Rare Disease Report

Is New Treatment on the Horizon for Dystrophic Epidermolysis Bullosa?

APRIL 11, 2018
Krista Rossi
Krystal Biotech is currently working to develop “off-the-shelf” gene therapies to treat rare skin diseases.

The company’s lead product candidate, KB103, is the first-ever topical gene therapy for dystrophic epidermolysis bullosa (DEB). Last week, it was announced that an investigational new drug (IND) application was submitted for the potential therapy, just five months after it received an orphan drug designation from the U.S. Food and Drug Administration (FDA).

DEB, a debilitating genetic condition, causes the skin to be very fragile and blister easily—even from the slightest of injuries, like bumping or rubbing. The disease is caused by a mutation in the gene called COL7A1, when mutated, doesn’t produce the required protein collagen VII to create the anchoring fibers that hold the skin together.

The absence of these fibers causes lesions, which can sometimes develop cancer squamous carcinoma. It is also important to note that patients suffering from the recessive dystrophic or junctional form of epidermolysis bullosa are the ones at risk for developing cancer squamous carcinoma by age 35. Per published research, the median time to death for most DEB individuals that develop cancer squamous carcinoma is about 5 years.   

Krish Krishnan, CEO of Krystal Biotech, is well aware of the struggles facing this patient population, often referred to as “Butterfly Children.”

“Their entire lives are filled with parents or doctors bandaging all the wounds every day with specialty bandages. The entire process is incredibly painful and time consuming,” said Krishnan. “Not to mention, the sores often itch uncontrollably for these children, which causes them to scratch and traumatize the skin even more.”

“And not only do the kids suffer, obviously, the parents go through a lot, and unfortunately there are no treatments presently.”

The cost of treatment for patients with DEB is an ongoing issue for those who need care. “It is estimated that the global diagnosed market is about 7,000-7,500 patients maybe. But the cost of maintaining a patient today, since there’s no treatment, is somewhere between $250,000 and $400,000 a year, so not all parents, not all families can afford to do it.”

However, Krishnan believes that Krystal Biotech’s approach could potentially deliver a simple, effective, and painless way to treat the disease. Krystal Biotech’s approach use a modified herpes simplex (HSV-1) virus as a vehicle to deliver the missing or mutated COL7A1 gene to the patients.

“We settled on HSV-1 after researching many other alternatives because the ultimate goal of the company was to come up with a product that could be applied directly onto the skin and treat the disease. So we are working to formulate the modified virus into a gel and apply it directly to treat open wounds or administer the virus intradermally to treat closed wounds.” said Krishnan.

To date the focus of gene therapy has not been in HSV, a virus that has traditionally been ignored.

HSV-1 is inherently a non-integrating virus that has been modified by Krystal Biotech to also be non-replicating. So, functionally Krystal Biotech’s approach is closer to gene-delivery than “classic gene therapy” where the virus usually integrates with the DNA. This non-integrating nature of the HSV-1 virus could potentially make it more attractive than other viruses from a long-term safety perspective.”
 
If successful, this first-ever topical gene therapy for DEB could potentially lead to a domino effect with similar approaches to treat other skin diseases. “We hope to start with treating monogenic skin diseases and then move to using the same approach to treating broad dermatological indications.”

In terms of a timeline, Krishnan says to look for the new treatment in the near future. “We have a lot of work to do; the clinical data has to pan out. We are hopeful to file for approval on KB103 in 2020 and launch thereafter. However, should KB103 prove to be efficacious in the upcoming Phase 1/2 clinical trial, Krystal intends to work with the Agency and patient advocacy groups to pursue KB103 for compassionate or expanded use.”

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