Perspectives: Hold on Tight for the Ride

May 31, 2023 / by Jeff Briganti

A crazy, mixed-up world of cell & gene therapy in 2023

News concerning cell and gene therapy (CGT) may make you feel like you are on a rollercoaster. The ride moves very quickly with a lot of ups and downs, plus a few unexpected turns. As we move through 2023, excitement for CGT remains high, but there are lingering concerns about manufacturing and the ability of health care systems to keep up with the science.

The coaster climbs…
According to Timothy Hunt, CEO of the Alliance for Regenerative Medicine, 13 new cell and gene therapies could be approved in the US, Europe, or both by the end of 2023. In addition, there are more than 2,000 on-going clinical trials, with 200 in Phase III. Early data suggests that only 14% of CGT therapies will progress from phase II through approval, much lower than the 43% success rate with small molecule drugs. However, this still translates into many more approvals in the years to come.

At the micro-level, the picture is just as bright, with promising results or approvals coming rapidly. Here are just a few examples:

• At the American Association for Cancer Research (AACR) annual meeting, researchers at NYU Langone Health’s Perlmutter Cancer Center presented results of a phase IIb trial with an experimental mRNA vaccine combined with an immunotherapy. The addition, the mRNA vaccine reduced recurrence or death from melanoma by 44% compared to the immunotherapy alone
• Allogene’s phase I trial of an “off-the-shelf” CAR T-cell therapy for metastatic clear cell renal demonstrated encouraging antitumor activity and a manageable safety profile. A single administration of ALLO-316 could be an effective treatment for patients with CD70+ solid tumors and hematologic malignancies
• The FDA has approved Omisirge (omidubicel-onlv), an allogeneic cord blood-based cell therapy that reduces the risk of infection after a stem cell transplant in patients with blood cancers.

…and it dips
Despite the positivity surrounding the science, the CGT market is experiencing significant challenges. After record investments in 2020 and 2021, financing has reverted to pre-pandemic levels. A portion of the increased investment was certainly pandemic-specific research and development but that likely doesn’t explain the entire decline.

Increasing interest rates and a challenging economy is also impacting available funds. The immediate, real-world impact of tight funding is evident in the first quarter of 2023 when 56 biopharmas laid off staff compared to 30 companies in the same period in 2022, an 87% increase.

And then come the curves
Despite five years of collective experience, manufacturing hurdles for autologous CAR-T therapies remains a struggle for some of the first approved protocols. Though as many as five CAR-T products have been approved for third- or fourth-line therapies for different indications, wait times remain unacceptable. These patients are given hope based on the success of the therapies, but then are put on a waiting list that “goes out to six months,” according to Elizabeth Budde, M.D., Ph.D, who chairs City of Hope’s clinical cellular immunotherapy committee.

The delay is not limited to autologous therapies. Long timelines and capacity constraints are easing but remain a concern across the industry. In addition, therapies in the clinical trial pipeline are for more common indications, meaning future success will require even more manufacturing capacity. McKinsey & Company comments, “Large contract development and manufacturing organizations have invested heavily in this space, with a number of large acquisitions in the past few years. While exciting, this rapid influx of money and new technology have not yet solved the bottlenecks and challenges…”

Perhaps the biggest curve yet to be addressed is patient access. Regulatory agencies, particularly in the US and Europe, are taking positive steps to modernize regulatory frameworks to address these newer technologies. However, payment systems are not equipped to ensure patients have access to these life-altering therapies. This is particularly challenging in Europe, across a broad range of payment systems by country.

Slowing and leveling the rollercoaster
As a trusted contract manufacturing partner, Aldevron is helping to slow and level out the rollercoaster by:

• Doubling the space dedicated to mRNA products at our Breakthrough Campus
• Increasing recombinant proteins and enzymes capacity and capabilities at our Madison Innovate Campus
• Implementing the Danaher Business System (DBS), a continuous improvement program

Focusing on what we do best, delivering high-quality plasmid DNA, RNA, and protein for cell and gene therapy applications, allows us to make the improvements necessary to grow with the market. The roller coaster will keep rolling. We’re here to ride it with you.

• Learn about our expanded mRNA capabilities, including our drug product offering
• Have questions about this topic? Contact Jeff Briganti
• Have an idea for a topic? Let us know!