Bayer's Kogenate approved for paediatric prophylaxis in haemophilia
This article was originally published in Scrip
Bayer HealthCare's Kogenate FS (sucrose formulated recombinant Factor VIII) has received US FDA approval for routine prophylaxis to reduce the frequency of bleeding episodes and the risk of joint damage in children aged 0-16 years with severe haemophilia A with no pre-existing joint damage.
"Administering Kogenate FS to children with haemophilia A on a daily basis before a bleeding event occurs will reduce bleeding into joints and help prevent joint damage, a major cause of disability in haemophiliacs,” said Dr Jesse Goodman, director of the FDA's Center for Biologics Evaluation and Research.
Kogenate FS was first marketed in the US in 1993 for the control and prevention of bleeding episodes and pre-operative management in adults and children aged 0-16 years with haemophilia A.
This approval of the new use is based on clinical data from a US multicentre randomised, open-label Phase III trial involving 65 boys younger than 30 months old with severe haemophilia A, with no pre-existing joint damage, who were randomly assigned to receive either prophylactic or enhanced episodic therapy. The aim was to see if prophylactic Factor VIII infusions, given every other day, were more effective in preventing joint damage than an intensive replacement regimen given at the time of a hemarthrosis. The data were published in the NEJM in August 2007.The study evaluations placed emphasis on the "index joints" the knee, elbow and ankle joints, most prone to bleeding. Joint structural outcomes and functioning were measured at six years of age by radiography, MRI and physical exams.
When the participants reached six years of age, 93% of the prophylactic group and 55% of the episodic-therapy group were considered to have normal index-joint structure, determined by MRI (p=0.002) – the primary endpoint of the study.
The patients in the prophylaxis group had a mean of 3.27 annual haemorrhages, an 81.5% reduction compared to the episodic group – with a mean of 17.69 per person. The prophylaxis group also experienced a mean of 87%fewer joint haemorrhages than those treated episodically.
However, the high cost of this treatment may cause concern; use of recombinant Factor VIII is estimated to account for 90% of haemophilia care. By the age of six, the prophylaxis group were receiving 6,000IU Kogenate per kilogram per year compared with an average of 2,500 IU per kilogram per year in the enhanced episodic group. Priced at $1 per unit of Kogenate, treatment of a child weighing 50kg would be $300,000 per year.
The dosing regimen is also major restriction when implementing the routine prophylactic treatment; difficulties include time required for infusions, unwillingness of the child, limitations in venous access and balancing prophylaxis with other family needs.
"The benefits justify the dedication needed and expense, but long-term advantages and expenses into adulthood remain to be studied," said Dr Craig Kessler of Georgetown University Hospital. "Although the treatment does require family training and compliance, it is recommended to be considered for all patients with no pre-existing joint damage and few prior bleeds in severe haemophilia A thus far."