators and patients.”
Patient-centricity and stakeholder engagement
Theocharous said that “In the pursuit of innovation, we should always remember our principal aim: to enhance the well-being of patients.” He emphasized the significance of maintaining an active dialogue with all stakeholders, including patient advocacy groups, to ensure a patient-centered approach that prioritizes accessibility, affordability and insurance coverage.
Navigating the complex terrain of this emerging field goes beyond interacting with regulatory agencies. It calls for robust partnerships with Contract Research Organizations (CROs) and community hospitals. Theocharous sees CROs not merely as service providers but as integral partners in development. They have the unique capacity to transform sponsors’ scientific directives into actionable clinical trial protocols.
Furthermore, engaging diverse stakeholders, especially patients, is paramount. As we progress toward eliminating hereditary diseases, keeping patients’ needs and perspectives central should remain at the heart of the CGT ecosystem.
As the field of CGT matures, adopting a proactive approach, fostering strong partnerships and placing a firm emphasis on patient-centricity are strategies that will ensure compliance and drive innovation. “Our dedication and commitment to delivering these therapies for patients, navigating regulatory challenges, and fostering talent is crucial for the continued advances in modern medicine,” Theocharous concluded.