The European Medicines Agency (EMA) has released a new reflection paper on the risks of adverse immune system reactions in hemophilia patients treated with Factor VIII products and how these factors might be mitigated in the future.

EMA explains in its 31 July reflection paper that up to 30% of patients with severe hemophilia A experience a buildup of neutralizing antibodies against the treatment, which can cause bleeding. Current therapies tend to focus on treating the symptoms of this buildup rather than the underlying cause, EMA notes, and bleeding control therapies are widespread among specialized hemophilia centers.

While these treatments can be effective, EU regulators implied they would rather obtain a deeper understanding about the underlying causes of the adverse events to spur the development of alternate treatment options for those not well-served by the treatments. EMA said the success of FVIII treatments is largely dependent upon a number of factors, including genetics, treatment history, infections, time to treatment, dosing and the duration of treatment.

"All these data support the assumption that inhibitor eradication is a therapeutic approach that has to be tailored for the individual patient," EMA writes.

"Longstanding clinical experience shows that immune tolerance induction significantly contributes to therapeutic success," continues EMA. "However, commonly agreed eligibility criteria for concerned patients, treatment regimens regarding dosage and duration as well as success criteria for reproducible documentation of efficacy have not been developed so far."

The agency goes on to say that, "Clear cut recommendations on the clinical trial concept for an individual product in order to achieve an indication claim for immune tolerance induction cannot be given at present," and clinical research to support the concepts of such a trial need to be supported.

In the meantime, EMA notes sponsors might include information about the personalized management of inhibitor patients in Section 5.1 of the summary of product characteristics (SmPC) as long as it is supported by clinical data. Regulatory acceptance of these statements will be determined on a "case by case" basis.

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EMA - Reflection paper on immune tolerance induction in haemophilia-A patients with inhibitors