Regulatory Roundup - Dark Horse Consulting Group

Stay current with the latest updates in US FDA news from our team of Regulatory experts.

BLA review updates

FDA CBER’s Office of Therapeutic Products approved 3 BLAs in the 3^rd quarter of 2025, and thoughts will vary on whether they call should be considered CGT or unique BLAs. On December 9, 2025, Fondazione Telethon ETS received approval for Waskyra (etuvetidigene autotemcel) for Wiskott-Aldrich syndrome. Waskyra is indicated for pediatric patients six months and older and adults with WAS who have a mutation in the WAS gene and for whom hematopoietic stem cell transplantation (HSCT) is appropriate and no suitable human leukocyte antigen (HLA)-matched related stem cell donor is available. This is a first approved cell and gene therapy product from a non-profit applicant.
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Axogen, Inc.’s Avance (acellular nerve allograft-arwx) received accelerated approval on December 3, 2025. Avance is acellular nerve scaffold for the treatment of adult and pediatric patients aged 1 month or older with sensory, mixed, and motor peripheral nerve discontinuities.
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Novartis Gene Therapies, Inc. received approval for Itvisma (onasemnogene abeparvovec-brve) on November 24, 2025 for the treatment of spinal muscular atrophy (SMA) in adult and pediatric patients 2 years of age and older with confirmed mutation in survival motor neuron 1 (SMN1) gene. Itvisma has the same active ingredient as Zolgensma. Zolgensma is administered as a single intravenous infusion with weight-based dosing. In contrast, Itvisma is a twofold-concentrated formulation of the same drug substance, and is administered as a fixed dose independent of patient weight, directly to the central nervous system via a single intrathecal injection.
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2026 started with the news of a Complete Response Letter issued to Pierre Fabre for tabelecleucel on January 9, 2025. Tabelecleucel is intended to treat Epstein-Barr virus–positive post-transplant lymphoproliferative disease (EBV+ PTLD) after failure of standard-of-care therapy.

US FDA CGT Approvals to date

Product

Company

Indication

Date of Initial Approval

WASKYRA
etuvetidigene autotemcel

Fondazione Telethon ETS

for pediatric patients six months and older and adults with Wiskott-Aldrich syndrome who have a mutation in the WAS gene and for whom hematopoietic stem cell transplantation (HSCT) is appropriate and no suitable human leukocyte antigen (HLA)-matched related stem cell donor is available

12/9/2025

AVANCE
acellular nerve allograft-arwx

Axogen, Inc

treatment of adult and pediatric patients aged 1 month or older with sensory, mixed, and motor peripheral nerve discontinuities**

12/3/2025

ITVISMA
onasemnogene abeparvovec-brve

Novartis Gene Therapies, Inc.

treatment of spinal muscular atrophy (SMA) in adult and pediatric patients 2 years of age and older with confirmed mutation in survival motor neuron 1 (SMN1) gene

11/24/25

PAPZIMEOS

Precigen, Inc

Treament of adults with recurrent respiratory papillomatosis

8/14/25

ZEVASKYN

Abeona Therapeutics

recessive dystrophic epidermolysis bullosa (RDEB)

04/28/2025

ENCELTO

Neurotech Pharmaceuticals, Inc.

Treatment of adults with idiopathic macular telangiectasia type 2

03/07/2025

SYMVESS

Humacyte Global, Inc.

For use in adults as a vascular conduit for extremity arterial injury when urgent revascularization is needed to avoid imminent limb loss, and autologous vein graft is not feasible.

12/19/2024

RYONCIL

Mesoblast, Inc.

For treatment of steroid-refractory acute graft-versus-host disease (SR-aGVHD) in pediatric patients 2 months of age and older.

12/18/2024

REGENECYTE

StemCyte Inc.

For use in unrelated donor hematopoietic progenitor cell transplantation procedures in conjunction with an appropriate preparative regimen for hematopoietic and immunologic reconstitution in patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment.

11/20/2024

KEBILIDI

PTC Therapeutics

Accelerated approval for treatment of adult and pediatric patients with aromatic L-amino acid decarboxylase (AADC) deficiency.

11/13/2024

AUCATZYL

Autolus Limited

For treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

11/8/2024

TELCELRA

Adaptimmmune

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).

8/1/2024

ELEVYDIS

Sarepta Therapeutics Inc.

treatment of Duchenne muscular dystrophy (DMD) in patients who are ambulatory and have a confirmed mutation in the DMD gene
treatment of DMD in patients who are non-ambulatory and have a confirmed mutation in the DMD gene **

6/20/2024

BEQVEZ

Pfizer, Inc

For the treatment of adults with moderate to severe hemophilia B (congenital factor IX deficiency) who:

Currently use factor IX prophylaxis therapy, or
Have current or historical life-threatening hemorrhage, or
Have repeated, serious spontaneous bleeding episodes, and,
Do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid as detected by an FDA-approved test

4/25/2024

LENMELDY

Orchard Therapeutics Inc

Children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD)

3/18/2024

AMTAGVI

Iovance Biotherapeutics, Inc

Adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor**

2/15/2024

CASGEVY

Vertex Pharm Inc

Patients aged 12 years and older with:

sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs)
transfusion-dependent β-thalassemia (TDT)

12/8/2023

LYFGENIA

bluebird bio Inc

Patients 12 years of age or older with sickle cell disease and a history of vaso-occlusive events

12/8/2023

ROCTAVIAN

BioMarin Pharm. Inc

Adults with severe hemophilia A (congenital factor VIII deficiency with factor VIII activity <1 IU/dL) without pre-existing antibodies to adeno-associated virus serotype 5 detected by an FDA-approved test

6/30/2023

LANTIDRA

CellTrans Inc

Adults with Type 1 diabetes who are unable to approach target HbA1c because of current repeated episodes of severe hypoglycemia despite intensive diabetes management and education

6/28/2023

VYJUVEK

Krystal Biotech Inc

Treatment of wounds in patients 6 months of age and older with dystrophic epidermolysis bullosa with mutation(s) in the collagen type VII alpha 1 chain (COL7A1) gene

5/19/2023

OMISIRGE

Gamida Cell Ltd

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

4/17/2023

ADSTILADRIN

Ferring Pharm. A/S

Adult patients with high-risk Bacillus Calmette Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors

12/16/2022

HEMGENIX

CSL Behring LLC (Uniqure)

Hemophilia B (congenital Factor IX deficiency) adults with Hemophilia B (congenital Factor IX deficiency) who:

Currently use factor IX prophylaxis therapy, or
Have current or historical life-threatening hemorrhage, or
Have repeated, serious spontaneous bleeding episodes

11/22/2022

SKYSONA

bluebird bio Inc

Boys 4-17 years of age with early, active cerebral adrenoleukodystrophy (CALD)**

9/16/2022

ZYNTEGLO

bluebird bio Inc

Adult and pediatric patients with β-thalassemia who require regular red blood cell (RBC) transfusions

8/17/2022

CARVYKTI

Janssen Biotech Inc

Adult patients with relapsed or refractory multiple myeloma who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide

2/28/2022

RETHYMIC

Enzyvant Therapeutics GmbH

Immune reconstitution in pediatric patients with congenital athymia

10/8/2021

STRATAGRAFT

Stratatech Corp/Mallinckrodt Pharm

Adults with thermal burns containing intact dermal elements for which surgical intervention is clinically indicated (deep partial-thickness burns

6/15/2021

ABECMA

Bristol-Myers Squibb (Juno)

Adult patients with relapsed or refractory multiple myeloma after two or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody

3/26/2021

BREYANZI

Bristol-Myers Squibb (Celgene)

Adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B who have:
- refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or
- refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or
- relapsed or refractory disease after two or more lines of systemic therapy
Adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (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**
Adult patients with relapsed or refractory follicular lymphoma (FL) who have received two or more prior lines of systemic therapy**
Adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least two prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor.

2/5/2021

TECARTUS

Gilead (Kite Pharma Inc)

Adult patients with relapsed or refractory mantle cell lymphoma (MCL)**
Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)

7/24/2020

ZOLGENSMA

Novartis Gene Therapies Inc

Pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene

5/24/2019

LUXTURNA

Spark Therapeutics Inc

Biallelic RPE65 mutation-associated retinal dystrophy

12/19/2017

YESCARTA

Gilead (Kite Pharma Inc)

Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy
Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma
Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy**

10/18/2017

KYMRIAH

Novartis Gene Therapies Inc

Pediatric and Young Adult (up to 25 years) Relapsed or Refractory (r/r) B-cell Acute Lymphoblastic Leukemia (ALL) that is refractory or in second or later relapse
Adult Relapsed or Refractory (r/r) Diffuse Large B-cell Lymphoma (DLBCL) after two or more lines of systemic therapy
Adult Relapsed or Refractory (r/r) Follicular Lymphoma (FL) after two or more lines of systemic therapy**

8/30/2017

MACI

Vericel Corp.

Symptomatic, single or multiple full-thickness cartilage defects of the knee with or without bone involvement in adults Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy**

12/13/2016

IMLYGIC

Amgen Inc (Biovex)

Unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery

10/27/2015

PROVENGE

Dendreon Corp

Metastatic castrate-resistant prostate cancer

4/29/2010

**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.

CGT BLAs currently under US FDA review

The following information on BLAs currently under US FDA review was obtained from company press releases.

Product

BLA Applicant

Indication

Action Due Date

clemidsogene lanparvovec (RGX-121)

Regenexbio

Mucopolysaccharidosis II (MPS II)

February 8, 2026 (3-month extension due to major amendment)

Kresladi (marnetegragene autotemcel)

Rocket Pharmaceuticals

severe Leukocyte Adhesion Deficiency-I (LAD-I)

March 28, 2026

Orca-T

Orca Bio

hematological malignancies including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and myelodysplastic syndromes (MDS)

April 6, 2026

vusolimogene oderparepvec

Replimune Group, Inc

advanced melanoma, in combination with nivolumab

April 10, 2026 (BLA resubmission)

DTX401

Ultragenyx

Glycogen Storage Disease Type Ia (GSDIa)

Under filing review, estimated priority review action date July 30, 2026

Upcoming FDA AdComm meetings

No upcoming meetings of the Cellular, Tissue, and Gene Therapies Advisory committee for CGT topics have been announced.

Past and Upcoming FDA Town Halls

Individualized Therapies On The Rise- November 20, 2025

OTP Town Hall: Gene Therapy Manufacturing CMC and Facility Readiness for BLAs and Post-licensure Changes- October 22, 2025

CBER Guidance Agenda 2026

For CGT

Safety Testing of Human Allogeneic Cells Expanded for Use in Cell-Based Medical Products; Guidance for Industry
Potency Assurance for Cellular and Gene Therapy Products; Guidance for Industry
Potency Assessment of Active Immunotherapy Products; Draft Guidance for Industry
Post Approval Methods to Capture Safety and Efficacy Data for Cell and Gene Therapy Products; Guidance for Industry
Chimeric Antigen Receptor (CAR) T Cell Products: Development Considerations for NonOncology Indications; Draft Guidance for Industry
Considerations for Clinical Study of Porcine Derived Solid Organs for Xenotransplantation; Draft Guidance for Industry • Considerations for Testing, Sampling, and Archiving of Xenotransplantation Products; Draft Guidance for Industry
Expedited Programs for Regenerative Medicine Therapies for Serious Conditions; Guidance for Industry
Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products; Guidance for Industry
Leveraging Prior Knowledge in the Development of Human Gene Therapy Products Incorporating Genome Editing; Draft Guidance for Industry
Recommendations to Reduce the Risk of Transmission of Mycobacterium tuberculosis by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps); Guidance for Industry
Recommendations to Reduce the Risk of Transmission of Disease Agents Associated with Sepsis for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps); Guidance for Industry
Recommendations to Reduce the Risk of Transmission of Human Immunodeficiency Virus (HIV) by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps); Guidance for Industry
Recommendations to Reduce the Risk of Transmission of Hepatitis C Virus (HCV) by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps); Guidance for Industry
Recommendations to Reduce the Risk of Transmission of Hepatitis B Virus (HBV) by Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps); Guidance for Industry
Recommendations for Determining Eligibility of Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps); Guidance for Industry
Establishing a Plausible Mechanism Supporting Approval of Individualized Therapies to Treat Rare Genetic Disorders; Draft Guidance for Industry

Also applicable to CGT

Standardized Format for Electronic Submission for Marketing Applications Content for the Planning of Bioresearch Monitoring (BIMO) Inspections for Center for Biologics Evaluation and Research Submissions; Guidance for Industry
Recommendations for Validation and Implementation of Alternative Microbial Methods for Testing of Biologics, Draft Guidance for Industry

Journal publications and webposts from FDA:

Flexible Requirements for Cell and Gene Therapies to Advance Innovation

FDA’s New Plausible Mechanism Pathway

Advancing CAR T-Cell Therapy: Evidence-Based Trial Design for Chimeric Antigen Receptor T-Cell Therapy in Oncology

‍FDA Public Meeting: Onshoring Manufacturing of Drugs and Biological Products – September 30, 2025
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Lessons Learned From the Chemistry, Manufacturing, and Controls (CMC) Development and Readiness Pilot (CDRP) Program - September 10, 2025
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‍On the RISE: Controls in Rare Disease Clinical Trials for Small and Diminishing Populations – September 3, 2025
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FDA Roundtable on Cell and Gene Therapy June 5, 2025
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OTP Town Hall: Best Practices for Regulatory Interactions with OTP – December 12, 2024

‍Meeting 2: Patient and Care Partner Perspectives on Early Enrollment into Gene Therapy Clinical Trials for Rare Diseases –
December 4, 2024

‍Workshop on Integration Site Analysis During Long Term Follow-Up for Gene Therapies with Integrating Viral Vectors –
November 19, 2024

‍Finding Your Support Team While Participating in a Clinical Trial –
October 30, 2024
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‍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
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‍Nonclinical Assessment of Cell and Gene Therapy Products
August 30, 2023
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‍Decentralized Clinical Trials
June 20, 2023
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‍Regulatory Education for Industry (REdI) Annual Conference 2023
June 5-9, 2023
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‍OTP Town Hall: Cell Therapy Chemistry, Manufacturing, and Controls – June 2023
June 8, 2023
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‍OTP Town Hall: Gene Therapy Chemistry, Manufacturing, and Controls – April 2023
April 25, 2023‍
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‍Methods and Approaches for Capturing Post-Approval Safety and Efficacy Data on Cell and Gene Therapy Products
April 27, 2023
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‍Clinical Trials: The Patient Experience
April 13, 2023
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‍FDA CBER Office of Therapeutic Products (OTP) Advanced Manufacturing and Analytical Technologies (AMAT) for Regenerative Medicine Therapies (RMT) Workshop
March 14, 2023
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‍‍OTAT Town Hall: Clinical Development of Gene Therapy Products for Rare Diseases
February 7, 2023
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‍Assessing Genetic Heterogeneity in the Context of Genome Editing Off-Targets in Gene Therapy Products
December 16, 2022
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‍OTAT Town Hall: Cell Therapy Chemistry, Manufacturing, and Controls
December 7, 2022
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‍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
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‍FDA CBER OTAT Patient-Focused Drug Development Listening Meeting — Patient Perspectives on Gene Therapy Products
November 15, 2022
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‍Natural History Studies to Support Regenerative Medicine: A How-To Webinar
October 27, 2022
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‍OTAT Town Hall: Gene Therapy Chemistry, Manufacturing, and Controls
September 29, 2022
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‍2022 Center for Biologics Evaluation and Research (CBER) Science Symposium
September 20-22, 2022
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‍Regulatory Education for Industry (REdI) Annual Conference 2022
June 6 - 10, 2022
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‍Annual Patient Engagement & Regenerative Medicine Meeting 2022: An FDA CBER Workshop for Patient Advocates
May 24, 2022
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‍RegenMedEd Webinar: The Critical Role of Patients in Advancing Gene Therapy Treatments for Rare Diseases
March 9, 2022

Regulatory Roundup LIVE

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.

Stay current with the latest updates in US FDA news from our team of Regulatory experts.

DHC FDA-guidance related articles

BLA review updates

US FDA CGT Approvals to date

CGT BLAs currently under US FDA review

Upcoming FDA AdComm meetings

Past and Upcoming FDA Town Halls

FDA Guidance Docs

Other FDA Guidance Docs of Interest to CGT

Draft FDA Guidance: open for public comment

ICH Guidelines

Regulatory Roundup LIVE