Vyjuvek (beremagene geperpavec-svdt) / Krystal Biotech - LARVOL DELTA

Clinical characteristics of recessive dystrophic epidermolysis bullosa patients with collagen VII antibodies (SID 2025) - "Certain therapies may induce host production of C7 such as gentamicin, exon skipping, and beremagene geperpavec, or patients may be exposed to exogenous C7 such as gene-corrected grafting, intravenous recombinant C7, and bone marrow transplantation. The pathogenicity of these antibodies and their impact on therapy response in RDEB patients remains unclear and warrants further evaluation. Importantly, understanding C7 antibodies may assist future therapeutic research in RDEB patients."

Clinical • Bone Marrow Transplantation • Gene Therapies

Expansion of an HSV-1-based gene therapy platform to treat Hailey-Hailey and Darier diseases (SID 2025) - "The herpes simplex virus type 1 (HSV-1)-based gene therapy beremagene geperpavec (B-VEC) has been successful in treating the rare genetic skin blistering disease dystrophic epidermolysis bullosa (DEB)...Twenty-four hours after administration, skin punches were taken for DNA and RNA quantification, IF, and hematoxylin and eosin staining. In vitro and in vivo analyses indicated that both KB111 and KB112 are capable of transducing keratinocytes and expressing their encoded ATPases with minimal toxicity both in culture and in murine skin, demonstrating that Krystal's HSV-1-based platform is well-suited for the treatment of both HHD and DD."

Gene therapy • Dermatology • Gene Therapies • Genetic Disorders • Herpes Simplex

A randomized controlled trial of a novel skin substitute on epidermolysis bullosa wounds (SID 2025) - "The topical drugs, beremagene-geperpavec and birch-triterpenes, have been approved for RDEB wound healing but are not curative...No AEs were related to Spincare® and its discontinuation. Results from this pilot trial show that Spincare matrix treatment on RDEB wounds is a safe and tolerable cell therapy delivery method for a future Phase 1 trial of gene-edited induced pluripotent stem cells."

Clinical • Anemia • Dermatology • Hematological Disorders • Infectious Disease • Oncology • Pain • Squamous Cell Carcinoma

A Targeted Literature Review of Value-Based Agreements (VBAs) for Cell and Gene Therapies in the United States (ISPOR 2025) - "The therapies with VBAs in place included: Beqvez, Casgevy, Hemgenix, Kymriah, Luxturna, Lyfgenia, Roctavian, Vyjuvek, Zolgensma, and Zynteglo... In this review, multiple VBAs for CGTs were identified across multiple disease areas. Most payers did not publicly disclose which outcomes measures the VBAs were assessing. Of those that did, outcomes assessed could be sourced from routine patient visits and/or adjudicated claims, placing no additional burden on providers to collect data for the sole purpose of the VBA."

Gene therapy • Review • Gene Therapies

Deconstructing FDA's Expedited Program Determinations: Analyzing how the Agency may Set the Bar for RMAT Designation (ASGCT 2025) - "Parexel explored the relationship between the early-phase data from press releases around the time of RMAT designation and pivotal data from FDA review memos for marketing applications for two cases of RMAT-designated gene therapies, VYJUVEK (beremagene geperpavec) and BEQVEZ (fidanacogene elaparvovec-dzkt), that were approved in 2023 and 2024. Conducting analyses, such as the one listed above, that contextualize the RMAT-designation supporting data within the totality of publicly disclosed information for that development program, can help inform developers in making decisions about the amount of evidence and timing for submission of RMAT designation requests. Disease Focus of Abstract:Other Other: Rare Disease"

Gene Therapies • Hematological Disorders • Hemophilia • Hemophilia B • Rare Diseases

Krystal Biotech Announces First Quarter 2025 Financial and Operating Results (GlobeNewswire) - "$88.2 million in 1Q VYJUVEK revenue and $429.4 million since launch in Q3 2023...VYJUVEK (beremagene geperpavec-svdt, or B-VEC) for the Treatment of Dystrophic Epidermolysis Bullosa (DEB)...The Company continues to expect a decision by Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) on its Japan New Drug Application (JNDA) in 2H 2025...The Company continues to enroll Cohort 3 of CORAL-1, the Company’s multi-center, dose escalation study evaluating KB407 in patients with CF...The Company received full sanctioning of the study protocol by the Cystic Fibrosis Foundation Therapeutic Development Network in January and remains on track for an interim molecular data readout for Cohort 3 patients in mid-2025...The Company continues to enroll in Cohort 2 and is working to enroll in Cohort 3 of SERPENTINE-1....The Company expects to report molecular results for the additional Cohort 2 and 3 patients later this year."

Enrollment status • Japan approval • P1 data • Sales • Alpha-1 Antitrypsin Deficiency • Cystic Fibrosis • Dermatology • Genetic Disorders

Krystal Biotech Announces European Commission Approval of VYJUVEK for the Treatment of Dystrophic Epidermolysis Bullosa (GlobeNewswire) - "Krystal Biotech, Inc...announced today that on April 23, 2025, the European Commission (EC) granted marketing authorization to VYJUVEK (beremagene geperpavec-svdt) for the treatment of wounds in patients with dystrophic epidermolysis bullosa (DEB) who have mutations in the collagen type VII alpha 1 chain (COL7A1) gene, starting from birth....This EC decision authorizes the marketing of VYJUVEK in all European Union member states, as well as Iceland, Norway and Liechtenstein....The Company is planning for its first European launch in Germany in mid-2025....The EC approval follows the positive recommendation issued by the European Medicines Agency’s Committee for Medicinal Products for Human Use in February and was based on a comprehensive clinical dataset including results from the Company’s Phase 1/2 GEM-1 and Phase 3 GEM-3 studies..."

EMA approval • Launch Europe • Dermatology • Genetic Disorders

Impact of COL7A1 Gene Therapy on SCC Recurrence in RDEB Skin (clinicaltrials.gov) - P2 | N=16 | Recruiting | Sponsor: Stanford University | Not yet recruiting ➔ Recruiting

Enrollment open • Gene Therapies • Oncology • Squamous Cell Carcinoma

Long-Term Safety and Tolerability of Beremagene Geperpavec-svdt (B-VEC) in an Open-Label Extension Study of Patients with Dystrophic Epidermolysis Bullosa. (PubMed, Am J Clin Dermatol) - P3 | "Patients undergoing extended B-VEC treatment maintained high satisfaction and continued to respond to treatment with no new safety signals detected in the open-label extension study, supporting the continuous use of B-VEC."

Journal • Gene Therapies • Herpes Simplex • COL7A1

VYJUVEK for Dystrophic Epidermolysis Bullosa: Ethical Dilemmas in Access and Pricing. (PubMed, J Am Acad Dermatol) - No abstract available

Journal • Pricing • Dermatology

Beremagene Geperpavec is the First FDA-Approved Topical Gene Therapy for Dystrophic Epidermolysis Bullosa (AAD 2025) - "Serious adverse events, not believed to be directly related to B-VEC, included hospitalizations for diarrhea, severe anemia, cellulitis, and infection related to a hemodialysis catheter. While there are no comparator trials with other therapies, B-VEC has been shown to be a safe and effective treatment for DEB in patients 6 months and older."

Gene therapy • Anemia • Dermatology • Gene Therapies • Hematological Disorders • Infectious Disease • Oncology • Pruritus • Squamous Cell Carcinoma • COL7A1

Krystal Biotech Receives Positive CHMP Opinion for VYJUVEK for the Treatment of Dystrophic Epidermolysis Bullosa (GlobeNewswire) - "Krystal Biotech, Inc...today welcomed the European Medicines Agency's (EMA’s) announcement that its Committee for Medicinal Products for Human Use (CHMP) has issued a positive recommendation for the European Commission (EC) to approve VYJUVEK (beremagene geperpavec-svdt, or B-VEC) for the treatment of wounds in patients with dystrophic epidermolysis bullosa (DEB) who have mutations in the collagen type VII alpha 1 chain (COL7A1) gene, starting from birth...The final EC decision is anticipated in the second quarter of 2025...The positive opinion issued by the CHMP is based on a comprehensive clinical dataset including results from the Company’s Phase 1/2 GEM-1 and Phase 3 GEM-3 studies..."

CHMP • EMA approval • Dermatology • Genetic Disorders

Impact of COL7A1 Gene Therapy on SCC Recurrence in RDEB Skin (clinicaltrials.gov) - P2 | N=16 | Not yet recruiting | Sponsor: Stanford University

Gene therapy • New P2 trial • Gene Therapies • Oncology • Squamous Cell Carcinoma

Estimating Costs in Beremagene Geperpavec for Dystrophic Epidermolysis Bullosa-Reply. (PubMed, JAMA Dermatol) - No abstract available

Journal

Estimating Costs in Beremagene Geperpavec for Dystrophic Epidermolysis Bullosa. (PubMed, JAMA Dermatol) - No abstract available

Journal

Practical considerations relevant to treatment with the gene therapy beremagene geperpavec-svdt for dystrophic epidermolysis bullosa. (PubMed, J Dermatolog Treat) - "This review discusses the burden of disease, describes the clinical trial outcomes of B-VEC, and provides physician and patient/caregiver recommendations as a practical guide for the real-world use of B-VEC, which can be administered in-office or at the patient's home. By continuing to optimize the practical aspects of B-VEC administration, the focus will continue to shift to patient-centric considerations and improved patient outcomes."

Gene therapy • Journal • Review • Dermatology • Gene Therapies • Herpes Simplex • COL7A1

Exploring the Financial Burden Associated with the Management of Dystrophic Epidermolysis Bullosa (DEB): A Systematic Literature Review (SLR) with Database Review of Future Disease-Modifying Therapies (DMTs) (ISPOR 2024) - "Nine clinical trials research 7 potential DMTs: advanced/gene therapies (EB-101, B-VEC, ALLO-ASC-SHEET, FCX-007), protein-replacement therapies (PTR-01, PTR-01-002), and a proteinase inhibitor (Polyphenon E). Previously, as there were no DMT options for patients with DEB treatment was symptomatic only. Future innovative DMTs should aim to prevent skin wounds, thereby decreasing the need for hospitalization and outpatient visits."

Review • Dermatology • Gene Therapies

Long-Term Safety and Efficacy of Beremagene Geperpavec (B-VEC) in an Open-Label Extension Study of Patients with Dystrophic Epidermolysis Bullosa (AAD 2024) - No abstract available

Clinical • Late-breaking abstract

Emerging Gene Therapeutics for Epidermolysis Bullosa under Development. (PubMed, Int J Mol Sci) - "The clinically more advanced gene replacement strategy was successfully applied in severe EB forms, leading to a ground-breaking in vivo gene therapy product named beremagene geperpavec (B-VEC) recently approved from the US Food and Drug Administration (FDA). In addition, the continuous innovations in both designer nucleases and gene editing technologies enable the efficient and potentially safe repair of mutations in EB in a potentially permanent manner, inspiring researchers in the field to define and reach new milestones in the therapy of EB."

Gene therapy • Journal • Review • Gene Therapies • Genetic Disorders

Ocular Gene Therapy in a Patient with Dystrophic Epidermolysis Bullosa. (PubMed, N Engl J Med) - "Beremagene geperpavec (B-VEC) is a replication-deficient herpes simplex virus type 1-based gene therapy engineered to deliver functional human type VII collagen. Here, we report the case of a patient with cicatrizing conjunctivitis in both eyes caused by dystrophic epidermolysis bullosa who received ophthalmic administration of B-VEC, which was associated with improved visual acuity after surgery."

Gene therapy • Journal • Conjunctivitis • Gene Therapies • Genetic Disorders • Herpes Simplex • Ocular Infections • Ocular Inflammation • Ophthalmology

Krystal Biotech Announces Publication in the New England Journal of Medicine on the Application of B-VEC to Treat Ocular Complications in Patient with Dystrophic Epidermolysis Bullosa (GlobeNewswire) - "Krystal Biotech, Inc...today announced data on the compassionate use of beremagene geperpavec (B-VEC), administered as an eyedrop to treat a patient with dystrophic epidermolysis bullosa (DEB) with cicatrizing conjunctivitis has been published in the New England Journal of Medicine (NEJM)....A patient presented with severe cicatrizing conjunctivitis secondary to DEB. Surgical symblepharon lysis of the patient’s right eye with pannus removal was conducted and regular administration of B-VEC as an eyedrop directly to the eye (5×10⁹ PFU/mL) were added to routine post-surgical care, three times weekly for the first two weeks and then once weekly. B-VEC application frequency was further decreased to once monthly once the corneal epithelium was healed. B-VEC was well tolerated and associated with full corneal healing by 3 months as well as significant visual acuity improvement from hand motion to 20/25 at 8 months."

Clinical data • Dermatology

Estimated Spending on Beremagene Geperpavec for Dystrophic Epidermolysis Bullosa. (PubMed, JAMA Dermatol) - "Estimated lifetime total costs per patient were $15 million (range, $10 million-$20 million) per patient with autosomal recessive DEB and $17 million (range, $11 million-$22 million) for patients with autosomal dominant DEB. Results of this economic evaluation suggest that the FDA's broad indication for the use of B-VEC in treating both autosomal recessive and autosomal dominant DEB will have significant implications for payers."

Journal • Gene Therapies • Rare Diseases

Management of Skin Lesions in Patients with Epidermolysis Bullosa by Topical Treatment: Systematic Review and Meta-Analysis. (PubMed, Healthcare (Basel)) - "Additionally, evidence indicates significant progress in gene therapies (B-VEC), as well as cell and protein therapies. The dressing group, Oleogel S-10, allantoin and diacerein 1%, were the most represented, followed by fibroblast utilisation. In addition, emerging treatments that improve the patient's innate immunity, such as calcipotriol, are gaining attention. However, more trials are needed to reduce the prevalence of blistering and improve the quality of life of individuals with epidermolysis bullosa."

Journal • Retrospective data • Review • Dermatology • Gene Therapies • Infectious Disease • Pain • Pruritus

Revolutionary breakthrough: FDA approves Vyjuvek, the first topical gene therapy for dystrophic epidermolysis bullosa. (PubMed, Ann Med Surg (Lond)) - "Clinical trials have shown that Vyjuvek increases the probability of complete wound healing compared to placebo. Although further research is needed, Vyjuvek represents a significant advancement in addressing the unmet medical needs of patients with DEB, offering hope for improved quality of life and long-term complication reduction."

FDA event • Gene therapy • Journal • Gene Therapies • Genetic Disorders • Herpes Simplex

Current Treatment Landscape for Dystrophic Epidermolysis Bullosa: From Surgical Management to Emerging Gene Therapies and Novel Skin Grafts. (PubMed, J Hand Surg Am) - "One of these treatments, B-VEC, is an HSV-1-based topical gene therapy designed to restore collagen 7 by delivering the COL7A1 gene, leveraging a differentiated HSV-1 vector platform that evades the patient's immune system response. Other work has been performed to retrovirally modify autologous keratinocytes, but limitations of this process include increased labor in harvesting and engineering autologous cells. This article provides an overview of DEB treatment with an emphasis on emerging gene therapies and novel skin grafts, especially as they pertain to pseudosyndactyly treatment."

Gene therapy • Journal • Review • Alopecia • Corneal Abrasion • Dermatology • Gastrointestinal Disorder • Gene Therapies • Immunology • Mood Disorders