Collaboration in Manufacturing is Key to Improving Patient Access for Gene Therapy and Cell Therapy

Betty Woo, PhD

Approximately 20 FDA-approved gene therapies and cell therapies are now available on the market, many of which reached commercialization just within the past few years. Meanwhile, across the globe, over 2,000 clinical trials evaluating gene therapy and cell therapy products are currently active. As such, the demand for these advanced therapies is expected to greatly increase over the coming years. Scaling up manufacturing and overcoming currently existing production bottlenecks is of critical importance in order to meet this growing demand.

Thermo Fisher Scientific held a panel entitled “Exploring Potential of AAV-Based Gene Therapy: Advances and Challenges” at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California. The panel, which was moderated by Betty Woo, PhD, the vice president and general manager of cell, gene, & advanced therapies at Thermo Fisher Scientific, included discussion of methods and technology for overcoming challenges that currently exist in the gene therapy manufacturing space. 

CGTLive™ reached out to Woo to learn more about the challenges that exist in gene therapy and cell therapy manufacturing and possible solutions. Woo discussed the growing demand for these potentially transformative therapies and emphasized the importance of cross-industry collaboration for ensuring greater patient access.

CGTLive: What are the biggest challenges or unmet needs that currently exist in the gene therapy manufacturing space?

Betty Woo, PhD: Cell and gene therapies are at a tipping point with imminent regulatory approvals that will expand access to these potentially curative therapies to larger patient populations, ranging from solid tumors to more prevalent and complex polygenic diseases. We anxiously await the first CRISPR-Cas9-based gene editing therapy for curing sickle cell disease this year. However, there are still challenges tied to the (ex vivo) genetic engineering and expansion of stem cells from a patient before reintroducing them back into the bone marrow of the same patient who has undergone a difficult precondition process. Nonetheless, this nonviral method for gene editing using CRISPR-Cas9 represents a significant advancement. Continued improvements in the precision, flexibility, and fidelity of gene editing offer tremendous potential for addressing even more complex genetic diseases.

More traditional viral vector approaches will remain at the forefront of gene therapy for the short/mid-term. Here, some of the challenges include scaling of viral vector manufacturing from lab-developed processes, including robust analytical methods required for safe and potent therapies. The most prevalent vector, adeno-associated virus (AAV) for in vivo applications, also represents an exciting opportunity and challenge, specifically regarding limitations in payload, targeting specificity, and potential for insertional mutagenesis.

What are some of the potential solutions to these challenges?

I allude to potential solutions above, including gene editing and delivery technologies, as well as technologies, methods, and processes required to scale AAV manufacturing. As an industry, we have largely migrated to suspension cultures and are working toward more standardized approaches to manufacturing to achieve optimal and consistent titers.

Lastly, there is a real opportunity here for cross-industry collaboration. By sharing in the wealth of knowledge currently available and forming meaningful partnerships, the gene therapy industry can come together to standardize development and manufacturing to reduce time-to-market for these groundbreaking drugs.

There are currently more than 2,000 active clinical trials for cell and gene therapies around the world. We are witnessing continued growth in this field, despite economic and funding headwinds. This presents imminent promise for patients with rare or orphan diseases, who have very few or no treatment options. Getting these treatments to patients faster remains a challenge, but there has been a push to streamline and scale up the manufacturing process.

One potential solution, and a focus of the ASGCT panel, is accelerating and optimizing the production of AAV vectors, which are used in about 82% of viral vector based gene therapies currently in development.

What should clinicians and the wider healthcare community know about the current state of gene therapy manufacturing?

Although gene therapy is still an emerging modality, with approximately 20 cell and gene therapies currently approved by the FDA, these therapies hold tremendous potential for large patient populations like Parkinson disease and Alzheimer disease, where there is high unmet need for effective treatments. It’s easy to see why going from no treatment options to having a potentially curative gene therapy will transform a patient’s quality of life. However, curative therapies have the potential to transform healthcare more broadly. Administered early in life, healthcare costs associated with doctors’ visits, medication, surgeries, hospital stays, and long-term care have profound economic impact on patients, payers, and healthcare systems. Fundamental imbalances are rapidly emerging in what we can manufacture versus the number of patients in need and what can be reimbursed upfront versus the long-term healthcare savings for these curative therapies.

More specifically, the healthcare community needs to understand that these incredible medicines can only reach patients if the industry can scale manufacturing effectively and at a cost that enables broad patient access. Patient access will be key over the next few years, and we will all have to work together to improve processes to make gene therapy viable and widespread as more and more therapies are approved. 

What important advancements do you see on the horizon in this space?

I’m excited over recent advancements in gene editing and delivery technologies, to improve our ability to target specific organs and reduce off-target effects, all while delivering a durable, effective treatment for patients.

As we learn from process analytical technology advancements in biologics manufacturing, I see even more potential in its application in cell and gene therapies where the identification and measurement of critical quality attributes is still at early stages. Ultimately through a combination of automation and analytical technologies, we are moving towards adaptive manufacturing aimed at increasing the quality and consistency of manufactured therapies.

When it comes to the advancement of cell and gene therapies, I can’t reiterate enough that collaboration is key to the field’s success. There are multiple risks tied to the scale-up of viral vector manufacturing and navigating the chemistry, manufacturing, and controls and regulatory requirements for clinical development. Entering critical collaborative partnerships can support, complement, and accelerate scale-up, whether that be in process support, technological expertise, business, or commercialization support. Figuring out how to maintain a level of flexibility is also key, as scientific discovery and technology development are always evolving. Collaborative partners can help accelerate time to market, develop a superior product, and ensure quality of supply and candidates’ advance in the clinic and eventually to commercial.

In a significant development earlier this year, Thermo Fisher and the University of California, San Francisco (UCSF), opened our current Good Manufacturing Practice-compliant cell therapy manufacturing facility at UCSF Medical Center’s Mission Bay Campus. Our collaboration was first announced in 2021 with the goal of expediting development, streamlining manufacturing, and improving patient access to cell-based therapies.

We look forward to continuing to collaborate across the cell and gene therapy space to help facilitate knowledge transfer, overcome industry obstacles, and accelerate time-to-market for these emerging therapies.

Transcript edited for clarity.

Click here for more coverage of ASGCT 2023.