The COVID-19 pandemic continued to disrupt lives across the globe in 2021, but that didn’t keep the cell and gene therapy industry from advancing. With many new regulatory approvals anticipated in 2022, the industry shows no signs of slowing down.
‘A breakout year for RMAT designation’
Six new products were approved in the United States, the European Union or China in 2021. These included three CAR-T therapies, one gene therapy and two tissue therapies.
Three of the four therapies approved in the U.S. had the Food and Drug Administration’s (FDA) Regenerative Medicine Advanced Therapy (RMAT) designation. The approval of Abecma, a CAR-T therapy from bluebird bio and Bristol Myers Squibb (BMS) to treat multiple myeloma, marked the first approval of a therapy with RMAT designation.
During the Alliance for Regenerative Medicine’s (ARM) Cell and Gene State of the Industry Briefing in January 2022, CEO Janet Lambert called 2021 “a breakout year for the FDA’s RMAT designation.” Since established in 2016, she said 67 programs have been awarded RMAT designation to date.
CAR-T therapy as an earlier line of treatment?
In February 2021, Breyanzi from BMS became the third FDA-approved autologous CAR-T therapy to treat adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. While significant, it was study information released later in the year that has the potential to change the standard of care.
BMS and Kite, a Gilead company, announced results of separate studies of Breyanzi and Yescarta® as second-line therapies. The companies each compared their respective CAR-T to second-line treatment standard of care (chemotherapy plus autologous hematopoietic stem cell transplant) for adults with relapsed or refractory large B-cell lymphoma. Both companies reported superior outcomes to standard of care.
Notably, Kite’s study, ZUMA-7 began in 2017 and had a median follow-up of more than two years. Compared to standard of care, patients who received Yescarta demonstrated significantly better event-free survival than standard of care. While not yet approved by regulatory agencies for earlier use, regulatory filings are underway with global agencies, including the FDA.
During the ARM Cell and Gene State of the Industry Briefing, Emile Nuwaysir, PhD, who is the CEO of Ensoma, Chairman of ARM, and Chairman of BlueRock Therapeutics, said that with the safety advances in the field, CAR-T’s show promise for even earlier use.
“We have learned to handle the safety of these incredibly potent medicines. We’ve learned how to utilize a living cell as a medicine. And that type of learning applies to all the cells that follow to the entire field of immuno-oncology. It’s very exciting, and this would lead a reasonable scientist to conclude that very soon CAR-Ts will be a first-line therapy,” he said.
Gene therapies targeting rare disease are in the spotlight
A number of regulatory decisions for cell and gene therapies are expected in the U.S. and EU in 2022 and 2023. Speaking on a panel during the ARM Cell and Gene State of the Industry Briefing, Jason Cole, Chief Business Officer, bluebird bio, said he thinks 2022 will be a “watershed year” for the gene therapy field.
“Pioneers in the space really started the revolution of what these kind of genetic medicines can be. And now we are really starting to see that pay off for patients and for our health care system and I think that’s just super exciting,” he said.
Gene therapies for rare diseases are among those with filed or planned biologics license applications (BLAs) or market authorization applications (MAAs) in 2022 or 2023. That includes hematopoietic stem cell gene therapies from Orchard Therapeutics for metachromatic leukodystrophy (MLD) in the U.S. and Wiskott-Aldrich syndrome in the EU.
Orchard’s gene therapy for early-onset MLD received approval in the EU in late 2020. In 2021, Be The Match BioTherapies® announced an expansion of our multi-year partnership with Orchard to provide supply chain services in support of the therapy’s commercial launch in the EU.
Will momentum continue for allogeneic cell therapies?
While autologous CAR-T therapies are showing promise as an earlier line of treatment, the nature of these autologous therapies can limit access. Creating an individual product for every patient takes time and for some patients, cell collection may not be possible.
That’s led many cell therapy developers to pursue allogeneic options that could be available “off-the-shelf” with continued allogeneic cell therapy growth expected in 2022. While allogeneic CAR-Ts, CAR-NKs and other therapies are in early stages of development, Atara Biotherapeutics presented efficacy and safety results from an allogeneic T-cell immunotherapy Phase III trial during the ASH Annual Meeting in December 2021.
The therapy, tabelecleucel (tab-cel®), treats Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD) after hematopoietic cell transplant or solid organ transplant. In November 2021, the company announced the EMA validated its MMA. They anticipate an approval decision in the second half of 2022.
Be The Match BioTherapies has been a strategic supplier to Atara since 2016 providing the HLA-specific cellular starting material to support Atara’s tabelecleucel program and its other pipeline candidates. In January 2022, we announced a multi-year partnership extension with Atara.
While challenges certainly existed in 2021, the cell and gene therapy industry continued to thrive and make advancements for patients. With thousands of cell and gene therapy clinical trials underway, we look forward to what the future brings.
Other articles that may interest you:
Overcoming roadblocks along the cell therapy product pathway (lifescienceleader.com)
Alleviating CGT bottlenecks: Standards needed to ensure volumes, quality of starting material (biopharma-reporter.com)
Lessons in life or death logistics (pharmaceuticalprocessingworld.com)