The 3rd quarter of 2024 brought one accelerated approval and one missed PDUFA action date.
On August 1, 2024, Adaptimmune received accelerated approval of Telcelra (afamitresgene autoleucel) for treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared Companion Diagnostic devices. Tecelra is the first TCR product approved by FDA and the second cell-based therapy for a solid tumor (after Iovance’s Amtagvi was approved for metastatic melanoma in February 2024).
The action date for Humacyte’s acellular tissue engineered vessel (ATEV™) product was August 9, 2024 (adjusted from Saturday August 10, 2024). Humacyte released a statement on August 9 that FDA had informed the company that additional time was needed for review. The press release further stated that “FDA leadership expressed an apology for their inability to complete the review by the PDUFA date, and currently we do not yet have a revised action date.”
Further in the past...
The 2nd quarter of 2024 brought mixed news for pending CGT BLA submissions.
On April 25, 2024, Pfizer received approval for Beqvez (fidanacogene elaparvovec) for treatment of adults with mild to moderate hemophilia B.
On June 20, 2024, Sarepta received approval of Elevdys (delandistrogene moxeparvovec) for ambulatory patients who have a confirmed mutation in the DMD gene and accelerated approval for non-ambulatory patients and have a confirmed mutation in the DMD gene.
Two pending BLAs received Complete Response Letters (CRL) from FDA. Abeona Therapeutics announced on April 22nd that FDA issued a CRL for prademagene zamikeracel (pz-cel) for treatment of recessive dystrophic epidermolysis bullosa (RDEB). The press release notes that “CMC requests in the CRL pertain to validation requirements for certain manufacturing and release testing methods, including some that were captured in the observations during the FDA’s pre-license inspection (PLI).” Abeona notes that no additional clinical efficacy or clinical safety were requested by FDA to support approval.
Rocket Pharmaceuticals announced receipt of a CRL on June 28, for their product marnetegragene autotemcel for severe Leukocyte Adhesion Deficiency-I (LAD-I). The company’s press release stated that FDA requested limited additional chemistry, manufacturing, and controls (CMC) information. The CRL followed a 3-month clock extension from the original action due date after submission of additional CMC information.
**This indication is approved under accelerated approval based on overall response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
List does not include HPC, Cord Blood products for use in unrelated donor hematopoietic progenitor cell transplantation procedures.
List also does not include previously approved products that are no longer being marketed.
The following information on BLAs currently under US FDA review was obtained from company press releases.
No upcoming meetings of the Cellular, Tissue, and Gene Therapies Advisory committee for CGT topics have been announced.
Upcoming workshop:
Workshop on Integration Site Analysis During Long Term Follow-Up for Gene Therapies with Integrating Viral Vectors
November 14, 2024
Recent past:
Advancing Rare Disease Therapies Through an FDA Rare Disease Innovation Hub
October 16, 2024-recording not yet available
OTP Town Hall: Cell Therapy CMC Readiness for Late-Stage INDs
September 5, 2024- recording available
FDA Public Workshop on Best Practices for Meeting Management
July 22, 2024- recording and event materials available
The following links to past Meeting Materials include access to the recorded video link, transcript, or slides.
OTP Town Hall: CMC Readiness for Gene Therapy BLAs
June 4, 2024
Nonclinical Assessment of Cell and Gene Therapy Products
August 30, 2023
Decentralized Clinical Trials
June 20, 2023
Regulatory Education for Industry (REdI) Annual Conference 2023
June 5-9, 2023
OTP Town Hall: Cell Therapy Chemistry, Manufacturing, and Controls – June 2023
June 8, 2023
OTP Town Hall: Gene Therapy Chemistry, Manufacturing, and Controls – April 2023
April 25, 2023
Methods and Approaches for Capturing Post-Approval Safety and Efficacy Data on Cell and Gene Therapy Products
April 27, 2023
Clinical Trials: The Patient Experience
April 13, 2023
FDA CBER Office of Therapeutic Products (OTP) Advanced Manufacturing and Analytical Technologies (AMAT) for Regenerative Medicine Therapies (RMT) Workshop
March 14, 2023
OTAT Town Hall: Clinical Development of Gene Therapy Products for Rare Diseases
February 7, 2023
Assessing Genetic Heterogeneity in the Context of Genome Editing Off-Targets in Gene Therapy Products
December 16, 2022
OTAT Town Hall: Cell Therapy Chemistry, Manufacturing, and Controls
December 7, 2022
FDA/PQRI Workshop on the Regulatory Framework for Distributed and Point of Care Pharmaceutical Manufacturing: An Opportunity for DM/POC Stakeholder Engagement
November 14 - 16, 2022
FDA CBER OTAT Patient-Focused Drug Development Listening Meeting — Patient Perspectives on Gene Therapy Products
November 15, 2022
Natural History Studies to Support Regenerative Medicine: A How-To Webinar
October 27, 2022
OTAT Town Hall: Gene Therapy Chemistry, Manufacturing, and Controls
September 29, 2022
2022 Center for Biologics Evaluation and Research (CBER) Science Symposium
September 20-22, 2022
Regulatory Education for Industry (REdI) Annual Conference 2022
June 6 - 10, 2022
Annual Patient Engagement & Regenerative Medicine Meeting 2022: An FDA CBER Workshop for Patient Advocates
May 24, 2022
RegenMedEd Webinar: The Critical Role of Patients in Advancing Gene Therapy Treatments for Rare Diseases
March 9, 2022
CBER updated the list of guidances that CBER intends to publish in the remainder of calendar year 2024. Those specifically relating to CGT products are:
1. Frequently Asked Questions — Cell and Gene Therapy Products; Draft Guidance for Industry
2. Accelerated Approval of Human Gene Therapy Products for Rare Diseases; Draft Guidance for Industry
3. Recommendations for Determining Eligibility of Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) and multiple supporting guidances focusing on specific communicable disease agents.
Conducting Clinical Trials With Decentralized Elements September 2024
Purpose and Content of Use-Related Risk Analyses for Drugs, Biological Products, and Combination Products July 2024
Draft, comment period closed 9/9/24
Platform Technology Designation Program for Drug Development May 2024
Read Kim Benton's article regarding this guidance here.
Safety Testing of Human Allogeneic Cells Expanded for Use in Cell-Based Medical Products; Draft Guidance for Industry
Read Amanda Mack and Alicja Fiedorowicz's publication regarding this guidance here.
Considerations for the Use of Human-and Animal-Derived Materials in the Manufacture of Cell and Gene Therapy and Tissue-Engineered Medical Products; Draft Guidance for Industry April 2024
Read Blake Bergam and Sara Mills' article on this subject here.
Providing Regulatory Submissions in Electronic Format: IND Safety Reports Guidance for Industry April 2024
Real-World Evidence: Considerations Regarding Non-Interventional Studies for Drug and Biological Products March 2024
Early Alzheimer’s Disease: Developing Drugs for Treatment March 2024
Q14 Analytical Procedure Development Q2 March 2024
(R2) Validation of Analytical Procedures March 2024
Advanced Manufacturing Technologies Designation Program February 2024
Human Gene Therapy Products Incorporating Human Genome Editing January 2024
Potency Assurance for Cellular and Gene Therapy Products; Draft Guidance for Industry December 2023
Master Protocols for Drug and Biological Product Development December 2023
Rare Diseases: Considerations for the Development of Drugs and Biological Products December 2023
Data Standards for Drug and Biological Product Submissions Containing Real-World Data December 2023
Translation of Good Laboratory Practice Study Reports: Questions and Answer November 2023
Submitting Clinical Trial Datasets and Documentation for Clinical Outcome Assessments Using Item Response Theory November 2023
Submitting Patient-Reported Outcome Data in Cancer Clinical Trials November 2023
Guidance for Industry: Voluntary Consensus Standards Recognitions Program for Regenerative Medicine Therapies October 2023
Guidance for Industry: Voluntary Consensus Standards Recognitions Program for Regenerative Medicine TherapiesData Standards for Drug and Biological Product Submissions Containing Real-World Data October 2023
Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities October 2023
Our first Regulatory Roundup LIVE was our Unbridled Excellence #4 and featured our unparalleled team of former FDA regulators discussing the latest and greatest regulatory news...that's DHC Master Principal Kimberly Benton and Master Practice Expert Don Fink, as well as Senior Principal Heath Coats, former Dark Horse Kevin Whittlese, and Senior Practice Expert Tal Salz. Go to the main Unbridled Excellence page to watch/download episode #4 on demand.