All four patients with dystrophic epidermolysis bullosa (DEB) enrolled in a Phase 2 study testing the safety and efficacy of Krystal Biotech’s topical gene therapy candidate KB103 have received the treatment.
Results are expected to be known by mid-year.
The protein type 7 collagen (Col7) binds the two top layers of the skin, and its deficit results in blisters and wounds. Mutations in the Col7A1 gene encoding Col7 results in either non-working or insufficient levels of Col7, causing the skin blistering observed in DEB patients.
KB103 is a gene therapy candidate designed to deliver functional Col7 directly to the impacted cells with the help of a modified herpes simplex virus (HSV-1; this modified virus is unable to cause disease).
In the ongoing six-month study (NCT03536143; GEM-1), underway at Stanford University, KB103 or placebo were applied directly to skin wounds (topical administration) of four DEB patients, two adults and two children (age 5 or older).
Three chronic wounds of up to 20 cm2 in surface area were selected for treatment in each patient. Two were randomly chosen to be treated with KB103, while a placebo was used on the third wound.
Effective healing will be evaluated in terms of the time taken to close the wound, and the period for which it remains closed. The potential of KB103 in wound healing will be compared to that of placebo.
Changes in the healed wound surface from the start of the treatment (baseline), as well as compared to placebo, will also be assessed. Imaging will be used to observe and record wound healing.
Levels of Col7 delivered by KB103 and the presence of anchoring fibrils will also be monitored. Anchoring fibrils are made of Col7 and serve as an indicator of skin integrity.
Differences in patient-reported outcomes concerning pain and its severity — from pre- to post-treatment — are among secondary trial outcomes, and the investigator’s global assessment scale will be used to evaluate patients’ response to treatment.
“Results from the GEM-Phase 2 study in 1H 2019 will enable us to select our endpoints going into the pivotal study in the second half of 2019,” Suma Krishnan, founder and chief operating officer of Krystal Biotech, said in a press release.
Encouraging preliminary results from this trial were announced in October. The team reported that in two adults, ages 35 and 28, topical treatment with KB103 closed wounds in two weeks and they remained closed for at least 3.5 months. No safety issues were reported.
“We believe that 2019 has the potential to be a year of significant clinical progress toward the ultimate goal of bringing KB103 to patients and families devastated by DEB,” Krishnan concluded.
The U.S. Food And Drug Administration granted KB103 a fast-track designation as a potential DEB treatment in May 2018.