Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening disease with symptoms of hemolysis and thrombosis. Current therapies for this complement-mediated disease rely predominantly on inhibition of the C5 complement protein. However, data on treatment responses and quality of life in C5-inhibitor (C5i)-treated PNH patients are scarce. The objective of this study was to determine C5i treatment effects on clinical parameters, PNH symptoms, quality of life, and resource use for PNH patients. This cross-sectional study surveyed 122 individuals in the USA receiving treatment for PNH with C5-targeted monoclonal antibodies, eculizumab (ECU) or ravulizumab (RAV). Despite most patients receiving C5i therapy for ≥ 3 months (ECU 100%, n = 35; RAV 95.4%, n = 83), many patients remained anemic with hemoglobin levels ≤ 12 g/dL in 87.5% (n = 28/32) and 82.9% (n = 68/82) of ECU and RAV recipients, respectively. A majority of patients on ECU (88.6%; n = 31/35) and RAV (74.7%; n = 65/87) reported fatigue symptoms. Among PNH patients receiving C5i therapy for ≥ 12 months, some still reported thrombotic events (ECU, 10.0%, n = 1/10; RAV, 23.5%, n = 4/17) and required transfusions within the past year (ECU, 52.2%, n = 12/23; RAV, 22.6%, n = 7/31). Other patient-reported PNH symptoms included breakthrough hemolysis, shortness of breath, and headaches. Patients reported scores below the average population norms on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scales. Overall, this study found that PNH patients receiving ECU or RAV therapy demonstrated a significant burden of illness, highlighting the need for improved PNH therapies.

Realizing the promise of precision medicine requires patient engagement at the key decision points throughout the cancer journey. Previous research has shown that patients who make the "right" decisions, such as being treated at a high-volume academic medical center, for example, have better outcomes. An online survey was conducted to understand awareness of and barriers to these decision points among patients with multiple myeloma and pancreatic, lung, prostate, and metastatic breast cancers. Survey respondents were identified by 5 participating foundations (multiple myeloma: n = 86, pancreatic: n = 108, lung: n = 56, prostate: n = 50, metastatic breast: n = 86) and recruited by an e-mail or social media invitation. Descriptive analyses were calculated, and the proportion of patients from each of the 5 groups was compared for each response category for each survey item. Consistent gaps in knowledge and actions were identified across all cancers evaluated in terms of finding the right doctors/team at the right center; getting the right diagnostic testing done before beginning treatment; engaging in the right course of treatment, including clinical trials; and in sharing data. Improving awareness of and changing behavior around these 4 decision points will allow patients to receive better care and contribute to the advancement of precision medicine.

INTRODUCTION Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, hematologic disease characterized by chronic complement-mediated hemolysis. Treatment with the C5 inhibitor eculizumab has resulted in a reduction in intravascular hemolysis and improvements in morbidity and mortality. Even with the clinical benefit in PNH, eculizumab entails twice-monthly intravenous infusions in a hospital setting in most countries, adversely impacting patients' work productivity (Mastellos DC, et al.Semin Hematol. 2018;55(3):167-175). Lost productivity associated with eculizumab ranged from $344,000 in Russia to $4.3 million in the United States, without caregivers (Levy AR, et al.Blood. 2019;134(Supplement_1):4803). Furthermore, patients in a real-world study treated with eculizumab for 1 year experienced continued impairment in overall quality-of-life relative-to-normative reference scores for the general adult population (Ueda Y, et al.Int J Hematol. 2018;107(6):656-665). This study aims to understand the clinical, humanistic, and economic outcomes associated with burden of illness in about 150 patients with PNH globally. In these preliminary analyses, productivity loss and quality of life (QoL) in patients with PNH currently being treated with C5 inhibitors (eculizumab and ravulizumab) are assessed in patients in the United States. METHODS This cross-sectional survey administered to adult patients in the United States, ≥18 years of age, with self-reported diagnosis of PNH, was initiated in July 2020 and is ongoing. Patients were recruited through a patient advocacy group. Inclusion criteria to complete the secure online survey include current treatment with either eculizumab or ravulizumab, and agreement to provide informed consent and adverse event reporting. To investigate the impact of PNH on employment and activity, the Work Productivity and Activity Impairment-General Health (WPAI-GH) questionnaire was used. QoL was assessed using Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). For the preliminary WPAI-GH analysis presented here, descriptive statistics are reported for patients who have completed the survey thus far. Analyses examining the impact of PNH on FACIT-Fatigue, EORTC QLQ-C30, and other clinical outcomes assessments among patients on anti-C5 therapy are ongoing. RESULTS A total of 58 adult patients completed the survey as of August 6, 2020. Patients' median age was 52 years (range, 21-88) and 78% of patients were female. Twenty patients (34%) were on eculizumab and 38 (66%) were on ravulizumab. Most patients (93%) had initiated treatment ≥3 months prior to enrollment. In total, 23 (40%) patients reported that they were gainfully employed. Overall, 52% of employed patients reported missing hours of work in the prior 7 days due to their health problems (67% eculizumab and 43% ravulizumab). About 77% of working patients reported that their illness affected their productivity at work (89% eculizumab and 69% ravulizumab) due to the same reason. Employed patients reported an average of 13% (standard deviation, 21%) absenteeism (ie, work time lost due to being absent for illness in the previous week; eculizumab, 22% ± 29%, ravulizumab, 7% ± 12%). Patients reported 26 ± 27% impairment while working over the past 7 days (ie, presenteeism; eculizumab, 39 ± 31%, ravulizumab, 18 ± 22%). Total work productivity impairment was on average 32 ± 31% (eculizumab, 46 ± 35%; ravulizumab, 23 ± 24%). Nearly all patients (n = 54 [93%]) reported at least some impairment in their usual activities regardless of employment (eculizumab, 100%; ravulizumab, 90%). On average, patients reported 38 ± 23% of impaired activity in the previous week (eculizumab, 43 ± 20%; ravulizumab, 36 ± 25%). CONCLUSIONS Preliminary results from this burden of illness survey evaluating humanistic and economic outcomes in patients with PNH demonstrated substantial loss of work-related productivity, greatly diminished ability to work, and limitations in patients' usual activities while being treated with the C5 inhibitors eculizumab and ravulizumab. Disclosures Dingli: Karyopharm Therapeutics:Research Funding;Alexion:Consultancy;Bristol Myers Squibb:Research Funding;Janssen:Consultancy;Rigel:Consultancy;Apellis:Consultancy;Sanofi-Genzyme:Consultancy;Millenium:Consultancy.Matos:Kantar:Current Employment.Lehrhaupt:Kantar:Current Employment.Krishnan:Apellis:Current Employment, Current equity holder in publicly-traded company.Baver:Apellis:Current Employment, Current equity holder in publicly-traded company.Sarda:Apellis:Current Employment, Current equity holder in publicly-traded company.

INTRODUCTION Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, hematologic disease characterized by chronic complement-mediated hemolysis. Treatment with the C5 inhibitor eculizumab has resulted in a reduction in intravascular hemolysis (IVH) and improvements in morbidity and mortality. However, in a single-center cohort of patients with PNH receiving treatment with eculizumab, 72% remained anemic and 36% continued to require transfusions due to ongoing IVH and extravascular hemolysis (McKinley CE, et al.Blood. 2017;130(Suppl 1):3471; Risitano AM, et al.Front Immunol. 2019;10:1157). This study aims to describe the burden of illness in patients with PNH currently being treated with C5 inhibitors (eculizumab and ravulizumab). Overall, the study aims to understand the clinical and hematological outcomes associated with burden of illness in about 150 patients with PNH globally. In these preliminary analyses, the impact of PNH on hematologic and clinical measures is assessed from patients in the United States. METHODS A cross-sectional survey was administered to adult patients ≥18 years of age in the United States with a self-reported diagnosis of PNH, recruited through a patient advocacy group. Inclusion criteria to complete the secure online survey included current treatment with either eculizumab or ravulizumab, informed consent, and agreement to adverse event reporting. This study was initiated in July 2020 and is ongoing. Results presented herein are preliminary. Impact of PNH on hematologic and clinical measures will be assessed using the following variables: diagnosis levels; and any patient history of blood transfusions, thrombotic events, renal impairment, fatigue, and other PNH-associated symptoms as well as dosing frequency and treatment patterns. For these preliminary analyses, descriptive statistics will be reported for patients who have completed the survey. RESULTS As of August 6, 2020, 58 adult patients with a median age of 52 years (range, 21-88) completed the survey, among which 78% were female. Current medications included eculizumab (n = 20 [34.5%]) or ravulizumab (n = 38 [65.5%]), as well as concurrent anticoagulants (n = 9 [15.5%]) and/or anti-thrombotics (n = 2 [3%]). Most patients initiated treatment with eculizumab (n = 20 [100%]) or with ravulizumab (n = 34 [90%]) ≥3 months before. Median (interquartile range) last known hemoglobin level for patients on eculizumab and ravulizumab was 9.3 g/dL (8.0-11.1) and 10.1 g/dL (8.9-11.5), respectively. Overall, 45 (82%) patients reported hemoglobin values <12 g/dL (eculizumab: 90%; ravulizumab: 78%). Forty (69%) patients reported having ≥1 red blood cell transfusion at any point during their disease. Within the previous 12 months, 53% and 26% of eculizumab- and ravulizumab-treated patients, respectively, had ≥1 transfusion, and 12% and 17% were unsure. Among those patients who had ever received ≥1 transfusion, 6% and 13% had >4 transfusions in the previous 12 months for eculizumab and ravulizumab, respectively. Seventeen patients (29%) reported ≥1 thrombotic event at any point during their disease. Seven patients reported thrombotic events over the previous 12 months; six were receiving ravulizumab. The majority (77%) of patients reported fatigue. Fatigue was reported by nearly 95% of eculizumab-treated patients and 68% of ravulizumab-treated patients. CONCLUSIONS Preliminary results from this burden of illness survey demonstrate that a majority of patients with PNH report remaining anemic, despite treatment with C5 inhibitors eculizumab and ravulizumab for a period of ≥3 months. Disclosures Dingli: Sanofi-Genzyme:Consultancy;Karyopharm Therapeutics:Research Funding;Bristol Myers Squibb:Research Funding;Millenium:Consultancy;Alexion:Consultancy;Apellis:Consultancy;Rigel:Consultancy;Janssen:Consultancy.Matos:Kantar:Current Employment.Lehrhaupt:Kantar:Current Employment.Krishnan:Apellis:Current Employment, Current equity holder in publicly-traded company.Sarda:Apellis:Current Employment, Current equity holder in publicly-traded company.Baver:Apellis:Current Employment, Current equity holder in publicly-traded company.

e23052 Background: As precision medicine becomes increasingly important in oncology, patients need to be educated on making decisions at diagnosis to optimize their outcomes. The HBS Kraft Precision Medicine Accelerator is working with national cancer organizations to understand and address gaps in knowledge and action. Informed by prior patient and physician research, the Accelerator developed the Right Track framework, which addresses the unmet educational needs of patients as they navigate their journey. Methods: Participants with newly diagnosed cancer were recruited by the 5 participating foundations from their databases of affiliated patients (MMRF: n = 63, PanCAN: n = 202, LUNGevity: n = 51, PCF: n = 71, MBC Alliance: n = 66). Inclusion criteria included currently living in the US, 25 years or older, diagnosed with a qualifying cancer in the past 12 months (past 18 months for LUNGevity), self-reported as being at least somewhat knowledgeable in their disease, and self-reported as having some input in treatment decisions. The study was conducted by Kantar Health and sponsored by the HBS Kraft Precision Medicine Accelerator. The fielding was conducted in October 2018. Potential respondents were e-mailed an invitation to complete a 20-minute online survey. Potential respondents were also exposed to an invitation via social media from the participating study sponsors. The respondents were asked a series of customized questions that assessed their awareness and behavior on items within each of the four pillars of the Right Track framework. Results: Descriptive analyses were conducted on each of the four pillars (Right Team, Right Tests, Right Treatment, Sharing at Every Step) and it was found that educational gaps exist across all five cancers. Patients require guidance on selecting a knowledgeable team and facility, understanding their specific cancer sub-type and genomic information, participation in clinical trials and the importance of sharing their data. Conclusions: There is a strong need for patient advocacy foundations to work as unbiased, patient-focused organizations, such that they are well-positioned to help close these knowledge gaps.