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.