Real-world (RW) study data provide important validation of clinical trial results, particularly for rare diseases such as paroxysmal nocturnal hemoglobinuria (PNH). Emerging RW data on treatment outcomes in PNH, including health-related quality of life (HRQOL), were presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition.

Following these presentations, featured expert Ronald S. Go, MD, was interviewed by Conference Reporter Medical Director Lauren Weinand, MD. Dr Go’s clinical perspectives on these findings are presented here.

For rare diseases such as PNH, having validation from RW experience with regard to the efficacy and safety of treatments, as well as QOL improvements, is particularly important because the numbers of patients participating in phase 3 clinical trials are typically small. Thus, having validation from RW studies enrolling more patients of different races and ethnicities from different countries is critical. In addition, RW studies can also provide longer-term outcomes data for drugs that are approved by the US Food and Drug Administration (FDA) or are under investigation.

Laboratory values such as hemoglobin levels can only measure one aspect of the clinical side of patients with PNH. Improvements in laboratory values usually equate to the patient feeling better, but the relationship is not one-to-one. For example, a person with a hemoglobin level of 11 or 12 g/dL may subjectively feel a lot better than someone else with the same disease who has a similar hemoglobin level. So, again, laboratory values capture only one aspect of the condition, and it is therefore essential to measure HRQOL outcomes in addition to laboratory parameters. After all, QOL affects patients’ daily functions, such as whether they are able to go to work and care for their families—and even whether they are able to go to their clinics for doctor visits.

Several abstracts presented at ASH 2024 reported on data from RW studies that provide important validation of the efficacy and safety of therapies for the treatment of PNH. For example, a multinational, cross-sectional survey by Jens Panse, MD, and colleagues of hematologists who prescribed pegcetacoplan for patients with PNH found that treatment was associated with increases in mean hemoglobin levels, decreases in lactate dehydrogenase levels, and improvements in fatigue (abstract 5085). Benefits were seen both in patients who had previously received C5 inhibitors and in those who were treatment naive. These outcomes were generally consistent with those reported in clinical trials. Notably, adherence rates were generally good, with approximately 91% of complement-naive patients and 87% of complement-experienced patients reporting complete adherence to treatment. These data are important because they show improvements not only in laboratory parameters but also in how patients were feeling.

Another abstract presented at the recent ASH meeting reported the French National Reference Center’s RW data on pegcetacoplan therapy (abstract 1321). The analysis included 39 patients who had breakthrough hemolysis on prior anti-C5 therapy (ie, eculizumab or ravulizumab) and were treated with pegcetacoplan. More than half of patients (63%) experienced an improvement in their breakthrough hemolysis and were able to obtain a hemoglobin level of higher than 12 g/dL after 12 months of pegcetacoplan exposure. This highlights that a substantial proportion of patients—although not all—respond to this proximal inhibitor when anti-C5 therapy does not work completely.

Abstract 5074 by Elizabeth A. Griffiths, MD, et al reported findings from the ADVANTAGE study, which analyzed data from a US health insurance claims database on adherence, persistence, and health care resource utilization in patients with PNH who received anticomplement therapy (ie, eculizumab, ravulizumab, or pegcetacoplan). The authors measured adherence indirectly by looking at insurance claims to determine the proportion of days covered and the treatment duration rather than looking at patient charts or speaking with patients or physicians. It also must be noted that this was a company-sponsored trial. The authors did find higher adherence and persistence rates for ravulizumab, the longest-acting agent, as well as significantly fewer PNH-related hospitalizations.

Finally, an abstract presented at ASH 2024 looked at long-term HRQOL in patients receiving iptacopan as part of the APPLY-PNH and APPOINT-PNH trials (abstract 4079). The study found that patients who switched from anti-C5 therapy or were treatment naive achieved both HRQOL improvements and investigator-assessed improvements in PNH signs and symptoms. This suggests that monotherapy treatment with iptacopan is effective at improving not only laboratory parameters but also QOL parameters that are important to patients.