Study Highlights Experiences with Familial Chylomicronemia Syndrome After Olezarsen Use

Most individuals treated with olezarsen with familial chylomicronemia syndrome (FCS) will see meaningful improvements in disease symptoms, recent findings suggest, supporting the efficacy of olezarsen therapy.1

These data resulted from a sub-study of the open-label extension (OLE) of the randomized, placebo-controlled phase 3 ‘Balance’ analysis.2 This OLE sub-study was authored by such investigators as Asia Sikora Kessler, PhD, of Ionis Pharmaceuticals in Carlsbad, California.

Kessler et al noted that, in the context of the Balance study and its associated OLE study, they would carry out a sub-study via qualitative interviews to further examine the FCS patient experiences prior to and during treatment with olezarsen.

“Specifically, the objectives of the sub-study were to capture patients’ experiences prior to starting the Balance study, to explore the effect of study treatment on the symptoms and impacts related to FCS during Balance or the OLE study, and to characterize the meaningfulness of any changes experienced during treatment,” Kessler and coauthors wrote.1

Design and Findings

The trial investigators highlighted the rare, hereditary nature of FCS, a condition characterized by severely elevated plasma triglyceride levels and a substantially heightened risk of acute pancreatitis. The associated symptoms of FCS can severely impact the day-to-day functioning and overall quality of life of patients with the condition.

Kessler and colleagues' OLE study (NCT05130450) followed the randomized, placebo-controlled phase 3 Balance trial (NCT04568434). During the analysis highlighted here, these patients continued treatment with olezarsen and took part in one-hour qualitative interviews. Their interviews also underwent thematic analysis.

Subject recruitment took place across 8 clinical sites in 4 countries. The interviews were carried out with a subset of OLE participants from Canada, the US, Italy, and Spain. To ensure that participants previously assigned to placebo in the Balance study had sufficient time to experience the treatment’s effects, these discussions took place following the 13-week visit of the OLE. Ethics approvals were obtained from relevant local and national review boards.

There were 18 from the OLE study who completed their interviews; 55.6% of these individuals were reported as female, and the average age was noted as 43.5 years. Seventeen of these individuals had reported having pancreatitis in the past, with 14 noting episodes within the decade prior to joining the Balance study. Among these 14, 13 had needed hospitalization.

Every participant reported experiencing symptoms attributed to FCS before entering the clinical trial.1 Among the most commonly reported symptoms, abdominal pain among 94.4%, physical fatigue among 66.7%, diarrhea, among 55.6%, vomiting among 50.0%, nausea among 33.3%, and cognitive issues among 27.8% were highlighted by Kessler and coauthors. FCS conditions also impacted participants’ lives in an array of different ways, including strict dietary limitations among 100%, emotional and mood-related effects in 94.4%, restrictions on social activity in 77.8%, and hospitalizations in 77.8%.

After the trial subjects continued using olezarsen, the investigative team noted that 83.3% of the 18 individuals reported having clinical and lifestyle improvements. Relief from FCS symptoms included reductions in abdominal pain among 82.4%, fatigue among 58.3%, diarrhea among 60.0%, vomiting among 87.5%, nausea among 60.0%, and cognitive abilities among 60.0%. Those taking part in the sub-study also noted improvements in broader impacts such as personal relationships (85.7%), their frequency of hospitalization (78.6%), financial issues (75.0%), and mood/emotional wellbeing (70.6%).

Overall, Kessler and colleagues noted that 83.3% of the trial participants described these changes as being meaningful and expressed satisfaction with olezarsen as a treatment for their condition.

“Results from this Balance interview sub-study support the effectiveness of olezarsen from the patient perspective,” the investigative team concluded.1

References

1. Brown TM, Bratlee‐Whitaker E, Kessler AS, et al. Journal of clinical lipidology, 2024, 18(4), e568‐e569 | added to CENTRAL: 31 August 2024 | 2024 Issue 8. https://doi.org/10.1016/j.jacl.2024.04.105.

2. Stroes ESG, Alexander VJ, Tsimikas S, et al. Balance Investigators. Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome. N Engl J Med. 2024 May 16;390(19):1781-1792. doi: 10.1056/NEJMoa2400201. Epub 2024 Apr 7. PMID: 38587247.