Clinical Case: James
Dr Roberts introduces James, a pediatric patient with severe hemophilia A who enjoys playing baseball and whose treatment goals were not being met on his prior nonfactor therapy.
James Transcript
[James] My name is Jonathan Roberts. I'm the Associate Medical and Research Director for the Bleeding and Clotting Disorders Institute and Associate Professor of Pediatrics and Medicine at the University of Illinois College of Medicine in Peoria. I've known James for almost his whole life. He was diagnosed at birth with severe hemophilia A. He also has a younger brother with severe hemophilia A.
He's a very active player on a traveling baseball team. He's 11, he's experienced a lot of different therapies, standard half-life factors, extended half-life factors, nonfactor therapy. But he and his family are concerned because he's experiencing some breakthrough bleeding events while on a nonfactor therapy that was necessitating more factor infusions than he would have liked.
That really kind of brought into the conversation ALTUVIIIO. So things to consider for James was really, he was frustrated with some of the breakthrough bleeds that he had, but he wants to continue playing baseball. Being on the nonfactor therapy in general went well, but then some imaging revealed that he had some early hemophilic elbow arthropathy.
He was on a standard half-life factor for 3 years, an extended half-life factor for 4 years. Currently was on once weekly Factor VIII mimetic for 3 years and was adherent to therapy. Nevertheless, was having some breakthrough bleeds. His right elbow was his target joint and he has no history of inhibitors and no hospitalizations for his hemophilia.
So in considering ALTUVIIIO for him, safety is a big importance for the family, especially with starting a new therapy. The XTEND-Kids was a 52-week multicenter Phase 3 trial for children who were less than 12 years old who had severe hemophilia A. These patients were put on prophylaxis and then have been continued to be followed on the XTEND-ed trial up to 4 years.
The primary endpoints of the XTEND-Kids study was met with 0 neutralizing antibodies detected. After 2 years, the long-term efficacy of ALTUVIIIO in children in XTEND-ed was similar to XTEND-Kids. The mean overall ABR was 0.67 with very few spontaneous bleeds of 0.06, low traumatic bleeds of 0.46, and low joint bleeds of 0.29. The median ABR again was 0. And when you look at the overall patients with 0 bleeds, around 80% of patients had no bleeds whatsoever, with even higher proportion not having spontaneous bleeds, over 97%. If a breakthrough bleed did occur, a majority of bleeding episodes were treated with 1 infusion. So in XTEND-Kids, 95% of bleeding episodes resolved with a single infusion of ALTUVIIIO, 50 units per kilo. And in children in the XTEND-ed study, over 88.5% of bleeds were controlled with 1 injection with over 8% resolving after 2 doses. So children who do have breakthrough bleeding events on ALTUVIIIO are well protected, with most of them only needing 1 infusion.
Getting back to James, he's been doing well on ALTUVIIIO for over a year now. He had been previously frustrated with those breakthrough bleeds that have now resolved with being on ALTUVIIIO prophylaxis. No inhibitor is present and his Factor VIII activity was 42% at day 3, post-infusion, and 12% at day 7. So he continues to excel in his baseball participation, and he looks forward to even participating into the future. The thought of switching to 1 therapy with ALTUVIIIO and getting weekly infusions was really appealing to him and his family.
His family is great. They're very well educated now on hemophilia, you know, living with it in James and his brother, and also family history of maternal grandfather who also had hemophilia.
So the mean treatment duration of patients on the XTEND-ed trial was over 120 weeks from XTEND-Kids and over 68 weeks during the XTEND-ed study.
Similarly, the mean exposure to ALTUVIIIO was over 120 exposure days from XTEND-Kids baseline and 67 exposure days during the XTEND-ed study. In the from XTEND-Kids and XTEND-ed trial, Factor VIII inhibitors did not develop with an incidence of 0 for inhibitor formation in XTEND-ed. The most common adverse events in children, over 12%, was pyrexia. The most common treatment emerging adverse events were cough, arthralgia, and pyrexia. There are no reports of serious allergic reactions, and there is no adverse events leading to discontinuation or death in the study.
[VO] Formation of neutralizing antibodies (inhibitors) to Factor VIII has been reported following administration of ALTUVIIIO.
[VO] INDICATION
ALTUVIIIO® is indicated for use in adults and pediatric patients with hemophilia A (congenital Factor VIII deficiency) for:
- Routine prophylaxis to reduce the frequency of bleeding episodes
- On-demand treatment and control of bleeding episodes
- Perioperative management of bleeding
Limitation of Use
ALTUVIIIO is not indicated for the treatment of von Willebrand disease.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
ALTUVIIIO is contraindicated in patients who have had severe hypersensitivity reactions, including anaphylaxis, to the product or its excipients.
WARNINGS AND PRECAUTIONS
- Allergic-type hypersensitivity reactions, including anaphylaxis, have occurred with ALTUVIIIO. Discontinue use of ALTUVIIIO if hypersensitivity reaction occurs and manage symptoms as appropriate.
- Formation of neutralizing antibodies (inhibitors) to Factor VIII has been reported following administration of ALTUVIIIO. Monitor all patients for the development of Factor VIII inhibitors by appropriate clinical observations and laboratory tests.
- If assessment of plasma Factor VIII activity is needed, it is recommended to use a validated one-stage clotting assay. The ALTUVIIIO Factor VIII activity level is overestimated by the chromogenic assay and a specific ellagic acid-based aPTT reagent in one-stage clotting assay by approximately 2.5-fold. If these assays are used, divide the result by 2.5 to approximate the patient's ALTUVIIIO Factor VIII activity level.
ADVERSE REACTIONS
The most common adverse reactions (>10% of subjects) reported in clinical trials were headache and arthralgia.
Please see full Prescribing Information.
