Advancing medicine through cell and gene therapy

Scientific and operational strategies for CGT success

The journey from scientific discovery to commercial success in cell and gene therapy is no small feat. The complexities of disease biology, clinical trials and patient engagement all play critical roles.

There are four key aspects essential to advancing CGT: disease biology understanding, therapeutic potential, clinical trial readiness and early patient engagement, Srivastava explained, emphasizing the importance of understanding the biology behind the disease and the therapeutic potential of CGT in addressing unmet medical needs.

Srivastava added that clinical trial readiness is a relatively new challenge for CGT. Unlike traditional treatments, these therapies are difficult to deliver and require infrastructure capable of supporting intricate clinical trial designs.

"Clinical trial readiness is a new aspect," he said. These therapies are difficult to deliver, and the infrastructure must be viable.

Companies need to plan for the logistics of these trials early, making sure that infrastructure and capabilities are in place before trials begin.

One of the most critical factors for CGT success is patient engagement. As Srivastava pointed out, engaging patients early on and understanding the natural history of the disease can significantly influence trial design and outcomes. Patient advocacy groups, too, play a pivotal role in shaping the clinical trial process. Vnook agreed, highlighting that patient engagement is the core driver of successful CGT development.

"All this time, money and effort is spent, from the creation of a small cell in a lab to the approval stage, and patient engagement is essential to ensure these therapies reach the people who need them," Vnook explained.

Scaling and manufacturing

One of the most significant operational challenges in cell and gene therapy is scaling up manufacturing. Unlike small molecule drugs, which are relatively straightforward to produce, CGT products are living therapies that must be manufactured at a much larger scale without sacrificing quality. Vnook highlighted the importance of planning for scalability and regulatory standards early on.

Vnook also stressed the importance of considering alternatives, such as different cryopreservation technologies or logistics methods, to avoid delaying product launches. Neglecting these logistics early on can result in costly delays in commercialization.

Sethi added that technological advancements, particularly in cell processing, enhance scalability. Innovations like automated bioreactors, closed-system bioprocessing and advanced cell culture techniques are streamlining the manufacturing process, improving efficiency and reducing the potential for error.

The environment for culturing cells outside the body must be controlled to mimic the body's natural controls, which is where advancements in bioreactors come in.

Despite these advancements, Sethi cautioned that adoption remains slow. Companies often focus on getting their products approved first and worry about manufacturing later, which is a mistake that can hinder scalability down the road, he explained.

"It may be necessary to start thinking about manufacturing earlier rather than prioritizing speed, running through the regulatory process, and then having to revisit and change it later. This approach can lead to time-consuming comparison studies," Sethi underscored.

Navigating global markets

Expanding into global markets presents additional challenges for CGT, especially regarding financial and regulatory hurdles that may result in a funding gap.

De Kalbermatten refers to this funding gap as "Death Valley, a phase where companies can become stalled due to insufficient capital," highlighting the substantial investment needed to advance a therapy from early-stage development to market.

Moving from phase 2 to phase 3 clinical trials requires a massive influx of resources, and many companies struggle to secure the necessary funding.

Vnook pointed out that harmonizing clinical trials across regions can help companies streamline approval processes. However, differences in regulatory requirements between regions, such as using dimethyl sulfoxide in Japan versus the United States, can complicate matters.

Each region has its own regulatory requirements, which must be considered early in the process to avoid costly setbacks, Vnook advised. She also emphasized the importance of early planning for market expansion. Ensuring trials meet global regulatory standards can save time and resources down the line.

Another significant issue is investors' reluctance to fund manufacturing automation early in the process. De Kalbermatten shared how investors often push companies to prioritize clinical trials and regulatory approval over manufacturing. However, this approach can create inefficiencies later on, delaying commercialization efforts and increasing costs.

Investors want to see clinical trial results before they fund manufacturing, but delaying automation only creates more problems later, de Kalbermatten warned.

Supply chain complexities in CGT

The supply chain for CGT is uniquely challenging due to the fragile nature of the therapies and the specialized logistics required to ensure their viability. Srivastava explained that cell and gene therapies often require transporting the patient to the therapy rather than delivering the therapy to the patient, which is a major shift from traditional drug distribution models.

Srivastava explained that this places enormous demands on supply chain logistics, especially around cold-chain management.

Another major concern is ensuring that all partners in the supply chain -- from couriers to distributors -- are well-coordinated to prevent any disruption in therapy delivery. These are living therapies, and a delay in shipment could mean the difference between life and death, Srivastava noted. He emphasized the importance of investing in digital infrastructure early on to ensure seamless coordination between all supply chain partners.

Sethi emphasized the importance of de-risking supply chains, noting that companies must collaborate with reliable suppliers and ensure their systems are validated for the specific needs of CGTs. Stable suppliers of raw materials and critical technologies are essential to the manufacturing process.

Expanding patient access and engagement

A key theme throughout the panel was the importance of patient access and engagement. Vnook stressed that despite the complexity of CGTs, communication with patients must remain simple and clear.

Healthcare providers' jobs are to communicate the treatment and its benefits in a way that patients can understand, even during times of distress. There is a strong need for patient education and clear messaging, particularly when explaining cell and gene therapies to those unfamiliar with these new treatments, Vnook added.

De Kalbermatten echoed this sentiment but acknowledged that expanding access to underserved markets remains a significant challenge. "It's difficult to propagate CGT in underserved markets due to the high cost of production and the lack of infrastructure," he said.

However, he was optimistic that technological advancements and improved economies of scale could help make these therapies more accessible in the future.

Sethi proposed that governments could play a larger role in expanding access. Increased government involvement and support are necessary to reach more patients, especially in underserved markets. Governments can help bring stakeholders together to ensure that therapies are accessible to a broader patient population.

Although the future of CGT holds immense promise, the road ahead is filled with challenges. As this panel discussion illustrated, the CGT community must navigate complex regulatory landscapes, scale production, and ensure that patients are engaged and informed throughout the therapy process.

As the industry works to overcome these challenges, collaboration between scientists, manufacturers, regulatory bodies and patients will ensure that CGT reaches its full potential in revolutionizing healthcare.

Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.