Stephen Majors from the Alliance for Regenerative Medicine, which hosts the conference, spoke with BioSpace about what the more than 2,000 attendees can expect to learn next week in Phoenix about the pressing issues confronting the industry.
The 2024 Cell & Gene Meeting on the Mesa has a new location this year—held Oct. 7–9 in Phoenix, having moved from Carlsbad, Calif. Despite the change in venue, the industry continues to face the same regulatory, manufacturing and commercialization challenges as the sector hits an inflection point.
BioSpace will provide on-site coverage of the three-day event, where more than 2,000 attendees will get an update from key stakeholders on the industry’s progress and the stumbling blocks that are impeding the advancement of cell and gene therapies (CGTs).
One of the biggest business challenges for the sector is the investment headwinds that have continued this year, according to the Alliance for Regenerative Medicine (ARM), the Washington, DC–based advocacy organization that represents the industry and hosts the annual Meeting on the Mesa.
Stephen Majors, global head of communications at ARM, told BioSpace that capital markets “have been really tough” the past few years for CGT. “There’s a lot of companies in the space pursuing a smaller amount of money,” he observed.
“Inflation projections were, of course, a driver of this because the gene therapy companies tend to be the furthest away from commercialization and therefore inflation concerns hit them hardest,” Majors said. “We’re hopeful that with the reduction of interest rates and a better inflation outlook going forward, we’ll start to see more money flow into the sector.”
Manufacturing, Commercialization Hurdles
Majors said that manufacturing is also a major challenge for the industry due to a lack of standardization and the fact that scale-up has often been an obstacle to regulatory approval and commercialization.
“There are still some manufacturing challenges and the ability to produce these therapies at scale at the demand that they’re needed. That’s something that the sector’s still working through,” according to Majors.
A Government Accountability Office report last year found that while regenerative medicine technologies—including gene therapies, cell therapies and tissue-engineered products—are highly promising, they are being held back by the lack of widely accepted standards and guidelines to govern their use, development and manufacture.
Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research (CBER), provided a sobering assessment in May at the 2024 American Society of Gene & Cell Therapy conference about the opportunities and challenges facing the CGT industry. He said that while it’s “an exciting time” for gene therapies in particular—including the approval of competing therapies for sickle cell disease—there are “some real challenges” including manufacturing, clinical development timelines and different global regulatory requirements.
After their groundbreaking approvals in late 2023, infusions of Vertex-CRISPR Therapeutics’ and bluebird bio’s sickle cell gene therapies have recently begun, offering hope to patients and the companies, which are looking to jumpstart revenues.
“Those of us who have been watching this for a while were always expecting these launches to be kind of slow with steady uptick over time, because of the length of time involved in the identification of eligible patients and in the consultation process they have with their doctors about whether this is the right therapy for them,” Majors said.
A panel session at Meeting on the Mesa on commercializing cell and gene therapies in today’s “dynamic market” environment will be a “hot” session given other recent product launches, according to Majors. He expects “some lessons learned from that, maybe some wisdom and advice for launches yet to come.”
For the second year at the conference, ARM CEO Tim Hunt will lead a session on the importance of ethics in cell and gene therapies. Majors said it is meant to be a broad-based look at several issues, including “the pricing and value” of CGT, global access such as “how long it will be” before therapies reach patients in developing and low- and middle-income countries, and ultra-rare diseases in which the sizes of patient populations “fall outside what usually works from a commercialization perspective.”
According to market research and consulting firm Nova One Advisor, the global CGT market was valued at more than $18.1 billion in 2023 and is expected to reach approximately $97.3 billion by 2033.
While CGT developers face challenges along several key stages of the product life cycle, the firm notes that “key success factors such as enabling patient access, managing supply chain and manufacturing operations, evidencing compliance with increasingly complex regulatory requirements and alternate business models impose a greater burden” for CGTs than for chemical-based pharmaceuticals.
Regulatory Environment Takes Center Stage
On the regulatory front at Meeting on the Mesa, the conference will hear from Nicole Verdun, director of the FDA’s Office of Therapeutic Products within CBER. According to Majors, Verdun will “give us an update on where the FDA is in terms of how they’re looking at cell and gene therapies, their staffing levels to ramp up with the submissions,” as well as accelerated approvals and “other details about the regulatory frameworks they’re looking at” for CGT.
Scott Gottlieb, former FDA commissioner, will participate in a fireside chat at the conference. In 2019, as the head of the agency, Gottlieb predicted that the regulator would be approving 10 to 20 cell and gene therapy products annually by 2025. Early next year, his bookThe Miracle Century: Making Sense of the Cell Therapy Revolution is slated to be published. In it, he “tackles the issues that must be addressed to enable wide adoption of these treatments,” according to the publisher’s description.
Majors said that Gottlieb will provide Meeting on the Mesa with an overview of “where we are in the field right now” and “what we can expect over the next few years.”
“Historically, we haven’t seen much of a difference between the U.S. and Europe in approvals,” according to Majors. “There were a handful of gene therapies that got approved in Europe first before they got approved here. But what we’re seeing more recently is the U.S. starting to have more approvals.”
ARM in its annual Cell & Gene State of the Industry Briefing in January predicted that the sector could see up to 17 regulatory approvals in the U.S. and European Union this year. However, Majors in an update to BioSpace said the organization has cut its forecast a bit and is now predicting up to 14 approvals, with eight in the U.S.—including the FDA’s first approval in March for an autologous gene therapy from Orchard Therapeutics to treat the rare metabolic disease metachromatic leukodystrophy in children, and the FDA nod in April for Pfizer’s hemophilia B gene therapy Beqvez.
“If we looked at last year as kind of the breakthrough year of gene therapy, which it certainly was, this year we’re seeing a lot of advances in cell therapy,” Majors said. “There’s been a number of really impressive fundraises from cell therapy companies. There’s been a lot of excitement and progress in autoimmune diseases. And there’s been expansion of CAR T therapies into earlier lines of treatment.”
In February, the FDA granted approval to Iovance Biotherapeutics’ lifileucel as the first one-time cell therapy for a solid tumor and the first tumor-infiltrating lymphocytes therapy. In April, the regulator greenlit two CAR T cell therapies for the earlier treatment of multiple myeloma—BMS and 2seventy Bio’s Abecma, and J&J and Legend Biotech’s Carvykti. And in August, Adaptimmune Therapeutics’ Tecelra became the first FDA-approved engineered cell therapy for solid tumors and the first new synovial sarcoma therapy in more than a decade.
Majors sees Autolus Therapeutics’ FDA application for its next-generation CAR T therapy obe-cel in relapsed/refractory adult acute lymphoblastic leukemia as an important milestone, with a PDUFA target action date of Nov. 16. According to Autolus, obe-cel is a CD19 CAR T cell investigational therapy designed to overcome the limitations in clinical activity and safety compared to current CD19 CAR T cell therapies.
The FDA in January pushed for a class-wide boxed warning on all commercial BCMA- and CD19-directed CAR T cell immunotherapies due to the “risk of T cell malignancies, with serious outcomes, including hospitalization and death.”
“There was correlation but there wasn’t necessarily causation,” Majors said about the regulator’s findings on CAR T therapies and secondary cancers, noting that “the benefits of these therapies continue to outweigh the risks” providing an “important tool at the disposal of physicians for patients with serious, aggressive forms of cancer.”
