dm+d

Unassigned

New Medicines

Dominant and recessive dystrophic epidermolysis bullosa (DEB)

Information

New molecular entity
Krystal Biotech
Krystal Biotech

Development and Regulatory status

None
None
Phase III Clinical Trials
Yes
Nov 20Krystal Biotech announces intention to submit MAA to the EMA for epidermolysis bullosa in 2021 [8].
Mar 20Krystal intends to submit a biologics licence application to the FDA and a marketing authorisation application to the EMA for approval of B-VEC in the EU. No dates for these events are discussed in the latest annual report, but Krystal does not anticipate generating revenues from product sales for the next year. They state it could be several years, before it has a commercialised product candidate [7].
Mar 20Pivotal study anticipated to begin in 1H 20. Krystal will also initiate a clinical study in the EU in H2 20, if necessary. No plans for filing with regulatory agencies stated [6].
Jul 19Krystal Biotech announch plans to collaborate closely with the EMA and initiate a clinical trial in the EU in the upcoming months.[3]
Jul 19Bercolagene telserpavec was granted Orphan Medicinal Product Designation (OMPD) from EMA for the treatment of DEB in Europe in 2018.[3]
Jun 19Pivotal PIII trial for DEB planned in H2 2019. [2,3]
Jun 19Bercolagene telserpavec received Regenerative Medicine Advanced Therapy (RMAT) designation from the US FDA for epidermolysis bullosa. This was granted based on positive interim data from the PI/II GEM-1, GEM-2 studies. [3]
Mar 19European Medicines Agency (EMA) granted access to its PRIME (PRIority MEdicines) scheme for bercolagene telserpavec for the treatment of DEB based on data from GEM-1 study and non-clinical data. [3]
May 18Bercolagene telserpavec received fast track designation from the US FDA for the treatment of DEB.[3]

Category

Herpes simplex virus-1 vector (HSV-1) engineered to deliver functional human COL7A1 genes directly to the ps’ dividing and non-dividing skin cells via a topical gel formulation. Off-the shelf gene therpy product with low immunogenicity.[2]
Population studies are complicated by the fact that this is not a uniform disease but a wide number of diseases of varying severity. It is likely that many patients with the more mild forms of EB remain undiagnosed. It is thought to affect 1 in 17,000 births. Around 5,000 people are affected in the UK [1].
Dominant and recessive dystrophic epidermolysis bullosa (DEB)
Topical

Further information

Yes

Trial or other data

Nov 20Pivotal GEM-3 study of B-VEC in DEB expected to complete enrolment in early 2021. Top line data and BLA filing are anticipated in 2021, in line with prior guidance. Data from this trial will also form the basis of an MAA filing in the EU which is anticipated to occur shortly after the BLA filing [11].
Jul 20PIII GEM-3 study to evaluate the efficacy and safety of beremagene geperpavec for the treatment of patients aged 6 months or older with both recessive and dominant forms of dystrophic epidermolysis bullosa starts (NCT04491604). Primary outcome measure is complete wound healing determined by the investigator, as compared to baseline in beremagene geperpavec treated wounds versus placebo treated at weeks 20, 22 and 24. Secondary endpoints to be evaluated in the study include complete wound healing at Weeks 8, 10 and 12; the mean change in pain severity (using either a VAS or FLACC-R Scale) per primary wound site associated with wound dressing; the proportion of primary wound sites with =75% healing assessed via Canfield photography. The randomised, double-blind, intra patient placebo-controlled study intends to enrol 30 patients in the US (no UK sites) [9].
Feb 20PI/II GEM-1 study completes collection of primary outcome data [9].
Dec 19NCT03536143 - no UK trial sites [5]
Oct 19Krystal announces final update from the PI/II trial of bercolagene telserpavec. In PI, two (2) adult patients with severe generalized RDEB were enrolled in May 2018. In each patient, two (2) wounds with an approximate surface area of 10 cm2 were randomized to receive either topical B-VEC or placebo. In PII, four (4) patients (2 adults, ages 22 and 19, and two pediatric, ages 14 and 15) with severe generalized RDEB were enrolled in December 2018. Prior to dosing, three (3) wounds up to 20cm2 were selected from each patient and subsequently randomized to receive either B-VEC or placebo in a 2:1 (B-VEC:placebo) ratio. One of patients (age 19) voluntarily discontinued from the study after 30 days due to an inability to travel to the clinical site. With respect to the six (6) B-VEC-administered wounds from the patients that remained on-study, two (2) were categorized as chronic and four (4) as recurring based on patient reporting. Chronic wounds were defined as having remained open for greater than 12 weeks, while recurring wounds are less than 12 weeks old, and open and close spontaneously. As part of the PII study, a chronic wound that had not healed completely at the Day 90 timepoint was re-administered B-VEC. This wound was subsequently observed for approximately four (4) additional months. In addition, two new patients (ages 21 and 33) with severe generalized RDEB were enrolled in June 2019. Prior to dosing, two wounds were selected in each patient and were randomized to receive either B-VEC or placebo in a 1:1 (B-VEC:placebo) ratio. Patients were administered B-VEC every other day for two weeks, or until the wound closed completely. Patients returned to the clinic for monthly follow-ups including imaging, biopsies for molecular correction analyses, and safety assessments [10].
Jul 19Positive results announced from PII GEM-1/2 trial in pts with severe generalized (RDEB). Five out of 6 wounds treated with the therapy closed 100% during the trial. The remaining one had been a deep wound open for more than four years. It closed 35% at the 30-day measurements and 42% at the 90-day measurement. The average time to complete 100% wound closure on treated wounds was 23 days. Treatment was well tolerated with no adverse events reported.[4]
Dec 18In the GEM studies, having established the presence of type VII collagen (COL7) and anchoring fibrils in the PI portion of the trial and acknowledged by the FDA, the endpoints of the PII portion were revised toward a focus on clinical improvement (i.e. wound closure). [2-4]
May 18PI/II GEM-1/GEM-2 open-label, placebol-controlled trial (NCT03536143) initiated to evaluate the safety and efficacy of bercolagene telserpavecin pts with DEB . The trial enrolled 4 pts in the US. Prior to dosing, 3 wounds of up to 20cm2 were selected on each pt and subsequently randomised to receive either treatment or placebo in a 2:1 ratio. A total of 4 KB103-treated recurring wounds and two KB103-treated chronic wounds were included in the trial results. Primary efficacy measures were presence of functional COL7 expression, observation of NC1 and NC2 reactive anchoring fibrils and continued expression following repeat administration. [2-4]

Evidence based evaluations