Haemophilia B race heats up with Uniqure data

Padua gambit seems to have worked as new gene therapy looks the equal of Pfizer/Spark Therapeutics.

Trial Results

Uniqure’s second try at haemophilia B looks better than its first. The first three patients dosed with the new version of its gene therapy AMT-061 saw their factor IX levels rise to 31% of normal, on average, after six weeks' treatment. This looks close to results achieved with the Pfizer-partnered Spark Therapeutics project fidanacogene elaparvovec.

Use of the Padua variant of the gene encoding for factor IX, already employed by Spark Therapeutics, looks like the ticket to success, as the earlier Uniqure candidate AMT-060, which used wild-type genes, only managed to muster an equivalent figure of 7.2% in a high-dose group. Three patients is obviously a small number from which to draw conclusions, but it builds confidence as the phase III gets under way. Shares rose 33% in early trading today.

Small change

The trial was to confirm that AMT-061, which features two nucleotide substitutions from AMT-060, could be dosed at similar levels to AMT-060. As Uniqure was able to transfer its breakthrough therapy designation from the US FDA from AMT-060 to AMT-061, this was an important confirmatory step before beginning phase III.

Patients in the trial saw no loss of factor IX activity, and none reported a bleed or need to infuse factor-replacement therapy. No immunosuppressive therapy was needed, although one patient experienced a mild increase in liver enzyme levels; this resolved without additional treatment.

Use of the Padua variant has been linked to an eight to ninefold increase in factor IX expression. Spark’s fidanacogene elaparvovec (SPK-9001) managed to produce expression levels of 36% of normal 12 weeks after administration, which reduced annualised bleeding rates 97%.

Spark and Pfizer have already begun enrolling patients in their phase III trial. Thanks to the relatively minor revisions to its factor IX gene therapies, Uniqure has managed to bypass more extensive phase II work, so it remains competitive with the Spark/Pfizer project.

Pivotal point

Uniqure itself enrolled the first of 50 patients into the phase III Hope-B trial in June. This study features a six-month run-in, so the group says it will begin dosing with AMT-061 in early 2019.

However, there is another wild card in the haemophilia B space in the form of Sangamo Therapeutics' gene editing project SB-FIX. Sangamo has released little news about this since it got authorisation to begin dosing patients in the UK in February, so it might not figure in the immediate race to launch a gene therapy for haemophilia B.

Uniqure confirmed that it had a competitive-looking project. Living up to high expectations will be a bigger challenge, however. The sellside puts sales at $763m in 2024, according to EvaluatePharma’s consensus, 17 times those forecast for the Pfizer/Spark project. AMT-061 will need better performance in phase III to justify these kinds of numbers.

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