State of the industry
At the Alliance for Regenerative Medicine’s (ARM’s) annual industry briefing (1), Tim Hunt, CEO of ARM, characterized the CGT field as “now-maturing”. The CGT space is achieving a new normal categorized by serial approvals of breakthrough products according to Hunt in his state-of-the-industry address.
The biopharma industry has gone from seeing five gene therapy products approved within the span of five years (2017–2022) to witnessing breakthrough approvals for five gene therapies in just one year, 2023. According to Hunt, ARM was hopeful that the industry would get approval for five gene therapies for rare disorders approved within a single year, “and we called it our 5x5x5” (1).
“We got that one right: five programs approved in one year,” Hunt emphasized in his address. Importantly, the 2023 gene therapy approvals were for five programs in rare diseases that had been difficult to treat until now: one program in dystrophic epidermolysis bullosa, one in Duchenne muscular dystrophy, one in hemophilia A, and two in sickle cell disease (Table I).
“I think [this is] a glimpse of a lot of the progress we’ll see in the future,” said Hunt in his address.
Rich development pipeline
ARM’s industry evaluation shows that, across North America, Europe, and Asia Pacific in 2023, the field of CGTs saw more than 2500 developers throw their hat into the ring and nearly 2000 clinical trials underway. Investment into this sector was nearly $12 billion for the year, which Hunt noted in the industry briefing as being slightly down compared to 2022, but that commitment to the development of CGTs remains vibrant. Hunt went on to explain that there is significant time, talent, and money being committed to CGTs with the goal of getting these therapies to patients with debilitating, often fatal, diseases or disorders (1).
Looking ahead to 2024, Hunt noted that ARM sees a total of 17 programs that could, in theory, get approval in the year. “We’re not going to get all 17, let’s be clear,” he stated in his address, “but we’ll get a subset of that. [However,] there’s 17 things that we can identify at this point that are at least in the discussion.”
Regulatory outlook
In ARM’s estimation, the regulatory outlook for 2024 includes seven total decisions on CGT approvals pending—five in the United States and two in the European Union (EU)—and five total submissions pending—three in the US and two in the EU (1). Meanwhile, the number of regulatory submissions possible in 2024 come to five in total, three in the US and two in the EU. “We’re optimistic that we’ll see a lot of these get pulled through to the finish line,” Hunt stated. “It is also possible that we could see five more gene therapies approved in the United States for rare genetic conditions.”
Hunt also emphasized potential milestones that the industry may see in 2024. Among these are the first ever approval of an adoptive cell therapy for solid tumors in the US, and the first US approval of an allogeneic T-cell therapy. The industry can also potentially see additional therapies approved to treat hemophilia A, hemophilia B, and dystrophic epidermolysis bullosa, following the recent approval success of CGTs in these conditions in 2023 and 2022 (Table I).
“I think that’s the sign of an increasingly maturing field, right where you see more competition, which ultimately is good news for patients. If you go back in time to 2019 when FDA … said we could see 10 to upwards of 20 approvals a year starting in 2025, we think that is tracking rather nicely for that time period. It’s conceivable that we could see that [level of approvals] in the US in 2024 but we’d have to almost essentially run the tables,” said Hunt (1).
Nevertheless, there has been a significant amount of progress in this field, Hunt also noted. With success, however, comes further challenges, he continued. Pricing pressure for innovative therapeutics remains a volatile situation in the US market but, by Hunt’s assessment, the CGT market is still in its early days and working through the business model. “The good news is healthcare systems have worked through this before. They’re adapting right now, I would argue, led by the commercial payers, and we will work through these challenges yet again,” Hunt remarked in his address (1).
Future goals
Meanwhile, a key goal for ARM in 2024 and 2025 is to discuss value and society and how these new therapies are perceived. ARM will do this through a new framework it is calling the Gene Therapy for Patients and Societies (GPS) framework. The GPS framework will have five components centered around the value of gene therapies, which:
- target devastating, often deadly diseases
- target significantly expensive diseases
- are highly effective
- often save healthcare systems money
- are affordable (even before taking into account cost offsets).
Because gene therapies are affordable—even before taking into account cost offsets—Hunt posited that this component would make gene therapies easily digestible for healthcare systems in the years ahead.
What’s more, Hunt pointed out that US healthcare systems are modernizing, which is beneficial for CGTs. The Center for Medicare and Medicaid Innovation’s (CMMI’s) access model, the CMMI Cell and Gene Therapy Access Model, adopted in February 2023 (11), for example, is intended to establish a voluntary partnership among the Centers for Medicare & Medicaid Services (CMS), state Medicaid agencies, and biotech companies. From these partnerships, outcomes-based agreements (OBAs) can be set up and administered, which can particularly help smaller states in the US that lack the resources to administer OBAs, according to Hunt. The model is projected to launch in 2025.
“We think this is a great development,” stated Hunt. “We believe this will be beneficial, especially to smaller Medicaid agencies that will just frankly struggle to put together the infrastructure to measure and partner with companies.” Furthermore, moving forward with this CMMI access model will be a way to modernize how the US healthcare system pays for CGTs (1).
Meanwhile, FDA has also been modernizing to prepare for an anticipated wave of CGTs to hit the market. In 2023, the agency established the Office of Therapeutic Products (OTP), a new “super office” structure that was transitioned from the former Office of Tissues and Advanced Therapies (OTAT). OTP was implemented on Feb. 26, 2023 (12). Hunt praised this transition, stating that it was “a very welcome move.”
“We are doing a lot to partner with FDA over the [p]ast year and a half to try to accelerate cell and gene therapy development and manufacturing,” Hunt emphasized in his address (1). In preparing for the future, ARM and FDA will be looking at streamlining CGT development and
manufacturing, collaborating on complex chemistry, manufacturing, and controls issues, improving societal readiness for CGTs, and scanning the horizon for future technologies.
References
1. ARM. Cell & Gene State of the Industry Briefing. alliancerm.org/arm-event/sotibriefing, Jan. 8, 2024.
2. FDA. FDA Approves Omidubicel to Reduce Time to Neutrophil Recovery and Infection in Patients with Hematologic Malignancies. Press Release, April 17, 2023.
3. FDA. FDA Approves First Topical Gene Therapy for Treatment of Wounds in Patients with Dystrophic Epidermolysis Bullosa. Press Release, May 19, 2023.
4. FDA. FDA Approves First Gene Therapy for Treatment of Certain Patients with Duchenne Muscular Dystrophy. Press Release, June 22, 2023.
5. FDA. FDA Approves First Cellular Therapy to Treat Patients with Type 1 Diabetes. Press Release, June 28,2023.
6. FDA. FDA Approves First Gene Therapy for Adults with Severe Hemophilia A. Press Release, June 29, 2023.
7. FDA. FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. Press Release, Dec. 8, 2023.
8. EMA. Hemgenix. ema.europa.eu/en/medicines/human/EPAR/hemgenix (accessed Jan. 11, 2024).
9. uniQure. uniQure Announces License Agreement with CSL Behring to Commercialize Hemophilia B Gene Therapy. Press Release, June 24,2020.
10. FDA. FDA Approves First Gene Therapy to Treat Adults with Hemophilia B. Press Release, Nov. 22, 2022.
11. CMS. HHS Secretary Responds to the President’s Executive Order on Drug Prices. Press Release, Feb. 14, 2023.
12. FDA. Establishment of the Office of Therapeutic Products. fda.gov (accessed Jan. 11, 2024).
About the author
Feliza Mirasol is the science editor for BioPharm International.
Article Details
BioPharm International
Volume 37, No. 2
February 2024
Pages: 7–9
Citation
When referring to this article, please cite it as Mirasol, F. Bracing for a Future Wave of Advanced Therapies. BioPharm International 2024, 37 (2), 7–9.