dm+d

Unassigned

New Medicines

Recessive dystrophic epidermolysis bullosa (RDEB)

Information

New molecular entity
Castle Creek
Castle Creek

Development and Regulatory status

None
None
Phase III Clinical Trials
Yes
May 22Castle Creek raises $112.8 million to advance novel gene therapies and expand its pipeline. The financing is expected to provide sufficient capital for the company to complete its PIII study and issue top-line results for FCX-007 [5].
May 19Also has rare paediatric disease designation for the treatment of RDEB [4].
May 19FDA awards Regenerative Medicine Advanced Therapy (RMAT) designation to dabocemagene autoficel for treatment of RDEB [4].
Jan 17Granted fast track status in US for treatment of RDEB [4].
Jun 14Granted orphan drug status in US for RDEB [4].

Category

An autologous dermal fibroblast genetically modified to express functional type VII collagen (COL7). Involves collection of small skin biopsies from patients, separation of tissue into its component cells and expansion of fibroblast cell lineage in culture. While expanding the fibroblast cells, a vector is introduced to the culture to deliver the COL7 gene to the cells ex vivo. The fibroblasts are then re-injected, and transgene expression can be induced by a topically applied activator ligand.
EB is a rare disease; it is estimated to affect 1 in 17,000 live births and there are around 5,000 people living with EB in the UK [1]. Dystrophic EB (DEB) can be mild or severe (dominant or recessive). The missing protein and fragility occurs below the basement membrane within the superficial dermis. 25% of all EB cases are dystrophic EB [2].
Recessive dystrophic epidermolysis bullosa (RDEB)
Intradermal

Trial or other data

Sep 21PIII DEFI-RDEB study has recruited 6 patients and is no longer recruiting; reason not stated. It is due to complete collection of primary outcome data (complete wound closure of the first wound pair (treated vs. control) in Feb 23 [3].
Sep 20PI/II study (NCT02810951) completes collection of primary outcome data, having enrolled 6 patients. Data released in Jan 20, show that 80% of the patients achieved completed wound healing after 12 weeks of administration vs. no wound healing observed in intra-patients matched non-treated wounds (0%) [3,4].
Jul 19PIII DEFI-RDEB (dermal fibroblasts-RDEB) trial to evaluate efficacy of dabocemagene autoficel for the treatment of recessive dystrophic epidermolysis bullosa starts (NCT04213261, FI-EB-002). Comparison of the proportion of dabocemagene autoficel treated and untreated matched wounds with complete wound closure at week 12 is a defined primary outcome of the trial. The open-label, controlled trial intends to enrol 15 to 20 patients in the US. Intra-subject randomized (paired wounds in each subject receive experimental treatment, FCX-007, or remain untreated). Up to three target wound pairs will be identified for each subject. Following pairing, target wounds will be randomly assigned as the treatment wound (FCX-007 is administered) or control wound. Subjects will receive intradermal injections of FCX-007 in each specified treatment wound in two or more treatment sessions. The first treatment session occurs at Day 1 and the second at Week 12/Month 3. Additional treatment sessions may occur at Week 24/Month 6 and Week 36/Month 9 when unclosed treatment wounds may be re-treated, and unclosed control wounds may be treated [3].
Jul 16PI/II trial evaluating the safety, C7 expression and the presence of anchoring fibrils resulting from dabocemagene autoficel, and efficacy through evidence of wound healing, in adult patients with recessive dystrophic epidermolysis bullosa starts (FI-EB-001; NCT02810951). The open-label single-arm trial is enrolling 12 patients in the US. In Phase I, a target of three adult subjects will be enrolled into Group A and a target of three adult subjects will be enrolled into Group B. In Phase II the study will target enrolling subjects (aged seven (7 years or older) to each arm, but will allow a disproportionate distribution of subjects between Group A and Group B to equal approximately 6 total subjects. All subjects will receive FCX-007 into one or more paired target wounds as well as to intact skin at least one time during the study with a possible second administration pending laboratory results. One wound in each target wound pair will be used as control for efficacy and safety evaluations. Primary outcome is safety and secondary outcome complete wound closure at 52 weeks [3].