dm+d

Unassigned

New Medicines

Filsuvez Dystrophic and junctional epidermolysis bullosa (DEB and JEB)

Information

Filsuvez
New molecular entity
Amryt Pharma
Amryt Pharma

Development and Regulatory status

Approved (Licensed)
Approved (Licensed)
Not recommended for approval (Negative opinion)
Yes
Yes
Aug 22Approved in the UK for the treatment of partial thickness wounds associated with dystrophic and junctional epidermolysis bullosa in patients 6 months and older and granted an orphan drug status [18]
Jun 22Approved in EU for the treatment of partial thickness wounds associated with dystrophic and junctional Epidermolysis Bullosa (EB) in patients 6 months and older [17].
Apr 22Recommended for EU approval by CHMP for “treatment of partial thickness wounds associated with dystrophic and junctional epidermolysis bullosa (EB) in patients 6 months and older.” Filsuvez will be available as a gel for cutaneous use [16].
Feb 22FDA has issued a complete response letter for oleogel-S10. The company has been requested to submit additional confirmatory evidence of effectiveness for the gel in its use for epidermolysis bullosa. [15] The company remain committed to bringing the drug to market [15].
Jan 22The EMA has delayed a decision on Oleogel-S10 to hear from external epidermolysis bullosa experts before issuing an opinion. The EMA are now expected to issue a decision in March 2022. The FDA PDUFA date has also been pushed back until the end of February to buy time to review additional analyses [14].
Mar 21New Drug Application filed with the FDA. Filsuvez has Fast Track designation [13].
Mar 21Filed with the EMA [12].
Nov 20Amryt intent to launch Filsuvez in the US in Q4 2021, and in Europe in Q1 2022 [11].
Sep 20Amryt intend to file for regulatory approval Q1 2021 [10]
Apr 20Amryt has said the EASE trial will be concluded slightly earlier than anticipated against the backdrop of the coronavirus (COVID-19) outbreak; topline results are expected in Q3/Q4 2020 [9].
Dec 19Latest Amryt presentation indicates plans are still to aim for both EMA and FDA approval in 2021 [8].
May 19Amryt aim for EMA approval in 2021 [6].
Sep 18FDA approves investigational new drug (IND) application for oleogel S10 in Epidermolysis Bullosa [4].
Aug 18The FDA has granted a Rare Pediatric Disease designation for oleogel S10 for the treatment of Epidermolysis Bullosa [4].
Sep 17Amryt is currently conducting a pivotal PIII study in EB which, if successful, could result in Orphan Drug Approval in EB in both the US and Europe, with launch in 2019 [2].
Sep 17AP101 has Orphan Drug Designation as a treatment for EB in both Europe and the US [2].

Category

A gel containing 0.5‑1.0 g birch bark, including 84‑95 mg triterpenes. It is thought to work by modulating inflammatory mediators and stimulating keratinocyte differentiation and migration, thereby promoting wound healing and closure.
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].
Dystrophic and junctional epidermolysis bullosa (DEB and JEB)
Topical

Further information

Yes

Trial or other data

Sep 20Top-line data from PIII EASE trial (NCT03068780) shows that AP101 met its primary end point (proportion of patients with closed wound) versus control gel at day 45 [10].
Dec 19PIII EASE study (NCT03068780) is due to complete imminently (Dec 19) [7].
Jan 19Independent Data Monitoring Committee (IDMC) recommends continuation of pivotal PIII EASE trial with an increase of 48 patients in the study to achieve 80% statistical power. Topline results are expected in the second half of 2019 [5].
Jan 18PIII EASE study (NCT03068780) is still recruiting and expects to complete collection of primary outcome data in Sep 18 [3].
Apr 17The first patient was enrolled to EASE (NCT03068780) and the interim analysis readout is expected in H1 2018 with top-line data expected in H2 2018 [2].
Mar 17Amryt commences the pivotal PIII EASE trial, to examine AP101´s efficacy for EB patients. Adult and paediatric patients with EB are being enrolled into a randomised double blind placebo controlled trial. A total of 164 evaluable patients across approximately 32 sites in 15 countries will be treated for a 90-day blinded period. The proportion of patients with completely healed target wounds within 45 days will be evaluated as the primary endpoint. Secondary endpoints include the time to achieve wound healing and changes in pain and pruritus (itch) [2].
In the EASE trial, oleogel S10 demonstrated a statistically significant acceleration of target wound healing by day 45 vs control gel (p = 0.013), representing a 44% increase in target wound closure with oleogel S10 vs control gel [11].

Evidence based evaluations

EpisalvanAccelerated healing of partial thickness wounds

Information

Episalvan
New molecular entity
Amryt Pharma
Not Known

Development and Regulatory status

Licence withdrawn
Licence withdrawn
None
Sep 22Amryt request withdrawal of EU marketing authorisation as they have decided not to market the product in the EU for commercial reasons [11].
Jun 21No further developments at this time [10].
Sep 20EMA notes that Episalvan is available in only one EU country at present (not stated which one) [9].
Sep 20EU marketing authorisation renewed [9].
Nov 19Latest Amryt presentation indicates plans are still to aim for both EMA and FDA approval for epidermolysis bullosa in 2021 [8].
Dec 18Amryt is awaiting results of EASE study in epidermolysis bullosa (expected mid 2019) before deciding on launch plans for oleogel S10 [7].
Sep 17AP101 is also being developed for epidermolysis bullosa. Amryt has been focussing on another asset, Lojuxta, and established the commercial, medical and regulatory infrastructure required to support the commercialisation of Lojuxta across its licenced territories utilising affiliates, third party consultants and distributors. This infrastructure can also be leveraged to support additional products such as AP101 [6].
Apr 16Birken acquired by and becomes a subsidiary of Amryt Pharma [5].
Jan 16Approved in EU [4].
Nov 15Positive opinion in EU for the treatment of partial thickness wounds in adults [3].
Nov 14Filed in the EU. The submission includes results from the three PIII trials that have demonstrated a significantly faster wound healing with Oleogel-S10 compared to current standard of care consisting mainly of applying wound dressing materials [1].

Category

A gel containing 0.5‑1.0 g birch bark, including 84‑95 mg triterpenes. It is thought to work by modulating inflammatory mediators and stimulating keratinocyte differentiation and migration, thereby promoting wound healing and closure.
Split thickness skin graft donor sites and burn wounds are classed as partial thickness wounds (PTWs) and the repair mechanism for each of these wound types is believed to be the same [6].
Accelerated healing of partial thickness wounds
Topical

Trial or other data

Nov 14Several pre-clinical and clinical studies have shown that dry extract from birch bark accelerates wound healing and skin regeneration processes. Dry extract from birch bark transiently upregulates pro-inflammatory cytokines (e.g., IL-6) and cyclooxygenase-2 (COX-2) on gene and protein level. Dry extract from birch bark promotes keratinocyte migration and promotes keratinocyte terminal differentiation [1].
Dec 12Birken AG initiated a PIII trial to assess the efficacy and safety of oleogel S10 ointment and a non-adhesive dressing, in accelerating the wound healing of split thickness skin graft donor sites, intra-individually compared to a dressing alone (NCT01807650; EudraCT 2012-003390-26). The primary outcome measure is the intra-individual difference in time to wound closure between the wound halves treated with oleogel S10 or the control, over 2 to 4 weeks. Enrolment of 105 patients was completed in Aug 13, in Greece, Spain, France and Latvia [2].
Jul 12Birken AG initiated a PIII trial to assess the efficacy and safety of oleogel S10 ointment and a non-adhesive dressing, in accelerating the wound healing of split thickness skin graft donor sites, intra-individually compared to a dressing alone (NCT01657305; Eudra 2012-000777-23). The primary outcome measure is the intra-individual difference in time to wound closure between the wound halves treated with oleogel S10 or the control, over 2 to 4 weeks. The trial will enrol 130 patients in Germany, Finland and the Czech Republic [2].

Evidence based evaluations