FDA clears Vyjuvek as first topical gene therapy

The FDA has approved Krystal Biotech’s gene therapy Vyjuvek for dystrophic epidermolysis bullosa (DEB), a rare genetic disease characterised by fragile skin that can split and blister even with minor mechanical friction.

It is the first US approval for a topical gene therapy, according to the regulator, which has said Vyjuvek (beremagene geperpavec) can be used to treat patients aged six months of over who have mutations in the collagen type VII alpha 1 chain (COL7A1) gene.

DEB is one of the more severe forms of the epidermolysis bullosa (EB) group – sometimes referred to as “the worst disease you have never heard of”. In severe cases, it can lead to internal blistering of the mouth, oesophagus, lower gastrointestinal tract, upper airway, and genitourinary tract.

Symptoms vary depending on the inherited form, with dominant DEB tending to be more mild, while recessive DEB is generally much more debilitating and can have fatal complications. Before now, the only treatment was palliative care.

Vyjuvek – which has been approved for both forms – uses a non-replicating Herpes simplex virus to deliver normal copies of the COL7A1 gene to wounds. According to the FDA, it causes local production of the COL7 molecules, which form long, thin bundles that anchor the epidermis and dermis layers of the skin together.

The therapy is mixed into a gel and applied in droplets to patients’ wounds once a week by a healthcare professional, a simple procedure that means it can be delivered easily even to patients who live far from specialised clinical centres.

In the 31-patient GEM-3 clinical trial, Vyjuvek or a placebo were applied to two wounds of roughly equal size on the body of each patient. With the gene therapy, 65% of wounds healed, compared to 26% of the placebo group.

Krystal Biotech said after the approval that the gene therapy would be launched sometime in the third quarter at a cost of $24,250 per vial. Assuming a typical expected use of around 26 vials per year, the annual cost will be $631,500 before discounts – in keeping with the typically high annual cost of therapies for rare diseases.

Patient organisation DEBRA of America estimates that more than 25,000 people in the UUS live with EB, with the cost of wound care supplies alone running to $10,000 per month in severe cases.

Krystal said it expects to start the procedure to file for EU approval in the latter half of the year, and hopes to be in a position to submit the therapy in Japan in 2025.

Shire (now part of Takeda) was also developing a treatment for DEB based on recombinant COL7 protein, which it acquired along with Lotus Tissue Repair a decade ago, as well as a dermal substitute called ABH001, but neither has made it through to regulatory approval. Another therapy developed by Amicus Therapeutics failed a phase 3 trial in 2017.

At the moment, other candidates have also made it into late-stage testing, including Amryt Pharma’s wound-healing gel AP101, which was rejected by the FDA last year, but is still being developed for EB.

Other candidates include Castle Creek Biosciences’ FCX-007 – based on genetically modified fibroblasts obtained from the subject’s own skin cells – and Abeona Therapeutics’ cell therapy EB-101, which uses keratinocytes harvested from patients that are then engineered to produce COL7.