Federico Grossi
Management
Thank you, Cedric. I'd like to begin by reminding everyone why we believe that pegcetacoplan has the potential to elevate the standard of care for people living with PNH. PNH is characterized by the destruction of pulp season carrying red blood cells through both extravascular and intravascular hemolysis caused by uncontrolled complement activation. Current treatments inherent the complement cascade downstream at C5, controlling intravascular but not extravascular hemolysis. As a result, while C5 inhibitors offer improvement patient survival, they do not add as many debilitating symptoms from which people living with PNH continue to suffer. Early pegcetacoplan target complement centrally at C3, controlling both intra and extravascular hemolysis. As a result, pegcetacoplan met the primary endpoint in the Phase III PEGASUS study and became the first and only investigational therapy to demonstrate superiority compared to Soliris or eculizumab, with an improvement in adjusted means of 3.8 grams per deciliter of hemoglobin at week 60, as well as sustained improvements in other key clinical measures. The safety profile of pegcetacoplan was comparable to Soliris . Based on these results, we received priority review from the FDA for pegcetacoplan in PNH with a PDUFA date of May 14. Additionally, in December, we announced top line data at week 48 from the PEGASUS study. These long-term results show that pegcetacoplan has the potential to help PNH patients gain and maintain more complete control of the disease. At week 48, hemoglobin increases were sustained with pegcetacoplan-treated patients with a mean improvement from baseline equal to the increase in existing in pegcetacoplan-treated patients. Importantly, as you can see in the graph, Soliris-treated patients who switched to pegcetacoplan during the open-label period also experienced sustained improvement in hemoglobin and other key clinical measures, similar to patients treated with pegcetacoplan monotherapy during the randomized controlled period. Sustained improvements in transfusion avoidance, reticulocyte count, lactate dehydrogenase or LDH levels and functional assessment of chronic illness therapy or FACIT-fatigue scores were also observed in patients treated with pegcetacoplan. At week 48, the safety profile of pegcetacoplan was consistent with previously reported data and non-new safety signals were identified. Also, in December, at ASH, we presented a matching adjusted indirect comparison, or MAIC, analysis across the pivotal studies called pegcetacoplan and Ultomiris or ravulizumab, a longer C5 inhibitor. In the absence of clinical head-to-head study, MAIC is a valid and accepted method for comparative effectiveness research used by health technology assessment bodies across the world. The MAIC showed that pegcetacoplan, 76% more patients achieved hemoglobin stabilization compared to patients on Ultomiris. Also, 64 more patients in pegcetacoplan achieved LDH normalization. This is remarkable because LDH is a biomarker of intravascular hemolysis, the top hemolysis that C5 inhibitor like Ultomiris control well.