Abeona takes on Amryt – and more importantly, Krystal

Three new epidermolysis bullosa therapies are approaching the US, and expectations vary wildly.

The impressive phase 3 results Abeona posted yesterday on its epidermolysis bullosa gene therapy EB-101 suggest that the group might make a splash in this intractable condition. But other groups, namely Krystal Biotech and Amryt Pharma, are closer to the market or already there. 

The former might be the real threat to Abeona: Krystal’s gene therapy also had strong results in phase 3, though questions around durability remain. Amryt’s topical therapy Filsuvez is sold in the EU but has recently suffered a price cut in Germany – a sharp contrast with Abeona, whose management said it would seek premium pricing for EB-101

Amryt has the most advanced of the current crop of EB projects. Filsuvez, also called Oleogel-S10, was approved in Europe in June on the back of the Ease trial, which showed that significantly more treated than sham patients had complete closure of the target wound within 45 days of treatment, give or take a week. Several secondaries, however, were missed, including the crucial measure of time to target wound closure over 90 days.

Filsuvez launched in its first European territory, Germany, in September, and almost immediately hit resistance from payers. In a note yesterday, Stifel analysts wrote that they expect an average price of €63,000 ($62,000) per year for the drug in Germany, a steep fall from the €104,000 they had pencilled in previously. They now forecast Filsuvez to make $2m in 2022, cutting this figure in half.

The situation is even worse in the US. The FDA knocked Filsuvez back in February, and Amryt has taken the risky path of challenging the agency. It expects to submit a formal dispute resolution this month.

A little gem

The phase 3 hit with Vyjuvek, Krystal’s gene therapy, received a rapturous welcome from the company’s shareholders last year, with Krystal’s stock more than doubling. The project delivers COL7A1 as does Abeona’s gene therapy. 

Data from the Gem-3 trial showed that at six months, 67% of Vyjuvek-treated wounds were completely healed, versus 22% of placebo-treated wounds. At three months, said figures were 71% and 20% respectively, suggesting that some treated wounds had reopened.

Durability of Vyjuvek’s effect – always a crucial point for a gene therapy – will be an issue for the FDA to consider, as will Krystal’s claim that the project is re-dosable. The agency will pronounce on approvability in February. Abeona says a decision on EB-101’s BLA could come roughly a year after this.

The fact that the pivotal trials of EB-101, Filsuvez and Vyjuvek used completely different endpoints makes cross-trial comparisons, always troublesome, all but impossible. Fortunately the next EB project scheduled to report phase 3 data, Precigen and Castle Creek’s D-Fi gene therapy, uses the same measure as Vyjuvek, which might allow some conclusions on relative efficacy and safety to be drawn.

One question that remains is whether the lower price for Filsuvez represents a floor for EB drugs. Should the gene therapies gain approval, higher pricing might be expected, particularly if their durability of effect allows one-time treatment. 

Yesterday Abeona said the data on EB-101, and particularly the project’s ability to decrease pain, had led it to re-examine its conclusions about what price it might be able to charge. That will be a decision for the payers – but the regulators must render their verdicts first.

Selected late stage products for epidermolysis bullosa
Project Company Mechanism Status 2028e EB forecasts ($m)
Filsuvez/Oleogel-S10 Amryt Pharma Topical betulin gel Approved in EU & UK based on Ease trial; received US CRL Mar 2022 but is appealing 235
Vyjuvek (B-Vec/beremagene geperpavec) Krystal Biotech Topical HSV-vectored COL7A1 gene therapy Pivotal Gem-3 trial hit Nov 2021; filed in US, Pdufa in Feb 17, 2023 636
Phase 3
EB-101 (prademagene zamikeracel) Abeona Therapeutics Autologous COL7A1 gene therapy (keratinocytes transduced with EB-101 then transplanted) Pivotal Viital trial hit Nov 2022; US filing planned Q2 2023, and approval decision expected Q1 2024 122
D-Fi (dabocemagene autoficel) (previously FCX-007) Precigen/Castle Creek Biosciences Autologous COL7A1 gene therapy, intradermal administration (lentiviral vector)  Pivotal DeFi-RDEB trial primary completion February 2023  -
Phase 2
Autologous Cultured Epidermal Grafts Holostem Terapie Avanzate RV-LAMB3-transduced epidermal stem cells Hologene 5 ongoing  -
BBP-589/PTR-01 Bridgebio Pharma/
Phoenix Tissue Repair
Intravenously-administered recombinant collagen 7 protein replacement therapy Phase 2 trial completed Sep 2021; no data reported as yet. Ph2 extension trial in 2 patients ongoing 61
Source: Evaluate Pharma, clinicaltrials.gov, company releases.

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