Clinical Case: Tom
Dr Shapiro introduces Tom, a college-aged patient with severe hemophilia A, and discusses his treatment considerations in the context of his academic and early-career priorities.
Tom Transcript
[Dr Shapiro] I'm Dr Amy Shapiro. I'm a pediatric hematologist. I am Medical Director and CEO of Innovative Hematology and the Indiana Hemophilia and Thrombosis Center in Indianapolis, Indiana. Tom presented due to breakthrough bleeding while on factor mimetic prophylaxis.
He has severe hemophilia A that was diagnosed at birth and has a family history of hemophilia. He is on a factor mimetic prophylaxis and uses an extended half-life Factor VII for his breakthrough bleeding episodes related to playing basketball competitively in college. It is important to consider what Tom's aspirations and interests are.
He goes to college out of state, so he wants to maintain his independence away from home while excelling in his studies and in playing basketball competitively. He wants to go into finance as a career following college and doesn't want his hemophilia to stop him from reaching his goals. He enjoys playing basketball and is highly active.
The question that we need to consider in this case is how can Tom continue being independent and active at the university as he transitions into his adult life? Before discussing Tom's treatment decision, we will take a closer look at his hemophilia journey after his diagnosis. As I said before, he was diagnosed at birth via cord blood testing due to his family history of hemophilia. His brother has severe Factor VIII deficiency, his mother has mild hemophilia, and his sister is also a carrier.
He had been on standard half-life Factor VIII prophylaxis for 11 years, at which time he started extended half-life Factor VIII prophylaxis in 2016 for 3 years. In 2019, he began a Factor VIII mimetic prophylaxis every 4 weeks, with extended half-life Factor VIII used for breakthrough bleeding.
In 2022, he continued his Factor VIII mimetic prophylaxis. However, he changed his regimen to every 2 weeks, and he continued to use extended half-life Factor VIII for breakthrough bleeds. As for his bleed and joint history, he has had multiple muscle bleeds related to trauma, and when playing basketball, and his right ankle arthropathy. He has had surgeries for fracture repairs in 2018 and 2019. Both of these were related to injuries. In 2018, the surgery was for a percutaneous screw fixation of the right distal tibia with a closed fracture of the epiphyseal plate distal tibia. In 2019, he had an open reduction and internal fixation surgery for a right 5th finger fracture. In 2020, he had a left 5th metatarsal fracture. In 2020, he had a left calcaneonavicular coalition resection and left foot interpositional grafting using buttocks fat.
In the Phase 3 XTEND-1 study, a total of 17 patients in the prior prophylaxis group underwent sequential blood sampling for pharmacokinetic assessment up to 336 hours. They underwent this assessment at week 1 with a reassessment at week 26. ALTUVIIIO maintained near normal Factor VIII levels for approximately 4 days, or 86.6 hours, and above 10% for 189 hours. ALTUVIIIO has the longest half-life in adults of 48.2 hours compared to other Factor VIII replacement therapies, 3 to 4-fold longer than Adynovate and Advate.
Steady state Factor VIII trough levels for adults and adolescents at the end of the dosing interval were observed to be approximately 18%.
Factor VIII clearance has been demonstrated to be higher in individuals less than 18 years of age, resulting in lower trough levels. The pharmacokinetic profile was similar after the first dose and after 26 weeks of weekly dosing.
With this history in mind, as well as his aspirations, considerations for switching Tom's treatment were discussed with him. He was experiencing breakthrough bleeding and looking to switch to a treatment that provided confidence while he was at college and after his graduation. After discussions with him, it was decided that Tom would be initiated on ALTUVIIIO in December 2023. So how has he been doing in the last 1.5 years since his initiation on ALTUVIIIO? What's been possible for him? Since starting ALTUVIIIO, he has experienced few, only 3, bleeds related to injury. He continues to participate in basketball competitively, and attends college. He is happy with his independence and is working towards his career goals in finance.
[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.
