Due to manufacturing issues, the FDA delayed approval of topical gene therapy B-VEC

Krystal Biotech announced that the FDA has decided to postpone the PDUFA date for the Biologics License Application (BLA) for B-VEC for the treatment of dystrophic epidermolysis bullosa to May 19, 2023, following receipt of its manufacturing information document submitted on December 20, 2022, and recommends that instruction manual labeling discussions be held no later than April 20, 2023
.

The manufacturing information file submitted by Krystal Biotech includes additional information about the hardware element replaced in the enrichment step of the manufacturing process (without affecting processing parameters or product contact materials) and comparable data
supporting the usability of the component.

At the BLA late-cycle review meeting on December 15, 2022, FDA stated that it would not convene an advisory committee meeting for B-VEC and that B-VEC's BLA was not required to provide a risk assessment and mitigation strategy (REMS, a drug safety program that requires certain drugs with serious safety concerns to help ensure that the benefits outweigh the risks).

Dystrophic epidermolysis bullosa (DEB) is a rare and severe single-gene inherited skin disease caused by one or more mutations
in the COL7A1 gene, which codes for the type VII protein collagen (COL7).
This mutation causes the skin to lack the basement membrane structure that holds the dermis (inner layer of skin) and epidermis (outer layer of skin) together, making the patient's skin and mucosal tissue extremely fragile, causing blisters and tears
with slight friction or trauma.
Wounds in DEB patients often do not heal completely, further leading to skin infections and fibrosis, which can fuse fingers and toes and ultimately increase the risk of developing aggressive squamous cell carcinoma, which can be fatal
in severe cases.
There are currently no targeted therapies approved
globally.

B-VEC is a topical topical gene therapy based on herpes simplex virus type 1 (HSV-1) that aims to restore normal COL7 protein expression
by direct application to wound delivery COL7A1 gene.

Mechanism of action of B-CEC (Source: Krystal Biotech website)

Krish S.
Krishnan, chairman and CEO of Krystal Biotech, said, "While we are disappointed that this information change is considered a significant amendment, we have been working diligently with the FDA as it completes its review
of B-VEC's BLA.
We will continue to prepare for commercialization and strive to make the drug
available to DEB patients as soon as possible after B-VEC is approved.
“