Topical Gene Therapy B-VEC Improves Vision in Compassionate Use Program

Krystal Biotech's B-VEC was well-tolerated and the treated patient experienced significant improvement in visual acuity.

This article was previously published on our sister site, Ophthalmology Times.

Krystal Biotech's topical beremagene geperpavec (B-VEC) improved vision in a patient with dystrophic epidermolysis bullosa (DEB) with recurrent cicatrizing conjunctivitis who was treated in a compassionate use program, according to data presented at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting, held April 23-27, in New Orleans, Louisiana.

“DEB is a devastating disease with limited treatment options, and there is a substantial population of DEB patients with ocular complications for which treatment options are limited and often include surgery,” Alfonso L. Sabater, MD, PhD, assistant professor of Clinical Ophthalmology at the Bascom Palmer Eye Institute at the University of Miami Miller School of Medicine, said. “It is exciting to potentially advance a topical treatment for patients with ocular complications associated with DEB.”

Krystal Biotech noted that the data describes the first application of B-VEC to treat the ocular complications of a patient with DEB in a compassionate use program. The patient, who presented with cicatrizing conjunctivitis, received surgical symblepharon lysis with pannus removal in the right eye. In addition to routine post-surgical management, the patient's right eye was treated with B-VEC at regular intervals after surgery.

B-VEC, which is an investigational redosable gene therapy, is intended to deliver 2 copies of the COL7A1 gene. It is topical, non-invasive, and meant to be applied directly to DEB wounds. B-VEC is designed to address the fundamental disease-causing mechanism by providing the skin cells with the ability to make normal COL7 protein.

B-VEC has received fast track designation, rare pediatric disease designation, and regenerative medicine advanced therapy designation from the FDA for the treatment of DEB. The EMA has granted PRIority MEdicines (PRIME) eligibility to B-VEC for the treatment of DEB. Furthermore, both agencies have granted the gene therapy orphan drug designation.

The gene therapy was associated with full corneal healing by 3 months and significant visual acuity improvement from hand motion to 20/40 at 7 months, the latest time point of treatment effect evaluation. Treatment effect evaluation remains ongoing.

In terms of safety, the company noted that B-VEC was well tolerated. No drug-related adverse events (AE) have been observed. Two nondrug-related, serious AEs were reported:

  • Prolonged hospitalization due to complications post-gastrointestinal surgery.
  • Prolonged hospitalization due to complications post-esophageal dilation.

B-VEC treatment was not interrupted during either event.

Ocular complications are common in patients with DEB, with over half of the patients diagnosed with recessive DEB potentially affected. Typical ocular manifestations include corneal abrasion, as well as corneal scarring, pannus, eyelid ectropions and blisters.1,2 There are no specific FDA-approved treatment options for ocular manifestations of DEB.3

“Ocular complications impose a heavy burden on DEB patients," Suma Krishnan, the president of research & development at Krystal Biotech, said. "Based on this promising initial data, we plan to engage with regulatory authorities and explore how we can expand the utility of B-VEC to address this urgent need. We are also excited about the implications for our platform as this clinical data, together with ongoing preclinical studies evaluating intravitreal and subretinal routes of delivery to the eye, suggests significant potential to treat multiple ocular diseases with few or no treatment options.”

DEB is a rare and severe disease that affects the skin and mucosal tissues. It is caused by one or more mutations in a gene called COL7A1, which is responsible for the production of the protein type VII collagen (COL7) that forms anchoring fibrils that bind the dermis (inner layer of the skin) to the epidermis (outer layer of the skin). The lack of functional anchoring fibrils in DEB patients leads to extremely fragile skin that blisters and tears from minor friction or trauma. DEB patients suffer from open wounds, which leads to skin infections, fibrosis which can cause fusion of fingers and toes, and ultimately an increased risk of developing an aggressive form of squamous cell carcinoma which, in severe cases, can be fatal.

1. Tang JY, Marinkovich MP, Lucas E, et al. A systematic literature review of the disease burden in patients with recessive dystrophic epidermolysis bullosa. Orphanet J Rare Dis. 2021 Apr 13; 16(1): 175. doi: 10.1186/s13023-021-01811-7.
2. Tong L, Hodgkins PR, Denyer J, et al. The eye in epidermolysis bullosa. Br J Ophthalmol. 1999 Mar; 83(3): 323-6. doi:10.1136/bjo.83.3.323.
3. Chen VM, Mehta N, Robbins CC, et al. Anterior-segment spectral domain optical coherence tomography in epidermolysis bullosa. Ocul Surf. 2020 Oct; 18(4): 912-919. doi: 10.1016/j.jtos.2020.08.010
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