Dr. Izaskun Elorza
Senior Medical Director, Cell and Gene Therapy
Parexel
Cell and gene therapies (CGT) are a heterogenic group of therapies based on the physiological capacities of the cells and the extraordinary advances of genetic technology, which give them new or improved therapeutic functions. Moreover, platforms based on in-vivo gene delivery by vectors, CRISPR editing, and RNA approaches can change the patient's genetic profile. Each day, we read about more sophisticated options in this area, most looking for new indications or overcoming the limitations of the approved autologous cellular therapies.
The majority of CGT is currently focused on oncology, with success in hematologic malignancies and a high unmet need, in solid tumors. CGT also target genetic disorders and cardiovascular, neurodegenerative, and infectious diseases. Some data confirm that CGT is the present and future in therapies and has come to stay: at least 16 of the top 20 pharmaceutical companies have CGTs in their pipeline. The FDA estimates 10-20 approvals per year by 2025, and more than 3,000 preclinical and clinical trials open.
Science has made an enormous step forward, but the goal should ultimately be to make them accessible to patients who could benefit from CGT and receive it within a reasonable time frame. Investigators, the general population, and payors are gradually accepting the medical benefits of CGTs. The infrastructure and human resources required to bring these therapies to market need to coordinate the knowledge and capabilities from pharma companies, contract research organizations (CROs), and sites.
The role of CROs in the last few decades has been vital for the efficient functioning of the biopharma industry. CROs gradually have extended their expertise across all therapeutic areas, from working with, and learning from, multiple companies. CROs can be a principal expert on global research efforts. They have comprehensive experience executing the complex and numerous phases of CGT research and development. On the other hand, some CROs have become interested in CGT biotech start-ups and are helping to facilitate a smoother beginning. The academic and emerging biotech companies usually are the ones to develop groundbreaking CGT projects but may lack the capabilities to expand clinical trials. CRO experience and expertise in conducting clinical trials and the desire to support state-of-the-art therapies can overcome CGT's main challenges.
The different nature of patients and therapy platforms in CGT projects needs an innovative design of clinical trials. The traditional randomized controls and dose-escalating schemes do not fit the small number of CGT subjects recruited and their life-threatening conditions. The studies can be strengthened using flexible and adaptative designs to reduce the duration and cohort size.
Every CGT product is unique, and every CGT company has its philosophy. Hence, from the beginning of the development pathway, companies need to work closely and be open with regulatory agencies to create efficient strategies for research and development. Understanding the requirements for approving one particular product is critical. The CRO's capabilities related to regulatory consulting, statistical, and data management services are compelling to complete the schedule. The extended geographic coverage of CROs helps strategic partnerships. The regulatory pathways for advanced therapies are still far from harmonized requirements, so CROs have invaluable importance in supporting companies as they expand across regions.
CGT trials require coordination with many specialists leading to highly complex site activation. CGT companies need to develop hospital networks to provide training, support governance systems, and guidance to encourage trust in CGT. The CRO ́s medical, operational, and solutions experts work with multidisciplinary teams to deeply understand the investigator team and unique internal processes, keeping a close and continuous relationship throughout the clinical trial. Supporting sites and investigators with medical expertise and logistics solutions can expand CGT to secondary care health centers. These community centers often have no experience with CGT but have strong clinical experience in treating and supporting patients and families.
Many of the centers and investigators conducting trials in CGT are coming from hematopoietic stem cell transplant units (HSCT) and blood and tissue banks, and have been building clinical and laboratory knowledge for many years with cellular therapies. In the last decade, the European and American Societies of HSCT have developed good practice guidelines that contain advice on donor evaluation, handling cellular products, and research with CGTs. The accredited FACT and JACIE institutions possess the appropriate requisites for early and long-term CGTs trials. These centers focus on hematology and genetic diseases as the main indications for allogeneic transplants.
Solid tumors have not been an indication for CGT or treated with cells until recently, so the novelty in the public consciousness and the complexity of logistics must be a challenge to motivate investigators and patients. Additional time and resources should be invested to qualify and train sites for genetic disorders and pediatrics trials.
Patients show broad acceptance of CGTs, but some variation exists between geographies, age, and educational level. The length of the trials, with follow-up to 15 years, the financial burden, and loss of connections with their primary treating doctor and friend networks contribute to adverse patient perceptions. The positive patient experience is critical for the patient, the site, and the study. The communication should be empathic and personalized, providing honest dialogue regarding trial uncertainties and clinical benefits to help set realistic expectations.
The insights of the patients undergoing CGT treatments and the real-world data determine the best way to tailor the communications tools to specific characteristics of the patients, families, and family advocacy. The collection, recording, and analysis of the patient's experience can provide CROs and biopharmaceutical companies with vital information to understand the complexity of the patient journey and the issues facing investigators and sites when making recommendations about CGT to their patients.
CGTs are disruptive to how clinical therapies and trials have been developed in the past. Patients, investigators, companies, and CROs will be faced with understanding and adapting to CGT across most therapeutic areas in a fast-growing and complex environment. The success path will be based on a positive patient experience, expert capabilities on clinical trials and the development of safe and accessible cell and gene therapy products.
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