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Recombinant factor VIII safe and effective in PUPs A-LONG study

Presented by
Dr Christoph Königs, University Hospital Frankfurt, Germany
ISTH 2020
Phase 3, PUPs A-LONG

In the first prospective study of an extended half-life recombinant factor VIII (rFVIII) treatment for previously untreated patients with severe haemophilia A, rFVIII was well tolerated. Promisingly, the high-titre inhibitor rate was lower than that seen in the literature [1].

The development of alloantibody inhibitors that interfere with prophylaxis and treatment is the largest safety concern in infants with severe haemophilia A, as it occurs in up to 37% of the infant population. Recombinant FVIII products offer a technological solution by reducing the risk of formation of alloantibody inhibitors against FVIII, as well as prolonging the half-life of the protein.

The open-label, single-arm, multicentre, phase 3 PUPs A-LONG study investigated the safety and efficacy of rFVIII prophylaxis in previously untreated patients with severe haemophilia A, who were all male and under the age of 6. Of the 103 patients who received at least 1 dose, 80 were below 1 year old, 20 had a positive family history of inhibitors, and 82 had high-risk haemophilia genotype. The study was completed by 84.5% of the participants. Episodic treatment was started by 81 participants; of these, 69 switched to prophylaxis. Another 20 patients were on prophylaxis from the beginning. The primary endpoint of the study was inhibitor development, and a secondary endpoint was the annualised bleeding rate (ABR).

In total, 31.1% of the participants developed inhibitors, and 15.6% developed high-titre inhibitors (≥5 BU/mL). Median time to inhibitor development was 9 exposure days (range 1-53 days). A treatment-related serious adverse event was seen in 27.2% of participants. One patient died due to an intracranial haemorrhage, which happened during the screening period prior to the first dose of the medication and was therefore not treatment related.

The authors concluded that the inhibitor rate seen in this study was in the expected range, but high-titre incidence was lower than that reported in the literature.

1          Königs C, et al. OC 03.2, ISTH 2020 Virtual Congress, 12-14 July.

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