FDA Activity Recap: March 2024 Features 2 Major Approvals, ODAC Meeting, and More
Catch up on any of the key FDA news stories you may have missed last month, with coverage highlights from the CGTLive® team.
Last month, March 2024, the CGTLive® team was diligently tracking the FDA's activities related to the development of cell and gene therapies for the treatment of rare, complex, and otherwise challenging diseases and disorders.
The agency has continued to ramp up its activities around these therapies as more of them progress through the pipeline in tandem. Last month proved no different, with a major approval in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) and in metachromatic leukodystrophy (MLD), an Oncologic Drugs Advisory Committee (ODAC) Meeting related to potential expanded approvals in 2 chimeric antigen receptor T-cell (CAR-T) therapies, and a few smaller actions. Our team has highlighted these below.
Click the read more buttons for more details and information about each update.
FDA Approves Liso-Cel (Breyanzi) as First CAR-T for CLL, SLL
March 15, 2024 — The FDA has approved Bristol Myers Squibb’s CAR T-cell therapy lisocabtagene maraleucel (liso-cel; Breyanzi) for treating adults with relapsed or refractory CLL or SLL who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor, under the accelerated approval pathway.
The approval marks the first CAR T-cell therapy approved for treating CLL or SLL. Breyanzi was previously approved for the second-line treatment of relapsed or refractory large B-cell lymphoma (LBCL) in the US, Japan, and Europe, and for relapsed and refractory LBCL after 2 or more lines of systemic therapy in Japan, Europe, Switzerland, and Canada.
Liso-cel is an autologous CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain designed to enhance the expansion and persistence of the CAR T cells. It will be delivered to patients with CLL or SLL in a one-time infusion with a single dose containing 90 to 110 x 106 CAR-positive viable T cells.
FDA Approves Orchard Therapeutics’ Gene-Edited Cell Therapy Arsa-Cel for Metachromatic Leukodystrophy
March 18, 2024 — The FDA has approved Orchard Therapeutics’ gene-edited cell therapy atidarsagene autotemcel (arsa-cel, previously referred to as OTL-200 and now marketed in the US under the name Lenmeldy), for the treatment of children with presymptomatic (PS) late infantile (LI), PS early juvenile (EJ), or early symptomatic (ES) early juvenile (EJ) metachromatic leukodystrophy (MLD). It is the first gene therapy for children with MLD to be approved in the United States.
The FDA’s decision was based on data from patients treated with arsa-cel across 2 clinical trials (NCT01560182; NCT03392987) and additional patients treated in expanded access frameworks. These patients had follow-up times ranging from 0.64 years to 12.19 years (median, 6.76).
“This is the first FDA-approved treatment option for children who have this rare genetic disease,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research (CBER), said in a statement. “We remain committed to advancing scientific and regulatory principles that enable the efficient development and review of safe, effective and innovative products that have the potential to change patients’ lives.”
ODAC Meeting: Cilta-Cel Gets Unanimous Vote, Ide-Cel Wins Majority Vote for Benefit-Risk Profile
March 15, 2024 — The FDA’s ODAC Meeting has unanimously voted (11 yes, 0 no, 0 abstain) in favor of ciltacabtagene autoleucel's (cilta-cel; Janssen, Legend Biotech) benefit-risk profile for patients with relapsed and lenalidomide-refractory multiple myeloma (MM) after at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent.
ODAC also voted in favor of idecabtagene vicleucel's (ide-cel; Bristol Myers Squibb, 2seventybio) sBLA for patients with triple-class exposed relapsed or refractory (r/r) MM, with 8 yes votes, 3 no votes, and 0 abstains.
"I felt that the lack of the tail of the curve for PFS and the lack of effects on OS outweighed the benefits and led me to conclude that it is not better to get ide-cel now versus later," Neil Vasan, MD, PhD, Assistant Professor of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University, said about his "no" vote on ide-cel.
FDA Deems Mesoblast’s Data on Remestemcel-L Cell Therapy Sufficient for BLA Submission in Pediatric SR-aGVHD
March 26, 2024 — The FDA has informed Mesoblast that the available data from the phase 3 MSB-GVHD001 clinical trial (NCT02336230) is sufficient for the submission of a biologics license application (BLA) for its allogeneic mesenchymal stromal cell therapy, remestemcel-L, for the treatment of children with steroid-refractory acute graft versus host disease (SR-aGVHD).
The company noted that it plans to submit the BLA in the second quarter of 2024. Mesoblast stated it will attempt to address the remaining product characterization issues prior to the submission.
“We thank the agency for their collaborative approach,” Silviu Itescu, MBBS, FRACP, the chief executive officer of Mesoblast, said in a statement. “The responses and guidance from FDA are clear and provide us with a high level of confidence to refile our BLA for remestemcel-L in children with SR-aGVHD.”
FDA's CBER Hosts Webinar on CAR-T Guidance Document
March 12, 2024 — The FDA's CBER hosted a webinar highlighting key points from the final version of the CAR-T guidance document on March 7, 2024. In the webinar, a recording of which is now available on the FDA's website, the speakers covered the main points from the general, CMC, nonclinical, and clinical considerations for CAR-T development from the document. The webinar also included a question-and-answer segment (which begins about 30 minutes into the presentation).
"We first posted the draft guidance on considerations for the development of CAR T-cell products in March of 2022..." Kim Schultz, PhD, the division director of Division 2 for the Office of Gene Therapy CMC, said at the beginning of the webinar. "We received over 650 comments from approximately 85 stakeholders, and we really appreciate your thoughtful insights into where more clarity would be helpful. After consideration of each comment and with revisions as needed, the final guidance was then published at the beginning of 2024."
Schultz and colleagues offered a review of the guidance and responded to several questions, including those about the advantages of vector copy number reporting, essential studies required for investigational new drug applications, considerations for the development of CAR-T products for pediatric conditions, recommendations for dose-finding studies, the controlling of donor variability, animal model needs, and many more.
