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A rich clinical pipeline of regenerative medicine product candidates bodes well for a robust future.
Regenerative medicines encompass a range of emerging biotherapies, the most well-known of which are cell and gene therapies. Tissue therapies are also a category of regenerative medicines. The development of regenerative medicines has sparked some of the most innovative therapeutic targets and biomolecules. However, the complex nature of these medicines makes successful commercial development quite challenging. With significant leaps in drug development technologies over the past few years, where does the market for regenerative medicines stand today?
Much of the progress that regenerative medicines have made in the past two years would not have been possible without infusion of funds, and the investment patterns seen in 2021 are expected to strongly support the long-term growth and success of this sector. In the Alliance for Regenerative Medicine’s (ARM’s) 2022 state of the industry address (1), Janet Lambert, CEO of ARM, noted that the regenerative medicines sector, specifically cell and gene therapies, had another record-breaking year of investment in 2021. In particular, the rise of gene editing continued at a strong pace, which Lambert attributed to a hefty infusion of venture capital into early-stage companies.
According to Lambert in her state-of-the-industry presentation, 2021 set another investment record for cell, gene, and tissue-derived therapies, with $23.1 billion raised over the course of that year, reflecting a 16% increase from 2020. Lambert emphasized that gene therapy developers raised the most capital in 2021 with $10.6 billion raised, followed closely by cell-based immuno-oncology (cell IO) developers, with $10.1 billion raised. “Although gene therapy out-raised cell IO, cell IO continues to show the strongest growth with 26% increase in financings year-over-year,” Lambert said in the presentation.
Meanwhile, companies active in gene editing raised a total of $8.5 billion in 2021, which accounted for more than one-third of the total amount raised sector-wide, according to Lambert. A breakdown showed that companies active in gene editing made up $4.7 billion of the financing in the gene therapy category, or approximately 45% of the total gene therapy financings in 2021, up from 38% three years ago. “Excitement in this sub-sector is driven by the in-vivo CRISPR [clustered regularly interspaced short palindromic repeats] data from Intellia [Therapeutics]as well as the continuing advances in traditional and new editing technologies,” said Lambert. Meanwhile, products derived from base editing technology is set to enter the clinic in 2022, with the approval of the first gene-edited therapy potentially occurring in 2023, she noted in her presentation.
The year 2021 was notable for new regenerative medicine product approvals. With six new products approved, 2021 was the second best year on record, following the approvals of nine new regenerative medicines in 2016, stated Lambert in her state-of-the industry address. Additionally, 2021 was a notable year for approvals of cell-based immuno-oncology, with three new chimeric antigen receptor T cell (CAR T) therapies approved across the United States, Europe, and China, including the first approval of a B cell maturation antigen (BCMA)-targeted CAR T therapy, Abecma (idecabtagene vicleucel) by Celgene, a Bristol Myers Squibb company (2). Lambert noted that this product was also the first CAR T therapy approved for treating multiple myeloma.
Furthermore, 2021 also saw notable product approvals for regenerative medicine products for treating a serious inherited neurological disorder, a rare and historically fatal birth defect, and severe burns. 2021 was a breakout year for FDA’s regenerative medicine advanced therapy (RMAT) designation (3), in which three out of the four products approved in the UShad RMAT designation. “This designation, which ARM played a leading role in creating, was established in 2016 and is intended to expedite patient access to innovative regenerative medicine therapies. To date, 67 regenerative medicine programs have been awarded RMAT designation,” said Lambert her presentation.
ARM is currently tracking 2261 active global clinical trials in regenerative medicine, including both industry-sponsored trials and academic and government-sponsored trials. Lambert presented clinical trial data in her state-of-the-industry address, which represents data from the third quarter of 2021 (end-of-year clinical data not yet reported at the time Lambert’s state-of-the-industry was given). Looking at specific indications, cancer is shown as the number one target for cell and gene therapies, with 1354 ongoing trials in cancer indications. There is also significant clinical development activity in other disease categories, namely neurological disorders, diabetes and diabetes-related disorders, cardiovascular, rare genetic disease, and stroke, according to ARM’s findings.
“Of these [2261 active global clinical trials in regenerative medicine], there are 1129 active industry-sponsored regenerative medicine trials globally,” said Lambert. Cell-based immuno-oncology makes up the largest portion of the regenerative medicine clinical trial landscape, which is primarily due to a large number of Phase I trials in immuno-oncology indications. According to data collected by ARM, cell-based immuno-oncology makes up more than half of all Phase I industry-sponsored regenerative medicine trials, which reflects a relatively recent tilt towards the immuno-oncology field. With 143 Phase III industry-sponsored trials currently underway, 44% are in cell therapy, 33% are in gene therapy, and 22% are in immuno-oncology, according to ARM.
“We’re also tracking 1100 academic and government-sponsored trials worldwide, about the same number as industry trials. As a whole, these trials, not surprisingly, tend to be earlier stage with a significantly different technology mix. In academia, we also see a much larger proportion of cell therapy trials and a much lower proportion of gene therapy trials,” explained Lambert in her address.
Based on a rich pipeline, ARM anticipates that 2022 may be a record year of approvals for new gene therapies targeting rare diseases. “It could be a really active year, with as many as 15 anticipated decisions across the US and Europe, including nine on never-before approved products,” Lambert emphasized in her state-of-the-industry address. “As of now, we’re due to have regulatory decisions on five new products across the US and Europe from BioMarin Pharmaceutical, Gencyte Therapeutics, PTC Therapeutics, uniQure and CSL Behring, and Crystal-Bio. We will very likely see a record number of approvals for this product class in 2022.”
Looking at the clinical pipeline for regenerative medicines beyond 2022, Lambert expects that the industry will gradually see an evolution from rare monogenic diseases and liquid tumors to more prevalent diseases and solid tumor cancers. “We have many late-stage programs in a variety of cancers. Importantly, the first gene therapy for a prevalent disease could be just a few years out. The oft quoted 2019 FDA prediction of 10–20 approvals by the year 2025 still looks doable, albeit likely at the lower end of that range. This is something [FDA] has recently reinforced in conversations with us,” Lambert stated in her presentation.
1. ARM, “Cell & Gene State of the Industry Briefing,” alliancerm.org, Jan. 10, 2022.
2. FDA, “FDA Approves First Cell-Based Gene Therapy for Adult Patients with Multiple Myeloma,” Press Release, Mar. 27, 2021.
3. FDA, “Regenerative Medicine Advanced Therapy Designation,” FDA.gov, accessed Jan. 21, 2022.
Feliza Mirasol is the science editor for BioPharm International.
Vol. 35, No. 2
When referring to this article, please cite it as F. Mirasol, “Gaining Ground: The Rise of Regenerative Medicines,” BioPharm International 35 (2) 16–17 (2022).