A Drug Development Guide for Cell and Gene Therapies

Cell and gene therapies (CGTs) comprise a new class of therapeutics built on the idea that there’s no one-size-fits-all approach to treating cancer, immune conditions and other diseases. Studies show that cell therapies — which use immune cells and other types of cells, derived both from the patient and from other sources — can be used to help patients live better, healthier lives. Gene therapies change gene expression — or the properties of living cells — for therapeutic use. A number of CGTs are approved by the U.S. Food and Drug Administration for cancer, immune diseases, genetic conditions and rare diseases. Keep reading to learn more about these unique considerations and strategies for CGT development.

It’s important that drug developers have the expertise and experience to properly navigate the complex landscape of cell and gene therapies, from early development planning to post-marketing follow-up strategies. Drug developers with a comprehensive, integrated evidence-generation strategy will have a competitive advantage. As well, they can bring these potentially transformative therapies to more patients as efficiently as possible.

A few keys to success in CGT drug development include:

• Planning ahead to ensure a solid research and development infrastructure, including asset planning, use of natural history studies, competitor analysis and an understanding of the pricing landscape.
• Addressing regulatory, health technology assessment (HTA) and market access concerns, including the specific requirements of regulatory agencies; planning for broader research, including real-world studies, beyond pivotal trials to provide evidence for reimbursement; and myriad other stakeholder (e.g., patients, caregivers) concerns and considerations for how a therapy will be reimbursed.
• Identifying long-term follow-up strategies that enable the demonstration of safety, effectiveness, durability and value over time.

Early Planning Must-Dos for Cell and Gene Therapies

Early development consulting and evidence planning is central for CGT development. Drug developers should aim to find a partner that supplements and accelerates research and development (R&D) and supports research infrastructure for the best R&D outcomes.

Key capabilities in the early stages of development for cell and gene therapy products include:

Asset planning. Assessing potential assets and identifying a path forward is an essential step in the CGT research and development process. This initial planning phase provides biotech companies with clarity regarding the target for their potential asset, identification of the decision-makers and ways in which the asset must be managed over time. Questions to consider asking include:

• Is there more than one indication, or more than one target population?
• Will the CGT developer find a partner to market at a certain point in the product lifecycle, or will the developer take it to full market access themselves?
• What price could the new treatment command? What kind of uptake of the product could be expected?

Leveraging natural history studies to fill knowledge gaps. Natural history studies provide information on disease characteristics and reveal how a disease progresses over time with or without current available treatment options, which informs clinical product development. The introduction of genetic testing to natural history studies has expanded their potential value by:

• Identifying genetic profiles of the patient population,
• Providing screening criterion to detect target populations and disease subtypes, and
• Recognizing sub-populations that are less or more likely to benefit from new therapies.

Researchers can also identify relevant existing and novel endpoints from these study results and use them to inform clinical outcome assessments, such as patient-reported outcome measures. For example, health-related quality-of-life endpoints may require researchers to measure changes in mobility or deterioration after receiving the study treatment. The instruments used to measure these endpoints require experienced health outcomes researchers to ensure they are designed and validated to be acceptable to regulatory and HTA agencies, and selected to maximize information while minimizing patient survey burden.

In addition, because many cell and gene therapies don’t have a comparator arm, researchers can design natural history studies to use the resulting data as an external comparator to supplement clinical evidence, enabling clinicians and payers to assess the benefits, safety and cost impacts of the treatment. Where non-CGT treatments are available in an indication, payers may see those as relevant treatment options. In those cases, it is possible to use accepted statistical technologies to leverage published clinical trial data to inform indirect treatment comparisons, thus providing a comparator to a single-arm trial.

Identifying primary competitors. Competitor analysis enables companies to understand the breadth of drug developers that already have therapies on market or in development for the same disease, as well as the metrics in which they can differentiate themselves. For example, there could be more than one company targeting the same or similar gene that could intervene with the disease trajectory. With robust analysis, biotech and pharmaceutical companies can plan their evidence strategies to gain an edge in R&D, commercialization and pricing.

Understanding patient-focused study protocols. Patients are more active than ever in their own care. Patient-centric health care models are becoming the new norm, with services designed to incorporate and embrace patients’ wants, needs and preferences. Evidera provides services that elucidate the patient experience at various stages in the product lifecycle to inform a patient-focused drug development strategy. This can be especially important in cell and gene therapy drug development.

Novel study designs. Innovative designs for research studies can accelerate new transformative therapies. Examples of novel research designs include:

• The use of real-world data for external control arms in which a single-arm study is being used in clinical trials.
• Decentralized studies in which a patient may only go to the doctor’s office or a study site occasionally, or not at all.
• The use of virtual research. A virtual research coordinating center, or VRCC, can extend study site capacity with a central primary investigator for enhanced efficiency and remote data collection, increasing speed of patient screening and enrollment. This enables decentralized approaches and data collection for studies, including natural history and long-term follow-up.

Regulators, HTA bodies and payers all require long-term follow-up studies — anywhere from five to 15 years — of CGT recipients. Therefore, innovative, decentralized services that minimize patient burden in cell and gene therapy trials and support patients where they live will enable compliance and retention. Novel designs can also be useful to ensure that the required information is gathered with patient-centricity in mind, such as having home health nurses visit the participant to draw blood and collect data, or enabling patients to sign consent forms, answer questions or submit data online.

Regulatory, HTA and Market Access Considerations

Knowledge of the regulatory landscape and market access issues is crucial to successful commercialization of drugs in development. There are countless considerations for therapy introduction to the market and reimbursement, and biotech companies may not have the internal resources, knowledge or experience needed to scrutinize them all. A partnership with an evidence-based provider like Evidera is critical for accessing guidance that advances the process, pinpoints the evidence needed, and provides the means to generate and communicate the value of pharmaceutical products.

Strong regulatory and market access strategies can maximize the chances of a drug successfully making it to market. Pharmaceutical developers who avail themselves of expert consultation in strategy development are better positioned to:

• Launch R&D programs in CGT, including pediatric drug development.
• Undertake integrated scientific advice to align multiple stakeholders, de-risk clinical development, formally pressure test aspirational value propositions and accelerate time-to-market access.
• Develop an integrated evidence development plan and gap analysis early in the planning stages that outlines the evidence required for all key stakeholders, including regulatory agencies, HTA bodies, payers and patients. Early consideration will allow companies to avoid delays in the future caused by unexpected requests for further evidence.
• Perform value demonstration using data-driven insights to develop clear, evidence-based messages to concisely communicate the value of a therapy to health care decision makers. The transformation of evidence to value drives actionable insights that optimize reimbursement.
• Conduct health economics modeling, such as cost-effectiveness and budget impact analyses, suitable for submission to reimbursement bodies, and select the right treatment comparison for CGTs to demonstrate any cost savings and added value. Fiscal modeling can be especially relevant for CGTs — particularly those that could prevent or alleviate disabilities — by considering a broader view of the health care system and identifying a therapy’s overall benefit to the entire community. With experience in novel treatments, our market access experts can help identify the critical evidence needed to stay ahead of evolving demands from global payers and HTA bodies.
• Implement patient-centric data collection. High-quality, patient-centered data is becoming increasingly imperative for regulators and other stakeholders to understand the safety and benefit of treatments. Detailed and rigorously tested processes for collecting and evaluating patient-reported outcomes are imperative for data to meet the demands of regulatory agencies.
• Identify data gaps. Payers often require evidence not collected during clinical trials, such as aspects of costs, treatment patterns and quality of life, which is important in conveying a therapy’s value story in its reimbursement dossier. Some of this evidence can be sourced from published literature, but additional research is often necessary and requires early engagement and planning to obtain the most comprehensive and persuasive evidence.
• Harness the power of real-world evidence (RWE) in clinical trials and post-approval regulatory monitoring. Launch and reimbursement strategies are crucial for CGT success and demonstrating the true value of your product. Therefore, it’s vital to supplement your clinical data with real-world evidence.
• Assess centers of excellence to prepare for launch. In many cases, specialized centers are required to administer novel therapies. Identifying these centers and what support and training may potentially be needed in advance of launch is critical, particularly in rare disease treatments where patients may be widespread.

In addition to these benefits, there is also a critical need to understand and prepare for continual changes and updates in regulations and requirements that may affect development and commercialization plans for cell and gene therapies. Two significant examples include:

Working through the United Kingdom’s Innovative Licensing and Access Pathway (ILAP) to accelerate CGT research and development. In the U.K., the ILAP provides an accelerated infrastructure for medicinal products that meet specific criteria, which includes cell and gene therapies. This includes a special process for early licensing, as well as guidelines for health technology assessments that are required for reimbursement and market access for patients. CGT is a huge area of interest in ILAP, and an experienced provider of evidence-based solutions will enable biotech and pharmaceutical companies to expertly navigate this emerging landscape.

Monitoring the outcomes from ongoing consultations for the new European HTA Regulation to proactively prepare for future Joint Clinical Assessments (JCAs). In late 2021, the European Commission (EC) announced the new regulation for health technology evaluation. As part of this new regulation, all products with an indication in oncology or considered advanced therapy medicinal products (ATMPs), which include cell and gene therapies, will be required to undergo a European-wide JCA. Ahead of this, several consultations on the process and methodology to be used are being carried out. A well-versed partner in HTA policy and methodology will support health technology developers in navigating the outcomes of these consultations and extracting the implications for a company’s CGT pipeline to efficiently prepare for future JCAs in 2025.

Long-Term Strategies

For drug developers, getting to the market is not the final step. Commercialized drugs require long-term follow-up studies to ensure safety and efficacy, and they must be well-thought-out in advance. It is also important to consider special populations for your CGT, such as pediatrics and pregnant women.

Post-approval safety experts can advise on post-marketing requirements and commitments needed.

• Long-term follow-up studies. Long-term follow-up studies can vary for cell and gene therapies but last anywhere from five to 15 years. These studies answer questions about long-term safety and durability, satisfy regulatory requirements, and enable payers to determine if the therapies are worth the cost.
• Safety. For patients and regulatory agencies alike, there are specific aspects of safety, such as immunological safety, that are closely monitored to reduce risks. These safety-related aspects persist after the CGT has obtained regulatory approval.
• Pediatric research studies. Pediatric populations have specific requirements and needs. Studies of CGT in pediatric populations often start in adults, and then branch out to a pediatric age group. This allows researchers to study the benefits of a therapy in children once safety and efficacy are shown in adults. Pediatric studies, therefore, need workable long-term strategies that can accommodate this model.
• Long-term pricing strategies. Pricing changes over the lifetime of a product, and decisions will need to be made after patent expiration or due to possible generic or biosimilar product threats. It is important to have a solid understanding of possible price levels at launch, how price develops over time and what pricing options are available after a product’s patent expires.

The Bottom Line

Cell and gene therapy is an exciting avenue for the pharmaceutical industry to advance new, effective therapies that target and treat devastating diseases. The Alliance for Regenerative Medicine found that the amount of cell and gene therapy developers jumped 10 percent from 2019 to 2020 – and our experts expect continued growth in this space.

That is why it is critical that companies create early, strategic plans that address all aspects of CGT development — from early development through post-approval — so that they are supported in getting advanced therapies to market and beyond.

Working with a proven provider of evidence-based solutions, such as Evidera, a part of the PPD clinical research business of Thermo Fisher Scientific, ensures both efficiency and alignment of the drug development strategy. Without proper considerations, CGT developers may face avoidable delays in life-changing scientific advancements. Evidera’s experts are here to make sure that doesn’t happen.