ASGCT 2024 Comes at Pivotal Time for Gene and Cell Therapy Sector

Baltimore Skyline_Taylor Tieden

Pictured: Baltimore skyline with color treatment/Taylor Tieden for BioSpace

A record 8,000 attendees are expected at this week’s 27th Annual Meeting of the American Society of Gene & Cell Therapy in Baltimore to discuss the opportunities and challenges facing the industry. Billed as the largest gathering of gene and cell therapy professionals, ASGCT 2024 starts tomorrow and will run through the end of the week, bringing together stakeholders from therapeutic developers and investors to patient advocates, policymakers and regulators.

I, along with Managing Editor Jef Akst, will be on-site, aiming to assess where the field stands now and what near- and longer-term breakthrough technologies are on the horizon. And I have to say, I’m excited. These relatively new modalities have taken biopharma by storm and continue to dominate the news with clinical results demonstrating breakthrough potential in a range of indications and FDA efforts to accommodate the anticipated flood of regulatory applications, as well as safety concerns and manufacturing challenges.

ASGCT President Jeffrey Chamberlain told BioSpace that the annual meeting will have a record 2,000 abstracts this year on a variety of topics.

“This is going to be the largest meeting we’ve ever had,” Chamberlain said. “There are an increasing number of approved therapies and this really gives us a chance to highlight all of those.” He added that there are more than 20 gene therapies that have been approved worldwide—half of those in the United States—and more than 60 cell therapies approved globally with many of those in the U.S.

FDA’s View of Cell and Gene Therapies Is Evolving

On the regulatory front, 2023 was a banner year for cell and gene therapies (CGTs), with seven approvals in the U.S. and one in the European Union. And all signs point to 2024 surpassing last year. This year, the FDA has given the green light to four new CGTs and has several upcoming PDUFA dates for other novel therapies.

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, will be speaking in two sessions at ASGCT 2024.

On Wednesday morning, Marks will be featured in a fireside chat on regulating CGTs, hosted by Kristin Van Goor, executive director and U.S. head of global regulatory policy and innovation at Takeda Pharmaceuticals. As the FDA’s top biologics regulator, Marks has been an advocate for regulatory flexibility with regard to CGTs for rare diseases.

Van Goor told BioSpace that she and Marks will discuss “all the hot topics from IND to BLA.” Specifically, she continued, “I plan to front-load questions on areas of rapidly evolving policy and precedent.”

Marks will also participate in a Thursday morning fireside chat on global regulatory convergence that includes officials from the Brazilian Health Regulatory Agency and Japan’s Pharmaceuticals and Medical Devices Agency. Marks has previously argued that disparate CGT requirements among different countries—from preclinical tests to manufacturing—make it difficult for patients in certain areas of the world to have access to therapies, particularly for rare diseases.

Basic Science, Translational Research

Beyond clinical and regulatory affairs, Chamberlain said ASGCT 2024’s agenda will also highlight pivotal basic science and genetics—including translational studies—and the researchers who are making breakthroughs.

“We’re going to have some really exciting talks on what’s coming out of the basic science laboratories, what’s moving into more advanced translational work and what is close to clinical trials,” Chamberlain said. “We’re going to really span the whole spectrum.”

In a keynote address on Wednesday morning, Kevin Campbell, director of the Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center at the University of Iowa’s Carver College of Medicine, will speak about the mechanism of muscular dystrophies and development of therapeutic strategies to restore muscle function. 

Campbell has “led the way for years” in understanding the mechanisms underlying several muscular dystrophies, Chamberlain said, and will talk “about the interaction between basic science and the development of gene therapies.”

Another point of discussion will be the Bespoke Gene Therapy Consortium (BGTC), a public-private collaboration between the National Institutes of Health, the FDA, industry and patient groups to help accelerate the delivery of gene therapies for rare diseases. BGTC’s primary goal is to improve understanding of the basic biology of adeno-associated virus (AAV) vectors to optimize bioproduction technologies and increase their therapeutic efficacy.

While AAV vectors are one of the safest platforms and most common tools for gene delivery, there are challenges in producing sufficient quantity and quality of such gene therapy products. An AAV manufacturing workshop will be held Tuesday morning at ASGCT 2024 providing an overview of how early process development decisions (pre-Phase I), including the basics of chemistry, manufacturing, and controls (CMC) considerations for gene therapies, can translate into clinical success.

“There’s a couple of presentations at the meeting this year on new vector technologies. You know, getting away from the same old ones that most people are using,” Chamberlain said. “I think that’s going to be really important—to develop new vectors. And there are a number of exciting talks [at ASGCT 2024] and I think breakthroughs that we’re going to be hearing about in the next year in developing nonviral delivery systems.”

In December 2023, the FDA approved the first gene therapies for sickle cell disease, including the first-ever CRISPR therapy. Gene, epigenetic and RNA editing will also be a big part of the agenda at ASGCT 2024 with several sessions focused on CRISPR technology, as well as the need for greater progress in making in vivo genome editing scalable to treat a lot more patients.

CGT Challenges, Opportunities

ASGCT 2024 comes at a pivotal time for the sector. In January 2024, the FDA pushed for a class-wide boxed warning on all commercial BCMA-directed and CD19-directed CAR T cell immunotherapies due to the “risk of T cell malignancies, with serious outcomes, including hospitalization and death.”  The agency continues to investigate 22 reported cases of T cell malignancies in patients who received CAR-T therapies.

“Anytime you hear reports of adverse events or things that are unanticipated it’s a concern we need to pay attention to,” Chamberlain said. “But the number of incidences appears to be quite low . . . you have to look at risk versus benefit.”

Indeed, the safety concerns have not deterred oncologists, drug developers or investors, and Chamberlain noted that ASGCT 2024 received a “very large number of abstracts” for this year’s annual meeting on the development of CAR T cell therapies. He said there is also work on CAR NK cells. CAR T-cell therapies have become a game changer for some patients with blood cancer. Now, Chamberlain said, “People are trying to adapt . . . CAR technologies more towards solid organs.”

Meanwhile, Sarepta’s Elevidys has faced scrutiny not for safety concerns but for questionable efficacy. In a controversial regulatory decision in June 2023, the FDA granted accelerated approval to the gene therapy as the first for Duchenne muscular dystrophy (DMD), despite Elevidys having missed the primary functional endpoint. The regulator’s decision was based on data showing it increased expression of the micro-dystrophin protein, a biomarker the agency determined is “reasonably likely to predict clinical benefit” in DMD patients four to five years of age.

Four months after the approval, however, Elevidys failed a confirmatory trial. Still, Sarepta is persisting with its application seeking full approval and an expanded label for the therapy. The FDA has set a PDUFA date of June 21.

“Sarepta did a fantastic job in figuring out how to scale this up and start to apply it effectively in the clinic—and you know, we’re seeing a lot of progress,” commented Chamberlain, whose lab at the University of Washington designed a micro-dystrophin that Sarepta’s approved therapy uses. “One of the things that we’ve seen is some of the kids that are being treated with this new therapy are doing tremendously well. Unfortunately, others are not doing quite as well, and we’re still trying to get a handle on that.”

Greg Slabodkin is the news editor at BioSpace. You can reach him at Follow him on LinkedIn.     

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