In the first half of 2023 we’ve seen FDA approval of 5* novel cell and gene therapy products. All are the first of a kind in one or more ways. Omisirge is the first modified cord blood derived product approved by the FDA. Vyjuvek is the first HSV vector, first gene therapy for dystrophic epidermolysis bullosa, and first topically administered gene therapy. Elevidys is the first gene therapy for DMD. Lantrida is the first cell therapy* for treatment of type 1 diabetes. Roctavian is the first gene therapy for hemophilia A.
With 5 additional BLAs under review with FDA Action Due Dates in the second half of the year (see table below for details), 2023 promises to continue to be an exciting year for cell and gene therapy!
In this quarter's Regulatory Roundup, we'll summarize BLA approvals to date, CGT BLAs under US FDA Review (forthcoming in 2023), Recent FDA Guidance Documents, Draft FDA Guidance open for public comment, Rules & Legislation, an upcoming OTP Town Hall, and Past FDA Workshop and Town Halls.
On April 17, 2023, FDA approved Omisirge for intravenous use in adults and pediatric patients 12 years and older with hematologic malignancies who are planned for umbilical cord blood transplantation following myeloablative conditioning to reduce the time to neutrophil recovery and the incidence of infection. Omisirge is derived from allogeneic cord blood, which is processed and cultured with nicotinamide (a form of vitamin B3). Omisirge dosage contains a cultured and a non-cultured fraction which include specifications for minimum percentage CD3+ and CD34+ cells. Omisirge is the first modified cord blood derived product approved by the FDA.
The application received Priority Review, Breakthrough Therapy, and Orphan designations.
Link to FDA approval documents: OMISIRGE
On May 18, 2023, FDA approved Vyjuvek for the treatment of wounds in patients 6 months of age and older with dystrophic epidermolysis bullosa (DEB) with mutation(s) in the collagen type VII alpha 1 chain (COL7A1) gene.
Vyjuvek is a replication deficient herpes simplex virus type 1 (HSV-1) genetically modified to express the human type VII collagen (COL7) protein. Vyjuvek is mixed with the supplied sterile excipient gel for topical application to fragile, blistering skin wounds. There are important novel aspects, or “firsts” with this BLA approval: replication deficient HSV-1, gene therapy for dystrophic epidermolysis bullosa (DEB), topical administration, and health care providers can administer the Vyjuvek at a healthcare professional setting (e.g., clinic) or at the patient’s home, which is an important option for DEB patients.
The application received Fast Track, Regenerative Medicine Advanced Therapy, Priority Review, and Orphan Drug designations, and a Rare Pediatric Disease Priority Review Voucher.
Link to FDA approval documents: VYJUVEK
On June 22, 2023, FDA granted accelerated approval of Elevidys to Sarepta Therapeutics, Inc. Elevidys is indicated for the treatment of ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene. This indication is approved under accelerated approval based on expression of ELEVIDYS micro-dystrophin. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Elevidys is a non-replicating, recombinant, adeno-associated virus serotype rh74 (AAVrh74) based vector containing the Elevidys micro-dystrophin transgene under the control of the MHCK7 promoter. The micro-dystrophin protein expressed by Elevidys is a shortened version (138 kDa, compared to 427 kDa size of dystrophin expressed in normal muscle cells) that contains selected domains of dystrophin expressed in normal muscle cells.
Elevidys is the first gene therapy for DMD. This application received a Rare Pediatric Disease Priority Review Voucher.
Link to FDA approval documents: ELEVIDYS
On June 28, 2023, FDA approved Lantidra for the treatment of adults with type 1 diabetes who are unable to approach target glycated hemoglobin (average blood glucose levels) because of current repeated episodes of severe hypoglycemia (low blood sugar) despite intensive diabetes management and education. Lantidra is allogeneic islets of Langerhans derived from a deceased donor pancreas. Islets contain several types of endocrine (hormone-secreting) cells, including β-, α-, pancreatic peptide- (PP-), δ-, and ε-cells.
Lantrida is the first cell therapy* for treatment of type 1 diabetes.
Link to FDA approval documents: LANTIDRA (donislecel)
On June 29, 2023, FDA approved Roctavian for the treatment of adults with severe hemophilia A without pre-existing antibodies to adeno-associated virus serotype 5 detected by an FDA-approved test. Roctavian is a non-replicating, recombinant adeno-associated virus (AAV) serotype 5 -based vector containing a DNA sequence encoding the B-domain deleted SQ form of the human coagulation factor VIII (hFVIII-SQ).
Roctavian is the first gene therapy for hemophilia A. The application received Orphan, Breakthrough Therapy, Regenerative Medicine Advanced Therapy, and Priority Review designations.
Link to FDA approval documents: ROCTAVIAN
The following information on BLAs under US FDA review (five more forthcoming in 2023 and two scheduled out into 2024) was obtained from company press releases.
Q9(R1) Quality Risk Management
Decentralized Clinical Trials for Drugs, Biological Products, and Devices
Assessing User Fees Under the Prescription Drug User Fee Amendments of 2022
S12 NONCLINICAL BIODISTRIBUTION CONSIDERATIONS FOR GENE THERAPY PRODUCTS
A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers
Drug-Drug Interaction Assessment for Therapeutic Proteins; Guidance for Industry
E6(R3) GOOD CLINICAL PRACTICE (GCP)
Submit Comments by 09/05/2023
Generally Accepted Scientific Knowledge in Applications for Drug and Biological Products: Nonclinical Information
Submit Comments by 07/24/2023
Acute Radiation Syndrome: Developing Drugs for Prevention and Treatment
Submit Comments by 07/19/2023
Pediatric Drug Development: Regulatory Considerations — Complying With the Pediatric Research Equity Act and Qualifying for Pediatric Exclusivity Under the Best Pharmaceuticals for Children Act; Draft Guidance for Industry
Submit Comments by 07/17/2023
Pediatric Drug Development Under the Pediatric Research Equity Act and the Best Pharmaceuticals for Children Act: Scientific Considerations
Submit Comments by 07/17/2023
Pediatric Drug Development: Regulatory Considerations — Complying With the Pediatric Research Equity Act and Qualifying for Pediatric Exclusivity Under the Best Pharmaceuticals for Children Act
Submit Comments by 07/17/2023
E6(R3) GOOD CLINICAL PRACTICE (GCP)
Submit Comments by 09/05/2023
Generally Accepted Scientific Knowledge in Applications for Drug and Biological Products: Nonclinical Information
Submit Comments by 07/24/2023
Acute Radiation Syndrome: Developing Drugs for Prevention and Treatment
Submit Comments by 07/19/2023
Pediatric Drug Development: Regulatory Considerations — Complying With the Pediatric Research Equity Act and Qualifying for Pediatric Exclusivity Under the Best Pharmaceuticals for Children Act; Draft Guidance for Industry
Submit Comments by 07/17/2023
Pediatric Drug Development Under the Pediatric Research Equity Act and the Best Pharmaceuticals for Children Act: Scientific Considerations
Submit Comments by 07/17/2023
Pediatric Drug Development: Regulatory Considerations — Complying With the Pediatric Research Equity Act and Qualifying for Pediatric Exclusivity Under the Best Pharmaceuticals for Children Act
Submit Comments by 07/17/2023
E6(R3) GOOD CLINICAL PRACTICE (GCP)
Submit Comments by 09/05/2023
Generally Accepted Scientific Knowledge in Applications for Drug and Biological Products: Nonclinical Information
Submit Comments by 07/24/2023
Acute Radiation Syndrome: Developing Drugs for Prevention and Treatment
Submit Comments by 07/19/2023
Pediatric Drug Development: Regulatory Considerations — Complying With the Pediatric Research Equity Act and Qualifying for Pediatric Exclusivity Under the Best Pharmaceuticals for Children Act; Draft Guidance for Industry
Submit Comments by 07/17/2023
Pediatric Drug Development Under the Pediatric Research Equity Act and the Best Pharmaceuticals for Children Act: Scientific Considerations
Submit Comments by 07/17/2023
Pediatric Drug Development: Regulatory Considerations — Complying With the Pediatric Research Equity Act and Qualifying for Pediatric Exclusivity Under the Best Pharmaceuticals for Children Act
Submit Comments by 07/17/2023
Following a proposed order issued in October 2021, FDA will move forward with exempting certain categories of biological products from the CARES Act shortage reporting requirements. The two categories of products the agency is exempting are blood and blood components for transfusion, as well as cell and gene therapy products, where a single lot treats one patient.
Nonclinical Assessment of Cell and Gene Therapy Products
The following links to the Meeting Materials include access to the recorded video link, transcript, or slides.
* Lantrida is not included in CEO Anthony Davies' Straight from the Horse's Mouth article entitled Cell and Gene Therapy has Come of Age (7/10/2023) because there is a strict definition of cell therapy by which this therapy would not be included. Please see the ** footnote in that article.
