We, like many in the hemophilia community, were excited to see extended half-life (EHL) factor VIII and IX products start coming to market over the last few months. These products—and expected future products—promise equivalent or greater prophylactic bleeding control with fewer infusions, and so could greatly enhance patients’ quality of life.
Yet, as we noted in our recent editorial in Haemophilia, we are greatly concerned that patients and providers, seeing the opportunity to reduce their infusion burden, will opt for a dosing strategy that may not benefit patients clinically or financially.
Our concerns stem largely from the dosing schedules recommended in the approved package inserts for the two currently available EHL products: Biogen’s Alprolix™ and Eloctate™. The Alprolix™ factor IX package insert includes two dosing strategies; that for the Eloctate™ factor VIII product recommends one dosing strategy with a range of titration levels.
In changing from a standard to an EHL factor product, providers and patients should aim for either a) better factor levels with the same number of infusions, or b) the same levels with fewer infusions per year. Ideally, either scenario could be achieved with rough cost parity.
Achieving either goal requires knowledge of an individual’s pharmacokinetics on their current standard factor regimen. Clinical trial data and pharmacokinetic models of both factor VIII and IX have shown that there is a broad range in how quickly patients degrade factor.
However, many hemophilia providers do not yet routinely conduct pharmacokinetic assessments on individual patients. Without understanding an individual patient’s factor coverage on standard products, it will be difficult to design an optimal EHL regimen and know how much improvement it provides.
Providers must think critically—balancing convenience, cost and the individual patient’s response to treatment—when considering how to integrate EHL products into their patients’ care.
Additionally, while Biogen asserts a goal of achieving annual cost parity on a market level, how this applies to individual patients is highly variable and cannot be determined without baseline data. The dosing regimens recommended on the EHL package inserts, in particular the Alprolix label, are not equivalent in the factor coverage provided or annual cost. In fact, the convenience of 15 fewer infusions per year would cost a 70 kg adult patient an additional $209,500 each year, while putting them at increased bleeding risk due to lower factor troughs.
While decreasing the frequency with which patients need to infuse may improve the quality of life for some, providers should be cautious about doing this when it results in suboptimal factor levels. If anything, the field is moving in the direction of trying to raise trough levels and help patients safely achieve more active lifestyles.
The ideal prophylactic dosing strategy should emphasize pharmacokinetics, efficacy and cost-effectiveness over convenience. The new EHL products could, when employed properly, make a significant difference in patients’ lives. Indeed, the availability of these and future products creates an opportunity to consider combined EHL/standard factor strategies that could allow providers and patients to achieve better bleeding management. We take inspiration here from other chronic diseases such as diabetes, where patients and providers commonly use both long- and short-acting insulin formulations to achieve target glucose levels.
Providers must think critically—balancing convenience, cost and the individual patient’s response to treatment—when considering how to integrate EHL products into their patients’ care. Patients and families need to understand that fewer infusions may not necessarily equal better management. And they need to have thoughtful discussions with their providers about their hemophilia management goals, how to achieve them and where EHL factor products fit best.
Ellis Neufeld, MD, PhD, is the director of the Boston Hemophilia Center, a pediatric hematologist at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, and the Egan Family Foundation Professor of Transitional Medicine at Harvard Medical School.
Stacy Croteau, MD, MMS, is a pediatric hematologist with the Boston Hemophilia Center and Dana-Farber/Boston Children’s, and an instructor in pediatrics at Harvard Medical School.
This op-ed was originally published on MedPage Today.