Commentary
Video
Author(s):
Etranacogene dezaparvovec offers a long-term, cost-effective solution for hemophilia B by providing sustained factor IX expression but requires careful patient selection and post-infusion liver monitoring.
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, elaborates on the pharmacist's and other treatment provider's roles in treating patients with hemophilia B with etranacogene dezaparvovec (Hemgenix; uniQure, CSL Behring). Pipe explains how etranacogene dezaparvovec offers a transformative approach to hemophilia B treatment, necessitating collaboration between members of the care team.
Among the most important considerations for pharmacists is monitoring patient liver health following etranacogene dezaparvovec, according to Pipe. Alanine aminotransferase (ALT) levels serve as key biomarkers of liver toxicity, so pharmacists must assist in ensuring proper lab work, comparing results with baseline measurements, and guiding decisions regarding immunomodulation. The treatment's cost-effectiveness allows for the opportunity to better optimize patient treatment, Pipe explains.
Pharmacy Times: What considerations should pharmacists and clinicians keep in mind when identifying suitable candidates for treatment with etranacogene dezaparvovec?
1. When selecting patients for etranacogene dezaparvovec, clinicians must assess both eligibility and suitability.
2. Pharmacists and health care teams play a critical role in liver health monitoring, as ALT levels serve as key biomarkers for liver toxicity.
3. While the upfront cost of etranacogene dezaparvovec is high, its long-term cost-effectiveness is significant.
Steven Pipe, MD: I like to distinguish between eligibility—which is your age and your liver health, whether you've had a history of factor IX inhibitors before, whether your hepatitis has been properly treated—and then something that was more along the lines of suitability. I think patient suitability also matters. Beyond the core eligibility criteria, some of the things that we're looking for when we're talking to patients are, what is the commitment to the patient to this therapy and ensuring they get a good outcome? Are they committed to the short- and long-term monitoring requirements? Are they willing to enroll in registry studies so we can collect their data over many decades? Because this is important to inform the community. And how does this therapy align with their own treatment goals? We focus on the lifestyle of the patient. We want to make sure that they have good liver health coming into the trial, but because their liver is going to be transduced by this therapy, we want to make sure that they're adhering to good liver health practices over the longer term. That means complying with things like avoiding any excessive alcohol use and doing other things to make sure you maintain a healthy liver, like maintaining good weight and avoiding some of the possible pathology that might come with metabolic disease because of poor living habits. There are some psychosocial aspects; patients may have anxiety about receiving a treatment like this, and we want to make sure that we've got the right support network around them to educate them, to update them on the most recent data, and answer all of their questions. The last thing is really logistical. We do this therapy infusion, it's a one-time infusion on site, so obviously their ability to come to the clinic for that's important. But it's also the screening efforts and both the liver assessments and the lab tests that are required as a lead-in before you get this therapy, and then the follow-up afterwards.
"I think the pharmacist can be a key participant in this framework."
Pharmacy Times: How can pharmacists monitor and manage potential liver-related adverse effects post-infusion? What role do they and other members of the patient care team play in mitigating these possible risks?
Pipe: I think it starts with identifying the appropriate patient. Because we use particularly the ALT as the biomarker for liver toxicity with this therapy, it's important to have a pre-look at what the range of ALTs are before they receive treatment with etranacogene dezaparvovec. What I like to do is bring the patient in, maybe on a weekly basis for a few weeks, to see what their baseline is and what the sort of range of their ALT fluctuation is. I also do some other things. We know that sometimes transaminases can be derived from other tissues besides the liver, so we counsel them about avoiding excessive exercise leading up to a blood draw. I actually like to, if someone isn't participating in regular exercise, I actually have them do some transaminase levels right after an exercise so that I can see not just the ALT, but also the AST and maybe creatine kinase, which is more derived from a muscle source. That will help me interpret what might happen in the post-infusion stage. We are doing the core liver evaluations like liver ultrasound for structural changes, as well as doing a liver fibrosis analysis. Oftentimes, this is using liver stiffness evaluations; it's a fibroelastometry evaluation of the liver. Once we've deemed that that patient is eligible, now we head into the follow-up period. We need to be educating them on those liver health priorities that I talked about, but then we need a really solid plan for the post-infusion phase: Where are the labs going to be drawn? Who's going to be checking on them? How is that going to be compared with their baseline evaluations? Each of the product inserts has slightly different approaches for the monitoring schedule, as well as the cutoffs for who might need immunomodulation post-infusion. We want to make sure that for the particular therapy they're receiving, the team knows what we're following and what the triggers are, and then how the internal communications are going to happen for deciding when and if we're going to start the course of immodulation according to the product insert. I think the pharmacist can be a key participant in this framework. We have a pharmacist who's now assigned to our multidisciplinary team, and they will have an opportunity to get experience in working with me and the others on the multidisciplinary team, particularly during this post-infusion monitoring phase.
Pharmacy Times: How do you anticipate this therapy will impact the overall cost burden of hemophilia B management for both health care systems and payers?
Pipe: I think what gets all the attention for this therapy in the commercial setting is the upfront costs, because in general, at least within the US, this is a single cost of acquisition, and then you get reimbursed from that from the insurer. The upfront costs are significant, but what we should be paying attention to is also the cost-effectiveness over the long term. Increasingly, we're showing that, particularly for etranacogene dezaparvovec, we're getting long-term, durable, stable activity, which means every year that passes where that patient is no longer needing factor IX prophylaxis is, ultimately, a cost savings to the system. Within just a few years, you've already paid for those upfront costs. If we look at any of the modeling that's been done, cost-effectiveness modeling, including from independent groups for gene therapy, gene therapy is always dominant over the other standard of care treatments available, like both standard half-life and extended half-life factor IX IV infusion. I think this data is just adding to the knowledge and insights that this really does deliver on the cost-effectiveness front. If we look at the fact that two-thirds of the patients are never going to need to treat for a bleed over multiple years, I think this is really impactful.
