KB103 Continues to Show Promise in Treating DEB, Receives RMAT Designation from FDA

KB103, Krystal Biotech‘s investigational topical gene therapy for treating dystrophic epidermolysis bullosa (DEB), continues to show promise in the treatment of skin wounds and has received the designation of regenerative medicine advanced therapy (RMAT) from the U.S. Food and Drug Administration (FDA).

DEB is a rare and incurable form of epidermolysis bullosa (EB), a genetic skin disorder in which the patients’ skin blisters and tears easily, causing painful wounds and scarring. DEB is caused by genetic mutations in the COL7A1 gene, which provides instructions to make a protein called type 7 collagen (COL7) that is essential to maintain healthy skin.

KB103 is a topical gene therapy candidate that has been designed to prevent skin blistering. It works by delivering a normal version of the COL7A1 gene directly to skin cells of DEB patients, using a modified version of the herpes simplex virus.

The RMAT designation from the FDA comes shortly after KB103 received the PRIME (PRIority MEdicine) designation from the European Medicines Agency (EMA).

The RMAT designation is attributed to new cell or gene therapies whose main purpose is to treat medical conditions considered extremely serious or life-threatening, or when they show significant clinical improvements over existing therapies. As with the FDA’s breakthrough therapy designation, cell or gene therapies that receive the RMAT designation may be eligible for priority review and accelerated approval.

The new designation was based on data from the ongoing GEM-1 Phase 1/2 clinical trial (NCT03536143), assessing the wound-healing effects and safety profile of KB103 in a group of DEB patients.

The very small trial was divided into two phases: an initial proof-of-concept phase in which KB103 was shown to restore COL7; and a second patient-dosing phase, in which the safety and effectiveness of the treatment was evaluated in a group of DEB patients.

In December 2018, during the second phase of the trial, four patients with severe generalized recessive DEB (RDEB) — two adolescents 14 and 15 years old, and two adults 19 and 22 — were enrolled in the study.

Prior to dosing, three chronic wounds covering an area of up to 20 cm² (20 square centimeters) were selected for treatment on each patient. Two were chosen randomly to be treated with KB103, and the third with a placebo. Treatment was applied topically to wounds during the first five days, and then again at days 30, 60, and 90, if the wound was still visible.

One of the patients dropped out of the trial due to inability to travel to the clinical trial site. The final analysis of the Phase 2 data of the trial was performed based on the remaining three patients, corresponding to six KB103-treated wounds (two chronic and four recurring) and three placebo-treated wounds. Of note, chronic wounds are those that do not heal for more than 12 weeks, while recurring wounds are those that open and close spontaneously.

The two adult RDEB patients whose wounds (two wounds with an area of 10 cm² on each patient) were treated with KB103 or a placebo during the first phase of the trial, also were included in the analyses.

Key findings from both phases of GEM-1 showed that:

• at day 90, KB103 was considered safe and well-tolerated by patients; no serious adverse side effects, drug-related side effects, inflammation, irritation or undesirable immune system responses were reported during the trial;
• seven out of the eight wounds treated with KB103 during both phases of the trial healed completely;
• none of the placebo-treated wounds healed completely over the course of the study;
• on average, KB103-treated wounds during both phases of the study took 20.14 days to heal;
• on the two patients who participated in the first phase of the trial, healed wounds remained closed for at least 184 days (6.6 months) and 174 days (6.2 months), which was the time of last follow-up;
• tissue biopsy analysis confirmed that functional COL7 was present in the skin of patients treated with KB103.

“New treatments for patients suffering from EB are desperately needed, especially one that provides a convenient, painless way to administer treatment for patients suffering with this debilitating disease and to reduce their travel burden,” Peter Marinkovich, MD, associate professor of dermatology at Stanford University and principal investigator in the GEM study, said in a press release.

“These exciting data in the Phase 1/2 trials are supportive of this very promising new approach for treating this debilitating disease,” Marinkovich added.

Krystal Biotech is planning to launch a Phase 3 pivotal trial before the end of this year, in which the company is planning to study in more detail the effects of KB103 on the treatment of chronic wounds.

Two additional patients already started treatment in the Phase 1/2 trial with more frequent dosing, in preparation for that trial. Krystal assured it will provide an additional update on these patients before the start of the trial.