Enrollment has completed for the phase 3 GEM-3 study for beremagene geperpavec for patients with dystrophic epidermolysis bullosa. Topline results are anticipated before the end of 2021.
Krystal Biotech has completed enrollment in the phase 3 GEM-3 study, which is exploring the topical gene therapy beremagene geperpavec (B-VEC) as a treatment for patients with dystrophic epidermolysis bullosa (DEB). According to a statement from the company, the trial has accrued 31 patients and topline results are anticipated before the end of 2021.
“Completion of enrollment in the GEM-3 study marks a significant milestone for us,” Suma Krishnan, founder and chief operating officer of Krystal Biotech, said in a statement. “We would like to extend our gratitude to the patients, caregivers, investigators and study staff who, through their commitment during an especially difficult year, have helped bring us closer to potentially providing an easy-to-use topical treatment that addresses the underlying cause of DEB.”
B-VEC transduces the functional human COL7A1 gene using an engineered herpes simplex virus 1 (HSV-1) vector. Mutations in the COL7A1 gene are an underlying cause of DEB. The gene has a role in pro-alpha1 production, which is involved in assembly of type VII collagen. The HSV-1 one platform developed by Krystal, known as STAR-D, is designed for topical administration as well as other key traits, including safe re-administration and the ability to transduce multiple genes.
The phase 3 GEM-3 trial is utilizing intrapatient randomization, wherein matching wounds were identified to be treated with either B-VEC or a matched topical gel placebo. The ages of enrolled patients fell between 1 and 44 years, with 61% being pediatric patients. Wound pairs for placebo or B-VEC fell into 3 size segments that were match with escalating doses of B-VEC. Treatment was administered weekly until the wound resolved and re-administration was allowed, if required.
The primary end point of the study was complete wound healing from baseline and compared between the B-VEC and placebo-treated wounds. Secondary and additional end points focus on pain, healing, time to wound closure, and duration of closure. Patients in the study are followed for 24 weeks after which there is a final 30 day follow up and the option to move to an open-label extension study.
Prior to the formation of the phase 3 study, B-VEC demonstrated promising findings in a phase 1/2 study that included 12 total patients with severe generalized DEB, with either recurring or chronic wounds. The number of repeat doses per wound ranged from 4 to 41. Analysis from baseline to day 97 showed expression and correct localization of type VII collagen by both NC1 and NC2 specific antibodies following treatment with B-VECE. Additionally, mature anchoring fibrils were visible at day 97.
At an 8-week assessment, 100% closure was achieved for 82.4% of B-VEC-treated wounds compared with none of the placebo-treated wounds (P = .0001). At 12-weeks, 100% wound closure was present for 64.3% of B-VEC-treated wounds compared with 14.3% of those in the placebo group (P = .0348). Ninety percent or greater wound closure was achieved in 85.7% of treated wounds compared with 14.3% in the placebo group (P = .0019).
Safety data from this study showed tolerability with both the first dose and subsequent repeat dosing. Another potentially related adverse events were deemed mild (n = 7) or moderate (n = 1) in severity. Overall, there were no signs of inflammation or irritation.
“We are encouraged by the results to date and believe that B-VEC has the potential to be a very convenient and elegant approach to treating recurring and chronic wounds for patients suffering from DEB, a debilitating disease that affects patients and their extended families,” Krishnan said when the final results were announced in 2019.
Based on the promise of B-VEC, the gene therapy has received a number of designations from the FDA, which are meant to facilitate and expedite its development. In 2019, the therapy received a Regenerative Medicine Advanced Therapy designation from the FDA, which has also granted the treatment fast track and orphan drug designations as well as a rare pediatric designation.