In rare diseases such as PNH, RWD can help provide valuable information about the disease state and its treatment. The International PNH Registry has provided a number of insights into the baseline characteristics and disease burden of patients with PNH, as well as the long-term efficacy of eculizumab in this patient population. In addition, a 2024 retrospective study from the United States described the RW use of anticoagulants in patients with PNH and thrombosis. These types of data help build a picture that is a bit more robust than what we can get from clinical trials alone.

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One of the key pieces of information that people are looking for are RWD related to the use of newer agents for PNH. We have survival and thrombosis data with C5 inhibitors, and we also want to know the survival data with the newer proximal treatment. The timelines of the clinical trials are not long enough to capture survival. The International PNH Registry should, in time, have this information for us.

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Other key pieces of information that we are looking for in terms of future RWD are when and how to use iptacopan and danicopan in patients with PNH. We do not have head-to-head comparisons of these agents. So, how do you decide between monotherapy with pegcetacoplan or iptacopan vs dual therapy with C5 inhibitors and danicopan? We just do not know the optimal approach or patient selection, since these proximal agents were not compared head-to-head. As we gain more experience and as more data emerge with these therapies, we may have a better framework in terms of appropriate patient selection for these different therapies.

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Some other key issues are RW compliance with oral therapy and the consequences of noncompliance. How do we qualify the risks of complications for patients who are not fully compliant with their medications? Are we going to see more breakthrough hemolysis in this setting? We do not have a lot of clinical trial data to help guide the management of these types of situations, making this another data gap that we are hoping to learn more about from RW experiences. An RWD platform called APPRISE-PNH, which is designed to capture RW information on the safety and efficacy of iptacopan, is currently enrolling patients with PNH with an aim to help inform clinical decision making.

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RWD also help us better understand how to treat special populations of patients with PNH, including those who are pregnant. Traditionally, eculizumab has been preferred in this population, but there have been some recent data published supporting the use of ravulizumab. This is an area in which we need people to share their experiences with others to individualize treatment for patients with PNH based on the known risks of different therapies.