11 gene therapies expected to receive FDA approval or submit regulatory filings in 2022

Since August 2017 (Kymriah) tisagenlecleucel was first approved in the US for the treatment of acute lymphoblastic leukemia, at least 8 gene therapies have been approved by the US FDA, including the recently approved Carvykti (ciltacabtagene autoleucel), see below for details table
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(Drawing by WuXi AppTec content team, click to see the larger image, in parentheses the company has acquired the R&D company of the product)

In the past February, Carvykti, jointly developed by Janssen and Legend Bio, has been approved by the FDA, three gene therapies may be approved by the FDA this year, and another eight are expected to submit Biologics License Applications (BLA) by the end of the year.
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(Drawing by WuXi AppTec content team, click to enlarge)

1.
Name of therapy: Betibeglogene autotemcel

Company Name: Bluebird Bio

Indications: beta thalassemia

Bluebird Bio has two gene therapies expected to receive FDA approval in 2022
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Betibeglogene autotemcel (beti-cel) is an in vitro gene therapy of hematopoietic stem cells for the treatment of patients with beta thalassemia who require routine red blood cell transfusions

2.
Name of therapy: Elivaldogene autotemcel

Company: Bluebird Bio

Indications: Cerebral adrenoleukodystrophy

The second gene therapy for Bluebird Bio under review by the FDA is elivaldogene autotemcel (eli-cel) for the treatment of early-stage cerebral adrenoleukodystrophy (CALD) patients under the age of 18 who carry a mutation in the ABCD1 gene
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The disease is caused by mutations in the ABCD1 gene, which affect the production of the ALD protein, which subsequently leads to the toxic accumulation of very long-chain fatty acids (VLCFAs), mainly in the adrenal glands, the white matter of the brain and spinal cord

3.
Name of therapy: Nadofaragene firadenovec

Company Name: FerGene (Ferring)

Indication: Bladder cancer

Gene therapies under FDA review in 2022 also include nadofaragene firadenovec (Instiladrin), developed by Ferring Pharmaceuticals subsidiary FerGene for the treatment of high-grade non-muscle-invasive bladder cancer (high-grade NMIBC) that has not responded well to Bacille Calmette-Guérin (BCG).
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Nadofaragene firadenovec was originally developed by the Finnish gene therapy company FKD Therapies.

4.
Therapeutic name: Beremagene geperpavec

Company: Krystal Biotech

Indications: dystrophic epidermolysis bullosa

The first to introduce a gene therapy candidate with an impending BLA submission in the U.
S.
is Krystal Biotech's bermagene geperpavec, a topical gene therapy expressing collagen type VII (COL7) for dystrophic epidermis bullosa Debilitating Syndrome (DEB), a rare and serious disease that affects skin and mucosal tissues
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The therapy is designed to treat DEB at the molecular level by providing the patient's skin cells with a template to manufacture the normal COL7 protein

5.
Name of therapy: Etranacogene dezaparvovec

Companies: uniQure, CSL Behring

Indications: Hemophilia B

Etranacogene dezaparvovec, developed by uniQure in collaboration with CSL Behring, is designed to deliver a gene expressing a FIX Padua variant using an adeno-associated virus 5 (AAV5) vector for the treatment of moderate-to-severe hemophilia
B.
It has demonstrated safety and met primary and secondary efficacy endpoints in its Phase 3 trial

6.
Name of therapy: Valoctocogene roxaparvovec

Company Name: BioMarin Pharmaceutical

Indications: Hemophilia A

BioMarin's gene therapy candidate, valoctocogene roxaparvovec, is also an AAV5-based gene therapy and is poised for a BLA submission this year
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The therapy uses an AAV5 viral vector to deliver a transgene expressing coagulation factor VIII for the treatment of hemophilia A, an inherited and rare bleeding disorder

7.
Name of therapy: Eladocagene exuparvovec

Company: PTC Therapeutics

Indications: Aromatic L-amino acid decarboxylase deficiency

PTC Therapeutics' eladocagene exuparvovec (PTC-AADC) is a gene replacement therapy that delivers a single dose of the human dopa decarboxylase (DDC) gene into the putamen of the brain for the treatment of aromatic L-amino acid decarboxylase deficiency ( AADCD), a rare genetic disorder that affects the brain
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Analysis of 5-year results from three Phase 1 and 2 clinical trials showed sustained improvements in motor function and cognitive performance in children with AADCD

8.
Therapeutic name: Afamitresgene autoleucel

Company: Adaptimmune Therapeutics

Indications: Membranous sarcoma or myxoid/round cell liposarcoma (MRCLS)

Afamitresgene autoleucel (afami-cel) is an engineered T-cell therapy targeting the MAGE-A4 antigen developed by Adaptimmune Therapeutics
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The therapy met its primary efficacy endpoint in its ongoing Phase 2 study in synovial sarcoma and myxoid/round cell liposarcoma (MRCLS)

9.
Therapy name: CTX001

Company names: CRISPR Therapeutics, Vertex Pharmaceuticals

Indications: beta thalassemia; sickle cell anemia

CTX001 is a non-viral vector gene editing therapy developed by CRISPR Therapeutics and Vertex for the treatment of patients with transfusion-dependent beta thalassemia (TDT) or severe sickle cell disease (SCD) by in vitro The patient's hematopoietic stem cells are engineered to produce high levels of fetal hemoglobin (HbF) in red blood cells
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The therapy has completed patient enrollment in its ongoing Phase 3 study and has dosed more than 70 patients
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CTX001 has been granted Regenerative Medicine Advanced Therapy (RMAT) designation, Fast Track and Orphan Drug designation by the US FDA for the treatment of TDT and SCD
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Vertex plans to submit a global (including U.
S.
FDA) regulatory filing for CTX001 in both indications by the end of 2022
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10.
Treatment Name: EB-101

Company: Abeona Therapeutics

Indications: Recessive dystrophic epidermolysis bullosa

Another COL7A1 gene-targeted therapy expected to file in the US this year is Abeona's EB-101
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The therapy is an in vitro gene-corrected autologous cell therapy that inserts the COL7A1 collagen gene into the patient's own skin cells (keratinocytes)
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The therapy is being studied in a Phase 3 safety and efficacy clinical trial for the treatment of recessive dystrophic epidermolysis bullosa (RDEB), a rare connective tissue disorder that has not an approved therapy
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In Phase 1/2 studies, EB-101 has shown substantial wound healing and long-term pain relief for up to six years
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Abeona has completed patient enrollment in its Phase 3 trial and expects to provide first-line results in the third quarter of 2022, followed by a BLA filing in late 2022 or early 2023
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11.
Therapy name: OTL-103

Company Name: Orchard Therapeutics

Indication: Wiskott-Aldrich syndrome

Orchard Therapeutics' OTL-103 is an autologous hematopoietic stem cell gene therapy consisting of CD34+ cells transfected in vitro with a lentiviral vector encoding the Wiskott-Aldrich syndrome (WAS) gene, designed to treat Wiskott-Aldrich syndrome by a single injection , a rare inherited immune deficiency disorder
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The therapy has been granted Orphan Drug Designation and Rare Pediatric Disease (RPD) designation by the FDA
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Phase 3 clinical trials evaluating efficacy and safety are currently underway, and Orchard plans to discuss its potential BLA application with the FDA in early 2022
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