By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1
Cell & Gene’s sister publication and fellow Life Science Connect resource, Life Science Leader magazine, is the essential business journal for life science executives who work for everything from emerging biotechs to Big Pharmas, aka you. Life Science Leader’s annual Industry Outlook issue hits mailboxes the first week of December, and in it, I contributed an article about the future of commercial manufacturing featuring commentary from Chris Fox, President at Novartis Gene Therapies; Karen Kozarsky, Ph.D., Founder & CSO at SwanBio Therapeutics; and Vaishali Shukla, VP, Quality Commercial Manufacturing at Kite Pharma. We didn’t have room in the issue for all the valuable information they shared, so here’s what didn’t make it to print. And by the way, do you already receive Life Science Leader? Be sure to subscribe to the magazine and bookmark lifescienceleader.com, as Chief Editor Ben Comer and his team cover the cell and gene sector frequently.
From a commercial manufacturing standpoint, list and explain the things that went well in 2022. Can these things be replicated in 2023 and beyond? Why or why not?
Shukla: As the personalized medicine industry grows and new modalities are introduced, there is increasing demand to manufacture a greater number of complex therapeutics while still maintaining the high standard of quality that patients deserve. As early pioneers in the field of cell therapy, Kite has been heavily involved in helping set the industry standards for commercial manufacturing for cell therapies. Manufacturing quality, reliability, and speed are critically important in CAR T-cell therapy, and our patients and physicians count on Kite’s 96% success rate in manufacturing CAR T cells. As demand for our CAR T-cell therapies has grown rapidly, we have invested significantly in added manufacturing capacity.
2022 was an important year for Kite. Earlier this year, we received U.S. FDA approval to start commercial production at our new CAR T-cell therapy manufacturing facility in Frederick, Maryland. This site joins our existing manufacturing facilities in the LA area and in Amsterdam, Netherlands to form a dedicated in-house cell therapy manufacturing network, spanning process development, vector manufacturing, clinical trial production, and commercial product manufacturing. This network, combined with a variety of optimization efforts, allows.
We’re committed to continuing to find ways to optimize and maintain the high standard of our commercial manufacturing speed, reliability, and quality as demand for CAR T-cell therapy grows. For instance, our median U.S. production time today, from apheresis to product release is industry leading. In the U.S., it’s 16 days, and in Europe it is 19 days, and that includes the transportation logistics to get the cells to us, yet we are still working to continuously improve, finding ways to reduce that turnaround even more.
Regarding commercial manufacturing for genetically engineered t-cell therapies, what remain the sector’s top challenges?
Shukla: CAR T-cell therapy is individually made for each patient from their own T-cells, and it is the ultimate ‘custom product’ where each batch represents product for one patient. Given this, getting the manufacturing process right and consistent is critical, as is being able to scale up to deliver for thousands of patients. With the autologous nature of these products, there are many steps between collection of a patients’ cells and administration of CAR T-cell therapy that need to be implemented. We are constantly monitoring our supply chain process to keep up with complex logistics and ensure sufficient materials and capacity to meet the high demand for these life-saving therapies.
The cost and clinical infrastructure required to deliver gene therapies is a major challenge to providing treatment to individuals in under-resourced areas. What are your thoughts on how to improve access?
Fox: Gene therapies like Zolgensma provide incredible innovation, but they also fundamentally challenge a healthcare system built around chronic treatment. From a pricing standpoint, we believe that the price of a medicine should reflect the real value it brings, and we believe gene therapies bring tremendous benefit to patients, their families, and the healthcare system overall. However, they raise new questions on how to ensure equitable access.
These access challenges cannot be solved by one party alone. Harmonization with governments, and across key stakeholders, is a critical component that can lower local barriers and support quality patient care. This approach is a major component of Novartis’ access principles, and it has served us well – we are very proud of challenges we have been able to overcome to achieve approval for Zolgensma in 43 countries and access pathways in 32 countries to date. For those countries without formal pathways, compassionate use and accelerated access programs can bridge the gap for families in need. For instance, our global Managed Access Program (gMAP) for Zolgensma is available to eligible patients with SMA under the age of two in countries where Zolgensma has not received regulatory approval or formal access approval. The program was refined after launch to prioritize patients who do not have access to treatment alternatives to focus the program on patients with the greatest need.
Our job – and the industry’s job at large – will continue to be balancing the system needs and challenges with the very real needs that patients have.
Regarding gene therapies for the spinal cord, list and explain the things that went well in 2022. Can these things be replicated in 2023 and beyond? Why or why not?
Kozarsky: It seems like every year in gene therapy is an exciting year with the incredible advancements that take place. Having said that, it never feels like enough when it comes to progress. One thing that sticks out in my mind this year was the success of Novartis’ Zolgensma for spinal muscular atrophy. It is used as a one-time infusion into a vein. It provides a new copy of the gene that makes the human SMN protein. From what I’ve read, 2,300 babies have been treated so far worldwide. These babies are so severely affected, they don’t even sit up, and most die between two and four years of age. Using this as a gene replacement therapy, the children are achieving milestones and living longer.
In terms of replication, although Novartis is developing the therapy, it was originally developed by a small startup much like Swan. They are demonstrating that innovations can come from a multitude of places and have impact. In terms of the science, this program helps de-risk other approaches like ours because they are using the same type of AAV we are using. The target tissue, spinal cord, is being reached paving the way for other iterative science. Many others can build on lessons they have learned.
The other company getting a lot of attention is Taysha Gene Therapies, developing a gene therapy for giant axonal neuropathy (GAN) with the same target. Both therapies are well established in clinical trials for efficacy and safety and have orphan drug designation.