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LONDON – .
“I think there is a palpable sense that we are close to some breakthroughs for EB,” which may include “a cure for this intractable disease,” said Jouni Uitto, MD, PhD, in welcoming delegates to the meeting, held in January 2020.
Dr. Uitto, professor of dermatology and cutaneous biology, and biochemistry and molecular biology, at Sidney Kimmel Medical College, Philadelphia, said that the “breadth of academia-based basic science has been tremendous over the past 3 decades. We can now identify 21 different genes harboring mutations associated with different EB phenotypes, and we have a pretty good understanding how those mutations actually explain the phenotypic spectrum of different forms of EB.”
Importantly, “there are now perhaps as many as a dozen different clinical trials that are in the early stages of trying to find a permanent cure for this disease,” Dr. Uitto said, with some that are looking at fixing the underlying defect once and for all, or at the very least, counteracting subsequent complications. “The spectrum varies from attempting to enhance wound healing to gene repair, gene replacement, protein replacement therapies, cell-based therapies. There is a whole spectrum of often complementary approaches that we believe will lead to a cure and treatment for this disease. We look forward to developing therapies which will be helpful to the benefit of all the patients with EB,” said Dr. Uitto, who is also chair of the department of dermatology and cutaneous biology at Sidney Kimmel Medical College.
EB research is gathering ‘momentum’
John McGrath, MD, professor of molecular dermatology, King’s College, London, chaired a session on the latest in cell manipulation research and made the following comment: “A few years ago, we were making progress, but we were chatting about a lot of the same things; but now, suddenly there seems to be momentum, re-energy, rediscovery, real progress.”
Dr. McGrath noted that gene and cell research, and preclinical development, were culminating in clinical trials and potentially products that could change the way clinicians thought about managing patients with EB. “That prospect of getting closer and closer to real treatments, and maybe even a cure” is becoming more of a reality, he said.
Dr. McGrath is also head of the genetic skin disease group at King’s College London, and an honorary consultant dermatologist at St. John’s Institute of Dermatology, part of the Guy’s and St. Thomas’ NHS Foundation Trust in London. He has been a principal investigator for clinical trials of fibroblast cell therapy and allogeneic intravenous mesenchymal stromal cells (MSCs) therapy.
“It has been a joy for me to see the benefits of those clinical trials. There is nothing like it as an investigator when you see an intervention make a difference to a patient,” Dr. McGrath said. “For me, it was just a real eye opener when I saw the skin changes in a child that received intravenous allogeneic MSCs. The skin changed dramatically, it went from red and inflamed to calm and pink, [giving a] first glimpse into something that might be reversible, treatable, not just papering over the cracks.”
Correcting the genetic defect
The most severe form of RDEB is caused by mutations in COL7A1, the gene for collagen type 7 (COL7), the major connective component of the skin, anchoring the epidermis to the dermis. Its absence results in skin that can be so fragile it has been likened to the wings of a butterfly and results in severe blistering after very little trauma.
There is a lot of research on how to correct the underlying genetic defect, either by replacing COL7A1 entirely, repairing the gene, or editing the gene so that COL 7 can be produced in situ and prevent the formation of wounds and heal those that might already be present.
“The excitement is obvious,” said Jakub Tolar, MD, PhD, professor in the department of pediatrics, blood and marrow transplantation, and dean of the University of Minnesota Medical School, Minneapolis, who chaired a session on gene and gene manipulation therapies. “If one can go and correct that information, it follows that everything else is going to be okay,” he said. “Only it’s not. I think that it’s pretty clear that more than gene correction is needed.”
Some of the approaches to replace the faulty gene discussed at the meeting involved taking skin biopsy samples from a healthy area of skin from a patient with RDEB, isolating specific skin cells (fibroblasts, keratinocytes, or both), transferring a healthy copy of the COL7A1 gene into those cells – then expanding the population to form sheets of cells that can be grafted onto the wounds of the same patient.
Clinical trials of gene therapy for RDEB
Clinical trials with these novel gene-corrected, tissue-engineered grafts have already started, including EBGraft, a phase 1/2 open, nonrandomized, proof-of-concept trial using genetically corrected sheets of fibroblasts and keratinocytes, conducted by Alain Hovnanian, MD, PhD, Necker-Enfants Malades Hospital in Paris, and associates.
Then there is the phase 3 VIITAL trial being conducted at Stanford (Calif.) University by Jean Tang, MD, PhD, and colleagues. Recruitment in this open trial, which will enroll 10-15 patients with RDEB, has just started. The aim of the study is to investigate the efficacy and safety of EB-101, an autologous cell therapy that corrects COL7A1 in keratinocytes.
Positive findings from a phase 1/2 study with EB-101 were presented in a poster at the meeting by Emily Gorell, DO, a postdoctoral medical fellow in dermatology, at Stanford University and her associates. The trial included seven patients with RDEB who were treated and followed for 3 to 6 years. Data from that study showed that there were no serious adverse events and 95% of patients’ wounds that were treated (36/38) were healed by at least 50%, based on an Investigator Global Assessment at 6 months. In comparison, none of the untreated wounds had healed by that time point. “There was evidence of C7 [collagen 7] restoration at 2 years in two participants,” and wound healing was associated with both reduced pain and itch, the investigators wrote in the poster.
Another approach to this so-called ‘ex-vivo’ gene therapy is to take the patient’s cells via a small skin biopsy, genetically modify them, expand the population of these modified cells, and then inject them back into the patient. This approach was described by Peter Marinkovich, MD, of the department of dermatology at Stanford University, during an oral presentation and in a poster at the meeting.
Dr. Marinkovich discussed the results of an ongoing phase 1/2 study in which six subjects with RDEB – five adults and one child – were treated intradermally with genetically modified fibroblasts in a preparation currently known as FCX-007.
“Before we had to graft the cells, take the patients into the OR [operating room], with the risks of general anesthesia, but here we don’t have to take the patients to the OR, we just take them into the hospital for a day, inject their wounds and then send them on their way,” Dr. Marinkovich said. Interim findings show that the patients have tolerated the therapy very well up to 52 weeks, he noted.
A greater percentage of wounds were healed by more than 50% following treatment with FCX-007 than those left untreated at weeks 4 (80% versus 20%), 12 (90% versus 44%), 25 (75% versus 50%), and 52 (83% versus 33%).
These results have been used to inform the design of the upcoming phase 3 study, DEFI-RDEB. The multicenter intrapatient randomized, controlled, open-label study is evaluating FCX-007 in the treatment of persistent nonhealing wounds in about 20 people with RDEB.
The promise of ‘off-the-shelf’ topical gene therapy
Another study Dr. Marinkovich is involved with is a phase 1/2 study of beremagene geperpavec (B-VEC), an “in-vivo” gene therapy. B-VEC is a topically administered therapy containing a replication-deficient, nonintegrating viral vector that contains two functional COL7A1 genes. The concept is that, when applied directly onto the skin, the virus gets into the skin and carries with it the healthy gene copies; these get taken up by the skin cells, which then produce COL7.
Initially, two patients with generalized severe RDEB were studied. B-VEC was applied to one of two wounds and a placebo to the other wound in each patient. Another four patients were then enrolled and studied for 3 months. Nine of 10 wounds closed completely after initial administration of B-VEC, with an average time to 100% wound closure of 17.4 days. The average duration of wound closure has been 113 days so far.
“One chronic wound that was originally open for over 4 years closed completely following B-VEC readministration. The wound has remained closed for 100 days,” Dr. Marinkovich and associates reported in a poster at the meeting. A postimaging study showed that COL7 was being produced from 48 hours to up to 90 days later.
“I’m really excited about this type of therapy,” Dr. Marinkovich said during an oral presentation. Unlike the ex-vivo gene therapy approach, where each patient’s cells have to be taken by a biopsy, altered, engineered, and expanded, which takes specialized facilities that can vary by country and location, this in-vivo gene therapy can be considered an “off-the shelf” treatment that can be shipped all over the world and could reach many patients. “It’s another weapon in our armamentarium against this deadly disease that we are all fighting against together,” Dr. Marinkovich added.
EBGRAFT is supported by Cure EB. The VIITAL trial is sponsored by Abeona Therapeutics. The phase 1/2 trials of EB-101 were funded by grants from the National Institutes of Health, EB Research Partnership, EM Medical Research Foundation, and Abeona Therapeutics. The FCX-007 phase 1/2 study was supported by Fibrocell Technologies. The upcoming phase 3 will be funded by Fibrocell Technologies in collaboration with Castle Creek Pharmaceuticals. The B-VEC study is supported by Krystal Biotech.
Dr. Uitto and Dr. McGrath had no potential conflicts of interest to report. Dr. Tolar has received funding from the National Institutes of Health, various EB charities and the Richard M. Schulze Family Foundation (RMSFF). He disclosed receiving honoraria or consultation fees from Ticeba/RHEACELL GmbH and Taiga Biosciences. Dr. Marinkovich disclosed being an investigator working on RDEB-related research projects in collaboration with Krystal Biotech, Fibrocell Technologies, Abeona Therapeutics, and Wings (formerly ProQR).
SOURCES: Gorell E et al. EB 2020, Poster 124; Marinkovich MP et al. EB 2020, Poster 123; Marinkovich MP et al. EB 2020, Poster 52.
LONDON – .
“I think there is a palpable sense that we are close to some breakthroughs for EB,” which may include “a cure for this intractable disease,” said Jouni Uitto, MD, PhD, in welcoming delegates to the meeting, held in January 2020.
Dr. Uitto, professor of dermatology and cutaneous biology, and biochemistry and molecular biology, at Sidney Kimmel Medical College, Philadelphia, said that the “breadth of academia-based basic science has been tremendous over the past 3 decades. We can now identify 21 different genes harboring mutations associated with different EB phenotypes, and we have a pretty good understanding how those mutations actually explain the phenotypic spectrum of different forms of EB.”
Importantly, “there are now perhaps as many as a dozen different clinical trials that are in the early stages of trying to find a permanent cure for this disease,” Dr. Uitto said, with some that are looking at fixing the underlying defect once and for all, or at the very least, counteracting subsequent complications. “The spectrum varies from attempting to enhance wound healing to gene repair, gene replacement, protein replacement therapies, cell-based therapies. There is a whole spectrum of often complementary approaches that we believe will lead to a cure and treatment for this disease. We look forward to developing therapies which will be helpful to the benefit of all the patients with EB,” said Dr. Uitto, who is also chair of the department of dermatology and cutaneous biology at Sidney Kimmel Medical College.
EB research is gathering ‘momentum’
John McGrath, MD, professor of molecular dermatology, King’s College, London, chaired a session on the latest in cell manipulation research and made the following comment: “A few years ago, we were making progress, but we were chatting about a lot of the same things; but now, suddenly there seems to be momentum, re-energy, rediscovery, real progress.”
Dr. McGrath noted that gene and cell research, and preclinical development, were culminating in clinical trials and potentially products that could change the way clinicians thought about managing patients with EB. “That prospect of getting closer and closer to real treatments, and maybe even a cure” is becoming more of a reality, he said.
Dr. McGrath is also head of the genetic skin disease group at King’s College London, and an honorary consultant dermatologist at St. John’s Institute of Dermatology, part of the Guy’s and St. Thomas’ NHS Foundation Trust in London. He has been a principal investigator for clinical trials of fibroblast cell therapy and allogeneic intravenous mesenchymal stromal cells (MSCs) therapy.
“It has been a joy for me to see the benefits of those clinical trials. There is nothing like it as an investigator when you see an intervention make a difference to a patient,” Dr. McGrath said. “For me, it was just a real eye opener when I saw the skin changes in a child that received intravenous allogeneic MSCs. The skin changed dramatically, it went from red and inflamed to calm and pink, [giving a] first glimpse into something that might be reversible, treatable, not just papering over the cracks.”
Correcting the genetic defect
The most severe form of RDEB is caused by mutations in COL7A1, the gene for collagen type 7 (COL7), the major connective component of the skin, anchoring the epidermis to the dermis. Its absence results in skin that can be so fragile it has been likened to the wings of a butterfly and results in severe blistering after very little trauma.
There is a lot of research on how to correct the underlying genetic defect, either by replacing COL7A1 entirely, repairing the gene, or editing the gene so that COL 7 can be produced in situ and prevent the formation of wounds and heal those that might already be present.
“The excitement is obvious,” said Jakub Tolar, MD, PhD, professor in the department of pediatrics, blood and marrow transplantation, and dean of the University of Minnesota Medical School, Minneapolis, who chaired a session on gene and gene manipulation therapies. “If one can go and correct that information, it follows that everything else is going to be okay,” he said. “Only it’s not. I think that it’s pretty clear that more than gene correction is needed.”
Some of the approaches to replace the faulty gene discussed at the meeting involved taking skin biopsy samples from a healthy area of skin from a patient with RDEB, isolating specific skin cells (fibroblasts, keratinocytes, or both), transferring a healthy copy of the COL7A1 gene into those cells – then expanding the population to form sheets of cells that can be grafted onto the wounds of the same patient.
Clinical trials of gene therapy for RDEB
Clinical trials with these novel gene-corrected, tissue-engineered grafts have already started, including EBGraft, a phase 1/2 open, nonrandomized, proof-of-concept trial using genetically corrected sheets of fibroblasts and keratinocytes, conducted by Alain Hovnanian, MD, PhD, Necker-Enfants Malades Hospital in Paris, and associates.
Then there is the phase 3 VIITAL trial being conducted at Stanford (Calif.) University by Jean Tang, MD, PhD, and colleagues. Recruitment in this open trial, which will enroll 10-15 patients with RDEB, has just started. The aim of the study is to investigate the efficacy and safety of EB-101, an autologous cell therapy that corrects COL7A1 in keratinocytes.
Positive findings from a phase 1/2 study with EB-101 were presented in a poster at the meeting by Emily Gorell, DO, a postdoctoral medical fellow in dermatology, at Stanford University and her associates. The trial included seven patients with RDEB who were treated and followed for 3 to 6 years. Data from that study showed that there were no serious adverse events and 95% of patients’ wounds that were treated (36/38) were healed by at least 50%, based on an Investigator Global Assessment at 6 months. In comparison, none of the untreated wounds had healed by that time point. “There was evidence of C7 [collagen 7] restoration at 2 years in two participants,” and wound healing was associated with both reduced pain and itch, the investigators wrote in the poster.
Another approach to this so-called ‘ex-vivo’ gene therapy is to take the patient’s cells via a small skin biopsy, genetically modify them, expand the population of these modified cells, and then inject them back into the patient. This approach was described by Peter Marinkovich, MD, of the department of dermatology at Stanford University, during an oral presentation and in a poster at the meeting.
Dr. Marinkovich discussed the results of an ongoing phase 1/2 study in which six subjects with RDEB – five adults and one child – were treated intradermally with genetically modified fibroblasts in a preparation currently known as FCX-007.
“Before we had to graft the cells, take the patients into the OR [operating room], with the risks of general anesthesia, but here we don’t have to take the patients to the OR, we just take them into the hospital for a day, inject their wounds and then send them on their way,” Dr. Marinkovich said. Interim findings show that the patients have tolerated the therapy very well up to 52 weeks, he noted.
A greater percentage of wounds were healed by more than 50% following treatment with FCX-007 than those left untreated at weeks 4 (80% versus 20%), 12 (90% versus 44%), 25 (75% versus 50%), and 52 (83% versus 33%).
These results have been used to inform the design of the upcoming phase 3 study, DEFI-RDEB. The multicenter intrapatient randomized, controlled, open-label study is evaluating FCX-007 in the treatment of persistent nonhealing wounds in about 20 people with RDEB.
The promise of ‘off-the-shelf’ topical gene therapy
Another study Dr. Marinkovich is involved with is a phase 1/2 study of beremagene geperpavec (B-VEC), an “in-vivo” gene therapy. B-VEC is a topically administered therapy containing a replication-deficient, nonintegrating viral vector that contains two functional COL7A1 genes. The concept is that, when applied directly onto the skin, the virus gets into the skin and carries with it the healthy gene copies; these get taken up by the skin cells, which then produce COL7.
Initially, two patients with generalized severe RDEB were studied. B-VEC was applied to one of two wounds and a placebo to the other wound in each patient. Another four patients were then enrolled and studied for 3 months. Nine of 10 wounds closed completely after initial administration of B-VEC, with an average time to 100% wound closure of 17.4 days. The average duration of wound closure has been 113 days so far.
“One chronic wound that was originally open for over 4 years closed completely following B-VEC readministration. The wound has remained closed for 100 days,” Dr. Marinkovich and associates reported in a poster at the meeting. A postimaging study showed that COL7 was being produced from 48 hours to up to 90 days later.
“I’m really excited about this type of therapy,” Dr. Marinkovich said during an oral presentation. Unlike the ex-vivo gene therapy approach, where each patient’s cells have to be taken by a biopsy, altered, engineered, and expanded, which takes specialized facilities that can vary by country and location, this in-vivo gene therapy can be considered an “off-the shelf” treatment that can be shipped all over the world and could reach many patients. “It’s another weapon in our armamentarium against this deadly disease that we are all fighting against together,” Dr. Marinkovich added.
EBGRAFT is supported by Cure EB. The VIITAL trial is sponsored by Abeona Therapeutics. The phase 1/2 trials of EB-101 were funded by grants from the National Institutes of Health, EB Research Partnership, EM Medical Research Foundation, and Abeona Therapeutics. The FCX-007 phase 1/2 study was supported by Fibrocell Technologies. The upcoming phase 3 will be funded by Fibrocell Technologies in collaboration with Castle Creek Pharmaceuticals. The B-VEC study is supported by Krystal Biotech.
Dr. Uitto and Dr. McGrath had no potential conflicts of interest to report. Dr. Tolar has received funding from the National Institutes of Health, various EB charities and the Richard M. Schulze Family Foundation (RMSFF). He disclosed receiving honoraria or consultation fees from Ticeba/RHEACELL GmbH and Taiga Biosciences. Dr. Marinkovich disclosed being an investigator working on RDEB-related research projects in collaboration with Krystal Biotech, Fibrocell Technologies, Abeona Therapeutics, and Wings (formerly ProQR).
SOURCES: Gorell E et al. EB 2020, Poster 124; Marinkovich MP et al. EB 2020, Poster 123; Marinkovich MP et al. EB 2020, Poster 52.
LONDON – .
“I think there is a palpable sense that we are close to some breakthroughs for EB,” which may include “a cure for this intractable disease,” said Jouni Uitto, MD, PhD, in welcoming delegates to the meeting, held in January 2020.
Dr. Uitto, professor of dermatology and cutaneous biology, and biochemistry and molecular biology, at Sidney Kimmel Medical College, Philadelphia, said that the “breadth of academia-based basic science has been tremendous over the past 3 decades. We can now identify 21 different genes harboring mutations associated with different EB phenotypes, and we have a pretty good understanding how those mutations actually explain the phenotypic spectrum of different forms of EB.”
Importantly, “there are now perhaps as many as a dozen different clinical trials that are in the early stages of trying to find a permanent cure for this disease,” Dr. Uitto said, with some that are looking at fixing the underlying defect once and for all, or at the very least, counteracting subsequent complications. “The spectrum varies from attempting to enhance wound healing to gene repair, gene replacement, protein replacement therapies, cell-based therapies. There is a whole spectrum of often complementary approaches that we believe will lead to a cure and treatment for this disease. We look forward to developing therapies which will be helpful to the benefit of all the patients with EB,” said Dr. Uitto, who is also chair of the department of dermatology and cutaneous biology at Sidney Kimmel Medical College.
EB research is gathering ‘momentum’
John McGrath, MD, professor of molecular dermatology, King’s College, London, chaired a session on the latest in cell manipulation research and made the following comment: “A few years ago, we were making progress, but we were chatting about a lot of the same things; but now, suddenly there seems to be momentum, re-energy, rediscovery, real progress.”
Dr. McGrath noted that gene and cell research, and preclinical development, were culminating in clinical trials and potentially products that could change the way clinicians thought about managing patients with EB. “That prospect of getting closer and closer to real treatments, and maybe even a cure” is becoming more of a reality, he said.
Dr. McGrath is also head of the genetic skin disease group at King’s College London, and an honorary consultant dermatologist at St. John’s Institute of Dermatology, part of the Guy’s and St. Thomas’ NHS Foundation Trust in London. He has been a principal investigator for clinical trials of fibroblast cell therapy and allogeneic intravenous mesenchymal stromal cells (MSCs) therapy.
“It has been a joy for me to see the benefits of those clinical trials. There is nothing like it as an investigator when you see an intervention make a difference to a patient,” Dr. McGrath said. “For me, it was just a real eye opener when I saw the skin changes in a child that received intravenous allogeneic MSCs. The skin changed dramatically, it went from red and inflamed to calm and pink, [giving a] first glimpse into something that might be reversible, treatable, not just papering over the cracks.”
Correcting the genetic defect
The most severe form of RDEB is caused by mutations in COL7A1, the gene for collagen type 7 (COL7), the major connective component of the skin, anchoring the epidermis to the dermis. Its absence results in skin that can be so fragile it has been likened to the wings of a butterfly and results in severe blistering after very little trauma.
There is a lot of research on how to correct the underlying genetic defect, either by replacing COL7A1 entirely, repairing the gene, or editing the gene so that COL 7 can be produced in situ and prevent the formation of wounds and heal those that might already be present.
“The excitement is obvious,” said Jakub Tolar, MD, PhD, professor in the department of pediatrics, blood and marrow transplantation, and dean of the University of Minnesota Medical School, Minneapolis, who chaired a session on gene and gene manipulation therapies. “If one can go and correct that information, it follows that everything else is going to be okay,” he said. “Only it’s not. I think that it’s pretty clear that more than gene correction is needed.”
Some of the approaches to replace the faulty gene discussed at the meeting involved taking skin biopsy samples from a healthy area of skin from a patient with RDEB, isolating specific skin cells (fibroblasts, keratinocytes, or both), transferring a healthy copy of the COL7A1 gene into those cells – then expanding the population to form sheets of cells that can be grafted onto the wounds of the same patient.
Clinical trials of gene therapy for RDEB
Clinical trials with these novel gene-corrected, tissue-engineered grafts have already started, including EBGraft, a phase 1/2 open, nonrandomized, proof-of-concept trial using genetically corrected sheets of fibroblasts and keratinocytes, conducted by Alain Hovnanian, MD, PhD, Necker-Enfants Malades Hospital in Paris, and associates.
Then there is the phase 3 VIITAL trial being conducted at Stanford (Calif.) University by Jean Tang, MD, PhD, and colleagues. Recruitment in this open trial, which will enroll 10-15 patients with RDEB, has just started. The aim of the study is to investigate the efficacy and safety of EB-101, an autologous cell therapy that corrects COL7A1 in keratinocytes.
Positive findings from a phase 1/2 study with EB-101 were presented in a poster at the meeting by Emily Gorell, DO, a postdoctoral medical fellow in dermatology, at Stanford University and her associates. The trial included seven patients with RDEB who were treated and followed for 3 to 6 years. Data from that study showed that there were no serious adverse events and 95% of patients’ wounds that were treated (36/38) were healed by at least 50%, based on an Investigator Global Assessment at 6 months. In comparison, none of the untreated wounds had healed by that time point. “There was evidence of C7 [collagen 7] restoration at 2 years in two participants,” and wound healing was associated with both reduced pain and itch, the investigators wrote in the poster.
Another approach to this so-called ‘ex-vivo’ gene therapy is to take the patient’s cells via a small skin biopsy, genetically modify them, expand the population of these modified cells, and then inject them back into the patient. This approach was described by Peter Marinkovich, MD, of the department of dermatology at Stanford University, during an oral presentation and in a poster at the meeting.
Dr. Marinkovich discussed the results of an ongoing phase 1/2 study in which six subjects with RDEB – five adults and one child – were treated intradermally with genetically modified fibroblasts in a preparation currently known as FCX-007.
“Before we had to graft the cells, take the patients into the OR [operating room], with the risks of general anesthesia, but here we don’t have to take the patients to the OR, we just take them into the hospital for a day, inject their wounds and then send them on their way,” Dr. Marinkovich said. Interim findings show that the patients have tolerated the therapy very well up to 52 weeks, he noted.
A greater percentage of wounds were healed by more than 50% following treatment with FCX-007 than those left untreated at weeks 4 (80% versus 20%), 12 (90% versus 44%), 25 (75% versus 50%), and 52 (83% versus 33%).
These results have been used to inform the design of the upcoming phase 3 study, DEFI-RDEB. The multicenter intrapatient randomized, controlled, open-label study is evaluating FCX-007 in the treatment of persistent nonhealing wounds in about 20 people with RDEB.
The promise of ‘off-the-shelf’ topical gene therapy
Another study Dr. Marinkovich is involved with is a phase 1/2 study of beremagene geperpavec (B-VEC), an “in-vivo” gene therapy. B-VEC is a topically administered therapy containing a replication-deficient, nonintegrating viral vector that contains two functional COL7A1 genes. The concept is that, when applied directly onto the skin, the virus gets into the skin and carries with it the healthy gene copies; these get taken up by the skin cells, which then produce COL7.
Initially, two patients with generalized severe RDEB were studied. B-VEC was applied to one of two wounds and a placebo to the other wound in each patient. Another four patients were then enrolled and studied for 3 months. Nine of 10 wounds closed completely after initial administration of B-VEC, with an average time to 100% wound closure of 17.4 days. The average duration of wound closure has been 113 days so far.
“One chronic wound that was originally open for over 4 years closed completely following B-VEC readministration. The wound has remained closed for 100 days,” Dr. Marinkovich and associates reported in a poster at the meeting. A postimaging study showed that COL7 was being produced from 48 hours to up to 90 days later.
“I’m really excited about this type of therapy,” Dr. Marinkovich said during an oral presentation. Unlike the ex-vivo gene therapy approach, where each patient’s cells have to be taken by a biopsy, altered, engineered, and expanded, which takes specialized facilities that can vary by country and location, this in-vivo gene therapy can be considered an “off-the shelf” treatment that can be shipped all over the world and could reach many patients. “It’s another weapon in our armamentarium against this deadly disease that we are all fighting against together,” Dr. Marinkovich added.
EBGRAFT is supported by Cure EB. The VIITAL trial is sponsored by Abeona Therapeutics. The phase 1/2 trials of EB-101 were funded by grants from the National Institutes of Health, EB Research Partnership, EM Medical Research Foundation, and Abeona Therapeutics. The FCX-007 phase 1/2 study was supported by Fibrocell Technologies. The upcoming phase 3 will be funded by Fibrocell Technologies in collaboration with Castle Creek Pharmaceuticals. The B-VEC study is supported by Krystal Biotech.
Dr. Uitto and Dr. McGrath had no potential conflicts of interest to report. Dr. Tolar has received funding from the National Institutes of Health, various EB charities and the Richard M. Schulze Family Foundation (RMSFF). He disclosed receiving honoraria or consultation fees from Ticeba/RHEACELL GmbH and Taiga Biosciences. Dr. Marinkovich disclosed being an investigator working on RDEB-related research projects in collaboration with Krystal Biotech, Fibrocell Technologies, Abeona Therapeutics, and Wings (formerly ProQR).
SOURCES: Gorell E et al. EB 2020, Poster 124; Marinkovich MP et al. EB 2020, Poster 123; Marinkovich MP et al. EB 2020, Poster 52.
REPORTING FROM EB 2020