Innovative cell and gene therapies offer a potential cure to a wide range of diseases. Advancements of these therapies have aided in the development of immunotherapies in oncology, correction of genetic birth defects, and even have the potential of treating congenital diseases earlier than ever before.
While the market is set to reach $17.4 billion by 2026, patients are experiencing long wait times to access these critical treatments due to a number of factors. Most importantly, sponsors must navigate the ever-changing regulatory requirements for conducting the necessary clinical trials, ensuring patient safety, and collecting robust data to support their therapy’s benefits claim.
This will often require sponsors to timely interact with regulators to establish appropriate approval pathways that consider the unique characteristics of these therapies.
Here are a few strategies of how Sponsors take a proactive approach to solving the challenges that delay cell and gene therapies to market.
Marketing authorization application, appropriate reporting, follow up, and signal identification
Regulations around cell and gene therapy exist in order to ensure the best outcome for the patient, and to ensure a high quality product, no matter where or when the therapies are being performed. However, these strict regulations can present significant hurdles that must be meticulously managed.
When proposing cell and gene therapy development programs, sponsors should thoroughly outline all plans in advance based on thorough scientific data, and have in-depth knowledge on current similar approved products in order to better manage these regulatory hurdles as they arise.
Sponsors should also begin meeting with regulators as early as possible to discuss development plans prior. These meetings can be extremely productive in aiding in spotlighting common failure points before they occur. For instance by seeking regulatory advice when working towards supporting the first-in-human (FIH) data packages. According to research from the FDA, most, if not all, approved cell and gene products engaged in early regulator meetings for development.
Once a patient has received a cell and gene therapy product, Sponsors must ensure patients are closely monitored post-treatment. Implementing digital solutions to gather and analyze data may aid in collecting relevant clinical results.
To capture the serious acute and long-term side effects of cell and gene therapies, in-depth safety monitoring and timely signal detection are crucial for Sponsors as they develop any guidance and materials to manage these side effects.
GxP processing to assure that the treatment supplied meets regulatory requirements for patients
It’s important to note that developing a new cell and gene therapy product is a challenging process by nature. Thorough planning will ensure that the cell and gene therapy manufacturing is conducted as seamlessly as possible. Building and maintaining an effective Quality Management System (QMS) from early stage development and beyond will ensure patients can be treated with consistent, high quality products produced at qualified locations as well as that patient starting materials are handled in a GxP compliant and controlled way.
Other components for a licensed and fully operational cell and gene facility include equipment commissioning, qualification, and process validation. While process validation can present a challenge with orphan diseases and small patient sets, a matrix-based small sample set approach allows for bracketing of the patients and the treatments. This enables Sponsors to prove with a high degree of assurance that the process meets predetermined specifications in a no size fits all environment.
Creating a Decentralized Manufacturing Model, raw materials logistics, and scalable manufacturing
An opportunity in creating more accessible cell and gene therapies is the migration towards a decentralized manufacturing model, which can significantly reduce turn-around time while simultaneously cutting cold chain and logistics costs.
These manufacturing facilities must be scalable and able to flex with patient and therapy growth. Notably, decentralized manufacturers require auditing and inspection readiness support. Also, all raw material suppliers must account for auditing and inspection of sites prior to approval.
The increased flexibility of decentralizing the manufacturing model expands the geographical reach, and thus the number of patients likely to benefit while providing Sponsors with a more cost-efficient route.
Financial Hurdles and Reimbursement Management
The financial aspect of the development of Cell and Gene Therapy products presents a major challenge, mainly because the production costs are very high. Most of these costs come from the current manufacturing process, expensive raw materials, extensive supply chain, treatment characterization, comparability studies, and multitudes of tests to demonstrate safety, efficacy, and sterility. Sponsors should ensure that there is sufficient funding available when it is needed to achieve phase appropriate milestones.
Related to this is pricing and reimbursement management. Reimbursement relies on demonstrated clinical and economic benefits compared to already available therapies, something that is often difficult to prove in cell and gene therapies. High short-term costs combined with limited efficacy and effectiveness data creates uncertain cost-effectiveness.
Ideally after regulatory approval developers would achieve optimal price with maximum reimbursement for the approved target population. However, the reality is typically a trade-off between price and reimbursement level, target and selected patient population, and prescription and funding procedures.
Departing from the traditional approach of the legacy Clinical Research Organization (CRO) model, prioritizing research and strategic guidance, while also maintaining a comprehensive understanding of the challenges associated with CAGT development can help remove obstacles to ensure the successful development and launch of life-saving Cell and Gene Therapies.
Paula van Hennik
Paula got her PhD on the topic of haematopoietic stem cell assays (2001) at the Department of Haematology at the Erasmus University in Rotterdam, The Netherlands, conducted fundamental research on haematopoietic cell migration for about 11 years at Sanquin (i.e. Dutch Blood Transfusion Service) in Amsterdam, The Netherlands and has been working at the Dutch Medicines Evaluation Board since January 2012. Initially as clinical assessor with focus on oncology products. Since 1st of August 2016 she is alternate CHMP (Committee for Medicinal Products for Human Use) member representing the Netherlands with the oncology, haemato-oncology, part of the benign haematology and gyneacology products and contraceptives in her portfolio. She is also an observer at the Oncology Working Party at EMA (European Medicines Agency). At both the central and national level she is on a regular basis involved in interactions with HTA (Health Technology Assessment) bodies.
