Treatment with Eloctate (efmoroctocog alfa) was well-tolerated and effective at preventing and treating bleeding episodes in children with severe hemophilia A who had never received any form of therapy for their disease, a Phase 3 trial shows.
The study had enrolled boys with severe hemophilia A younger than age 6. They were treated with Eloctate, the first extended half-life therapy to be approved for the treatment of patients of all ages with hemophilia A.
The trial findings, “Final Results of PUPs A-LONG Study: Evaluating Safety and Efficacy of rFVIIIFc in Previously Untreated Patients with Haemophilia A,” were presented at the 2020 Virtual Congress of the International Society on Thrombosis and Haemostasis (ISTH), held recently online. The presentation was given by Christoph Königs, MD, PhD, from the University Hospital Frankfurt, in Germany.
The therapy, marketed as Elocta by Sobi in Europe and the Middle East, is produced in the U.S. by Bioverativ, a Sanofi company. It is the first recombinant clotting factor VIII therapy designed to stay in the body for a considerable period.
The medication is made by linking factor VIII (FVIII), the blood clotting protein missing in people with hemophilia A, to the Fc portion of an immunoglobulin (antibody). The process makes this man-made, or recombinant form of FVIII last longer in circulation compared with standard therapies. That allows for less frequent dosing.
Eloctate was found in previous trials to be a safe and effective therapy for previously treated patients with hemophilia A. However, the effects on individuals who never received any form of treatment for their condition were less clear.
During the ISTH meeting, Königs presented the final findings of an open-label Phase 3 trial called PUPs A-LONG (NCT02234323). It evaluated the safety, tolerability, and efficacy of Eloctate in previously untreated boys younger than age 6 with severe hemophilia A. The trial was funded by Sanofi and Sobi.
The main goal was to determine the percentage of children developing FVIII inhibitors — neutralizing antibodies that render FVIII replacement therapies useless — after being exposed to Eloctate for at least 10 days.
The secondary goals included assessing the percentage of boys developing FVIII inhibitors over the entire duration of the study, as well as the effects of Eloctate on the frequency of bleeds patients experienced within a year. That frequency was assessed by the annualized bleeding rate, or ABR.
From the 103 boys included in the analyses who received at least one dose of Eloctate, 80 (77.7%) were younger than age 1, and 20 (19.4%) had a family history of FVIII inhibitors.
At the study’s start, 81 children began receiving on-demand treatment, while 20 were given prophylactic, or preventive, treatment with Eloctate. Among the boys who started with on-demand treatment, 69 switched to a prophylactic regimen during the study.
A total of 87 participants (84.5%) completed the study. Most of the children (84.5%) were exposed to Eloctate for at least 10 days, with 78.6% being given the medication for at least 50 days.
From those exposed to Eloctate for a minimum of 10 days, approximately a third (31.1%) developed FVIII inhibitors. In half of these children (15.6%), the levels of neutralizing antibodies in the bloodstream were high.
Similar findings were seen in the overall population of children over the entire study, with 27.7% developing FVIII inhibitors and 13.9% having high levels of these inhibitors. Children started developing FVIII inhibitors after being exposed to Eloctate for a median period of nine days.
According to the scientists, the percentage of children developing FVIII inhibitors was within the expected range.
Children receiving on-demand treatment had a median annualized bleeding rate of 2.24, while those receiving prophylactic treatment had a median ABR of 1.49. In both treatment regimens, one infusion of Eloctate was sufficient to resolve most bleeding episodes.
Nearly all children (93%) who participated in PUPs A-LONG experienced at least one treatment-related adverse event, the most common being falls, fever, head injuries, and cold-like symptoms. Serious adverse events associated with the use of Eloctate were seen in 27.2% of the children, and included FVIII inhibition, hemorrhages, and thrombosis.
One boy died from a brain hemorrhage during the screening period of the trial before receiving the first dose of Eloctate.
“Final data from PUPs A-LONG demonstrate that rFVIIIFc [recombinant FVIII] was well tolerated and effective for prevention and treatment of bleeds in a PUP [previously untreated patient] population,” the researchers concluded.
Similar to PUPs A-LONG, this study sought to assess the safety and efficacy of Alprolix (BIIB029) — an extended half-life form of factor IX (FIX) — in previously untreated children and adolescents with hemophilia B. FIX is the blood clotting protein missing in people with severe hemophilia B.
From the 33 participants, only one developed FIX inhibitors after being exposed to Alprolix for 11 days as a prophylactic therapy.
The median ABR was lower in patients receiving on-demand treatment than in boys receiving prophylactic therapy (0.21 vs. 1.24). As in the Eloctate study, a single infusion of Alprolix in PUPs B-LONG was sufficient to resolve most bleeding episodes.
A total of 23 patients (69.7%) experienced serious adverse events, which were treatment-related in two cases — FIX inhibition and hypersensitivity.
“Prophylaxis and treatment of bleeding episodes with rFIXFc [recombinant FIX] was highly effective and generally well tolerated, without unanticipated safety findings,” those investigators wrote.
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