Commentary
Video
Pharmacists are integral to setting patient expectations, monitoring liver health, and ensuring adherence to long-term follow-up for optimal outcomes with etranacogene dezaparvovec.
In an interview with Pharmacy Times®, Steven Pipe, MD, a Laurence A. Boxer research professor of pediatrics and professor of pathology at the University of Michigan in Ann Arbor, explains how pharmacists play a crucial role in counseling patients on etranacogene dezaparvovec (Hemgenix; uniQure, CSL Behring) for hemophilia B by setting realistic expectations about the extensive pre-screening and post-infusion monitoring required for treatment success.
Pipe notes that pharmacists help assess liver enzyme fluctuations, ensuring that factors such as exercise, alcohol intake, or new medications are accounted for when interpreting test results. Given the variability in patient responses to the therapy, pharmacists also assist in managing trauma and surgical considerations, ensuring appropriate prophylaxis when necessary. With 4 years of phase 3 trial data reinforcing the therapy’s safety and efficacy, ongoing research aims to expand eligibility criteria for etranacogene dezaparvovec, making pharmacists key contributors in guiding patients through this evolving treatment landscape.
Pharmacy Times: What are key points pharmacists should focus on when counseling patients on etranacogene dezaparvovec, particularly in terms of expectations, monitoring, and long-term follow-up?
1. Patients must undergo extensive pre-screening and weekly post-infusion evaluations for several months to monitor liver health.
2. Pharmacists help identify and address factors affecting liver enzyme levels, including exercise, alcohol, and medication interactions.
3. Individual factor IX responses vary, requiring tailored management, and ongoing trials are exploring eligibility expansion.
Steven Pipe, MD: I think they can be part of the multidisciplinary team, really setting realistic expectations about this therapy. There are significant post-infusion monitoring requirements. This is a single time frame infusion for the treatment, but the commitment, both in the screening up front and then in the post-infusion, is a significant burden, at least for the first several months. It's at least weekly evaluations. Now, these don't have to be clinic visits with physical exams, necessarily, but it does mean coming to a place where you can get accurate transaminase levels in a quick turnaround and have those reviewed and adjudicated, and when appropriate, make a decision about the need for immunomodulation. That's where the pharmacist can be part of that team, setting the expectation with the patient about, “Okay, this is what you are committed to if you receive this therapy if you want to get a good outcome,” at least as good as what's been reported in these long-term data. We also set the expectation of what the likelihood of actually having transaminitis that would actually trigger the corticosteroid therapy is. That ranges across the trials. For etranacogene, it was relatively low; there were only 9 of the 54 patients who had a transaminase elevation that triggered the immunomodulation, and I think there were only 10 individuals overall who had any sort of significant increase in their liver enzymes that was deemed to be related to the product. There were some elevations that we could track back to determine that it was perhaps exercise-induced, etc. So, again, when we're evaluating these transaminase levels, at some point there's going to have to be an evaluation, “Okay, this looks like an elevation above the patient's baseline.” Call to the patient: “Okay, what's going on? Did you do some exercise yesterday that you didn't recognize might have impacted your therapy? Did you consume some alcohol that could be responsible for that elevation? Did somebody start a new drug that might have some liver toxicity?” We've actually seen that, not in this trial, but in other trials, where a patient's concomitant drug use has actually influenced the transaminase levels and maybe confused the picture. That's again where pharmacists can have a key role in identifying that this patient has been started on this new medication; is this potentially something that could be interacting here and contributing to these transaminase elevations we're seeing? The third piece, as far as setting realistic expectations, is the wide individual variability in both the degree and the durability of response. We're seeing pretty good stability for the group on the whole; at an individual level, there could be some variability. I mentioned that 98% of the individuals who received etranacogene dezaparvovec have levels at least 5% or higher, and about a third are in the non-hemophilic range. But across that range now, we have variable levels of factor IX expression, and that has implications for, well, how are we going to manage that patient if they do have a traumatic injury? What if the patient needs an elective surgery, for some perspective? We need to recognize that some patients are going to have different levels, and how they have behaved with responses to trauma on those levels is going to influence whether or not they need treatment, and then some decisions about who needs additional prophylaxis may be for a surgical intervention. All of these are part of the discussion with the patient, where I think the pharmacist can be part of that core multidisciplinary team in helping coach the patient around these issues.
Pharmacy Times: Is there anything else that you wanted to add?
Pipe: withI think the fact that we now have 4 years of long-term data from a phase 3 trial for something that is so potentially life-transforming as this is really exciting. It's continuing to reinforce the safety and the efficacy of this intervention and also the broad eligibility that comes with this particular therapy, etranacogene dezaparvovec, the fact that we're not really seeing any difference between the NAV positive and the NAV negative patients, at least up to certain thresholds of neutralizing antibody positivity. There is actually an ongoing trial that's going to answer the question of if there are patients above a titer of 678, which is the highest level that we have long-term efficacy data on, and that trial is ongoing now, and it is enrolling patients globally. I think that's going to fill in the gaps between a non-responder that we had at the very highest level and then everybody in between. I think in a few years, we're going to have really solid data to tell us who can actually receive this therapy and expect to have a good outcome.
