Patient Experience with Familial Chylomicronemia Syndrome before and after Olezarsen Treatment: Qualitative Interviews with Clinical Trial Participants.

Ionis Pharmaceuticals, Inc. Familial chylomicronemia syndrome (FCS) is a rare genetic disorder that markedly increases plasma triglycerides (TG), causing pancreatitis, abdominal pain, and other symptoms that profoundly impact patients' quality of life. In a randomized, placebo-controlled phase 3 study (Balance; NCT04568434), olezarsen significantly reduced TGs among adults with FCS. To further explore the FCS patient experience during olezarsen treatment, including perceptions of meaningful changes in FCS symptoms and impacts. Patients with FCS (US, Canada, Spain, Italy) continuing olezarsen treatment in an open-label extension (OLE) of the Balance study participated in 1-hour semistructured qualitative interviews via telephone. Thematic analysis was conducted. Eighteen of 60 OLE participants completed interviews (10 female; 55.6%); mean age at interview was 43.5 (range, 23-73) years. (See Table 1 for participant characteristics.) When interviewed, participants randomized to active drug in Balance had received olezarsen for 67-113 weeks, whereas participants randomized to placebo had received olezarsen for 16-47 weeks. Seventeen of 18 participants reported a history of pancreatitis, including 14 with pancreatitis events in the 10 years prior to enrollment in the Balance study (13/14 requiring hospitalization). Moreover, all participants reported experiencing at least 1 FCS-related symptom prior to enrollment, such as abdominal pain (n=17; 94.4%), physical fatigue (n=12; 66.7%), diarrhea (n=10; 55.6%), vomiting (n=9; 50.0%), nausea (n=6, 33.3%), and difficulty thinking (n=5, 27.8%). Fifteen participants reported being symptomatic in the absence of pancreatitis, most commonly experiencing abdominal pain (n=12). All participants reported FCS-related impacts, including dietary restrictions (n=18; 100%), mood/emotions (n=17; 94.4%), hospitalizations (n=14; 77.8%), and social activities (n=14; 77.8). Participant feedback on treatment-related improvements was based on their experiences and belief of starting olezarsen, either within Balance or OLE. Fifteen of 18 participants (83.3%) reported improvements, including reductions in FCS-related symptoms (abdominal pain [n=14/17; 82.4%], physical fatigue [n=7/12; 58.3%], diarrhea [n=6/10; 60.0%], vomiting [n=7/8; 87.5%], nausea [n=3/5; 60.0%], difficulty thinking [n=3/5; 60.0%]) and impacts (relationships [n=6/7; 85.7.0%], hospital admittances [n=11/14; 78.6%], finances [n=3/4; 75.0%], mood/emotions [n=12/17; 70.6%]). All 14 participants with pancreatitis events in the past 10 years reported pancreatitis-related improvements, including 11 (78.6%) with no pancreatitis events and 3 (21.4%) with less frequent and/or less severe events since they believed they started olezarsen treatment. Overall, most participants (15/18; 83.3%) reported meaningful improvements and indicated they were satisfied with olezarsen treatment. Results of this qualitative study both underscore the significant burden of FCS and support the efficacy of olezarsen from the patient perspective. [ABSTRACT FROM AUTHOR]