After nearly a decade of clinical trials, a new gene therapy called ZEVASKYN™ has been approved by the Food and Drug Administration (FDA) to treat epidermolysis bullosa (EB) in pediatric patients. EB is a rare genetic skin disease that causes painful blistering and can have internal involvement as well.
Marissa J. Perman, MD, Director of the Epidermolysis Bullosa Multidisciplinary Clinic at Children’s Hospital of Philadelphia (CHOP), says that CHOP plans to be one of five U.S. sites to offer this groundbreaking treatment, developed by Abeona Therapeutics. Dr. Perman provided guidance to Abeona Therapeutics in preparation for ZEVASKYN™ going to market, especially with respect to making the therapy as patient-friendly as possible. She expects that CHOP will administer ZEVASKYN™ to three to five EB patients within the first year.
“We currently have patients in our clinic not just from the Philadelphia area, but from New York to Florida,” says Dr. Perman. “We also see patients come to us from as far away as the Middle East and South America.”
Currently no “cure” exists to address the underlying cause of EB. Instead, conventional treatments and gene therapies are used locally to help heal individual wounds.
The type and the severity of EB are determined by the specific gene variant that causes the disease. Different types of EB can affect different layers of skin tissue, but in general EB affects skin’s structure and strength, and the connectivity of the skin’s layers.
The common symptom of all people with EB is that they have extremely fragile skin. Blisters can form in response to minor trauma, even to rubbing the skin, and can advance to become open, bleeding sores, prone to infection and in some cases scarring. Some children also develop blisters and sores inside the body, such as in the mouth or the lining of the esophagus (food pipe). It can also affect other internal organs.
How ZEVASKYN™ works
ZEVASKYN™ is an ex vivo gene therapy, meaning a process in which a child's cells are removed and modified outside of their body. ZEVASKYN™ treats the recessive dystrophic form of epidermolysis bullosa (RDEB). For this therapy, doctors introduce a corrected copy of the gene to a biopsy of the patient’s skin cells. Those engineered cells are then used to grow up to 12 credit card-sized “sheets” of skin that can be grafted over the child’s open wound. The corrected genes in the skin graft will promote wound healing.
Patients are monitored closely in the hospital for one to two weeks after the procedure to ensure the graft is accepted. This therapy is intended for larger wound areas on relatively flat surfaces of the body.
Dr. Perman says that in clinical trials, patients were followed for five to six years after their skin grafts were placed, and this produced “promising data on the durability of the skin grafts, meaning that the wound areas that received grafts had stayed closed.”
ZEVASKYN™ builds on another approved gene therapy
This is not the first gene therapy approved for EB treatment. In May 2023 the FDA approved Vyjuvek® as a topical wound treatment for patients 6 months and older with dystrophic epidermolysis bullosa (DEB). Because Vyjuvek® delivers the corrected gene in a topically applied gel, it is typically used to help heal smaller wounds. CHOP also offers Vyjuvek® to DEB patients.
Another topical wound treatment that is not based on gene therapy, Filsuvez®, was FDA approved for children 6 months and older in December 2023.
CHOP’s leadership in gene therapy and collaborative specialty care
Patients receiving ZEVASKYN™ will be treated by CHOP’s EB Multidisciplinary Clinic. What makes CHOP ideally situated to launch this new treatment? Dr. Perman cites the hospital’s longstanding global leadership in cell and gene therapies.
CHOP’s Cell Therapy and Transplant program is one of the most experienced gene therapy programs in the world, and it is the only program in the United States to be a Qualified Treatment Center for all six FDA-approved stem cell-based gene therapies for genetic blood and metabolic disorders (Zynteglo, Skysona, Lyfgenia, Casgevy thalassemia, Casgevy SCD and Lenmeldy). CHOP was directly involved in the FDA approval process for many of them.
The Cell Based Therapy Laboratory, which has been processing cells for transplants for decades, has taken on an increasing number of experimental cellular therapy protocols since 2010. CHOP is also home to the Raymond G. Perelman Center for Cellular and Molecular Therapeutics Clinical Vector Core, which utilizes a vast array of state-of-the-art technology for preclinical and clinical vector production and characterization used in the development of gene therapies.
The EB Multidisciplinary Clinic, open since 2017, already works with more than 30 different subspecialties to address the complexities of this systemic inflammatory disease, including dermatology, sedation, surgery, gastroenterology, nursing, physical therapy, occupational therapy, psychology and more.
“One reason this is so complicated is that it involves so many departments and divisions – not just on the research and clinical side, but the administrative, financial and research sides as well,” Dr. Perman says. “Our clinic is already very experienced at that kind of collaborative multidisciplinary care and follow-up.”
The future of EB gene therapy
Dr. Perman hopes that the approval of ZEVASKYN™ is the “next step to a more robust therapy that will, one day, lead to a cure for EB.” CHOP continues to participate in phase I and II clinical trials for other topical wound care therapies. In the short term, CHOP’s EB Multidisciplinary Clinic will focus on rolling out these gene therapies. While it’s not advised to treat a single wound with multiple therapies, a patient with EB may receive different gene therapies and wound-care therapies simultaneously on different parts of the body.
Healing chronic, often painful wounds will go a long way to improving the quality of life for children faced with lifelong management of this disease.
"We want to be the place where families go to get the specialized care they cannot get anywhere else,” Dr. Perman says.
Disclosure: Marissa J. Perman, MD, has been a consultant to Abeona Therapeutics and will be a principal investigator doing research associated with ZEVASKYN™ moving forward.
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After nearly a decade of clinical trials, a new gene therapy called ZEVASKYN™ has been approved by the Food and Drug Administration (FDA) to treat epidermolysis bullosa (EB) in pediatric patients. EB is a rare genetic skin disease that causes painful blistering and can have internal involvement as well.
Marissa J. Perman, MD, Director of the Epidermolysis Bullosa Multidisciplinary Clinic at Children’s Hospital of Philadelphia (CHOP), says that CHOP plans to be one of five U.S. sites to offer this groundbreaking treatment, developed by Abeona Therapeutics. Dr. Perman provided guidance to Abeona Therapeutics in preparation for ZEVASKYN™ going to market, especially with respect to making the therapy as patient-friendly as possible. She expects that CHOP will administer ZEVASKYN™ to three to five EB patients within the first year.
“We currently have patients in our clinic not just from the Philadelphia area, but from New York to Florida,” says Dr. Perman. “We also see patients come to us from as far away as the Middle East and South America.”
Currently no “cure” exists to address the underlying cause of EB. Instead, conventional treatments and gene therapies are used locally to help heal individual wounds.
The type and the severity of EB are determined by the specific gene variant that causes the disease. Different types of EB can affect different layers of skin tissue, but in general EB affects skin’s structure and strength, and the connectivity of the skin’s layers.
The common symptom of all people with EB is that they have extremely fragile skin. Blisters can form in response to minor trauma, even to rubbing the skin, and can advance to become open, bleeding sores, prone to infection and in some cases scarring. Some children also develop blisters and sores inside the body, such as in the mouth or the lining of the esophagus (food pipe). It can also affect other internal organs.
How ZEVASKYN™ works
ZEVASKYN™ is an ex vivo gene therapy, meaning a process in which a child's cells are removed and modified outside of their body. ZEVASKYN™ treats the recessive dystrophic form of epidermolysis bullosa (RDEB). For this therapy, doctors introduce a corrected copy of the gene to a biopsy of the patient’s skin cells. Those engineered cells are then used to grow up to 12 credit card-sized “sheets” of skin that can be grafted over the child’s open wound. The corrected genes in the skin graft will promote wound healing.
Patients are monitored closely in the hospital for one to two weeks after the procedure to ensure the graft is accepted. This therapy is intended for larger wound areas on relatively flat surfaces of the body.
Dr. Perman says that in clinical trials, patients were followed for five to six years after their skin grafts were placed, and this produced “promising data on the durability of the skin grafts, meaning that the wound areas that received grafts had stayed closed.”
ZEVASKYN™ builds on another approved gene therapy
This is not the first gene therapy approved for EB treatment. In May 2023 the FDA approved Vyjuvek® as a topical wound treatment for patients 6 months and older with dystrophic epidermolysis bullosa (DEB). Because Vyjuvek® delivers the corrected gene in a topically applied gel, it is typically used to help heal smaller wounds. CHOP also offers Vyjuvek® to DEB patients.
Another topical wound treatment that is not based on gene therapy, Filsuvez®, was FDA approved for children 6 months and older in December 2023.
CHOP’s leadership in gene therapy and collaborative specialty care
Patients receiving ZEVASKYN™ will be treated by CHOP’s EB Multidisciplinary Clinic. What makes CHOP ideally situated to launch this new treatment? Dr. Perman cites the hospital’s longstanding global leadership in cell and gene therapies.
CHOP’s Cell Therapy and Transplant program is one of the most experienced gene therapy programs in the world, and it is the only program in the United States to be a Qualified Treatment Center for all six FDA-approved stem cell-based gene therapies for genetic blood and metabolic disorders (Zynteglo, Skysona, Lyfgenia, Casgevy thalassemia, Casgevy SCD and Lenmeldy). CHOP was directly involved in the FDA approval process for many of them.
The Cell Based Therapy Laboratory, which has been processing cells for transplants for decades, has taken on an increasing number of experimental cellular therapy protocols since 2010. CHOP is also home to the Raymond G. Perelman Center for Cellular and Molecular Therapeutics Clinical Vector Core, which utilizes a vast array of state-of-the-art technology for preclinical and clinical vector production and characterization used in the development of gene therapies.
The EB Multidisciplinary Clinic, open since 2017, already works with more than 30 different subspecialties to address the complexities of this systemic inflammatory disease, including dermatology, sedation, surgery, gastroenterology, nursing, physical therapy, occupational therapy, psychology and more.
“One reason this is so complicated is that it involves so many departments and divisions – not just on the research and clinical side, but the administrative, financial and research sides as well,” Dr. Perman says. “Our clinic is already very experienced at that kind of collaborative multidisciplinary care and follow-up.”
The future of EB gene therapy
Dr. Perman hopes that the approval of ZEVASKYN™ is the “next step to a more robust therapy that will, one day, lead to a cure for EB.” CHOP continues to participate in phase I and II clinical trials for other topical wound care therapies. In the short term, CHOP’s EB Multidisciplinary Clinic will focus on rolling out these gene therapies. While it’s not advised to treat a single wound with multiple therapies, a patient with EB may receive different gene therapies and wound-care therapies simultaneously on different parts of the body.
Healing chronic, often painful wounds will go a long way to improving the quality of life for children faced with lifelong management of this disease.
"We want to be the place where families go to get the specialized care they cannot get anywhere else,” Dr. Perman says.
Disclosure: Marissa J. Perman, MD, has been a consultant to Abeona Therapeutics and will be a principal investigator doing research associated with ZEVASKYN™ moving forward.
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