Sequana Medical has announced additional data on safety, quality of life and survival from POSEIDON, its North American study of alfapump for the treatment of patients with recurrent or refractory ascites due to liver cirrhosis.
Professor Florence Wong, University of Toronto, hepatologist at Toronto General Hospital, Ontario, Canada and principal investigator for the POSEIDON study, commented: “Recurrent or refractory ascites has a negative impact on patients’ lives requiring management with regular paracentesis. The results from the POSEIDON study have shown that the alfapump is very effective at controlling this, virtually eliminating the need for large volume paracentesis and significantly improving patients’ quality of life at six months post-implantation. While patients implanted with the alfapump need to be closely monitored for the development of acute kidney injury or infection, in the POSEIDON study these events readily resolved with the standard of care.”
Ian Crosbie, chief executive officer at Sequana Medical, added: “We are excited about this further POSEIDON data as we believe it continues to support alfapump as a breakthrough for recurrent or refractory liver ascites patients. Together with the positive primary endpoint data reported previously, these results further support the clinical benefits of the alfapump and show a survival rate that compares favourably to literature. With more than 75,000 people in North America suffering from recurrent or refractory liver ascites by 2025, and growing by 6-7% a year due to NASH, modern and effective solutions like alfapump are urgently needed.”
Positive data from the POSEIDON study
Forty patients with recurrent or refractory ascites due to liver cirrhosis have been implanted with the alfapump in the Pivotal Cohort of the POSEIDON study. Of these patients, 48% had an underlying etiology of alcoholic liver disease and 38% suffered from non-alcoholic steatohepatitis (NASH), reflecting the growing prevalence and importance of NASH as a key driver of liver cirrhosis. Before enrolment, these patients required on average 3.2 therapeutic paracentesis (TP) per month and had an average MELD score of 15.2, indicating the severely decompensated state of these patients.
As previously reported, Pivotal Cohort patients met all pre-specified primary effectiveness endpoints with statistical significance at six months post-implantation, including:
- 100% median per-patient reduction in TP post- vs pre-implant (p<0.001), vs hypothesis of at least a 50% reduction, and
- 77% of patients with at least 50% reduction in number of TP post- vs pre-implant (p<0.001), vs hypothesis of at least 50% of patients.
Primary safety endpoint data, including the rate of alfapump-related open-surgical re-interventions, explants or deaths adjudicated by the Clinical Events Committee (CEC), were in line with expectations with six primary safety events. Of the six primary safety events, three were explants due to wound or skin erosion, and three were explants due to patient-reported discomfort (all patient-reported discomfort events were adjudicated by the CEC as moderate severity).
Key secondary endpoints within six months, also adjudicated by the CEC, include the number of Major Adverse Events (MAE), serious infections and acute kidney injuries (AKI). MAEs were pre-defined in the protocol together with the principal investigators and Food and Drug Administration (FDA) as one of the following events: AKI > stage 2, hepatorenal syndrome, hepatic encephalopathy > grade 2, spontaneous bacterial peritonitis and reccurent or refractory infection related to paracentesis or the alfapump system, procedure or therapy. Despite disease progression, there was a similar number of MAEs post-implant vs pre-implant (N=5 vs N=5) as well as a comparable number of serious infections post-implant vs pre-implant (N=3 vs N=2) of which only one post-implant serious infection was adjudicated to be device-related.
Renal function is often impaired in patients with advanced cirrhosis and patients with evidence of renal failure were excluded from the study. Therefore post-implant vs pre-implant AKI rates are not comparable because any patient with a non-transient AKI in the pre-implant period was not implanted with the alfapump and excluded from the Pivotal Cohort. In the six months post-implantation, most AKIs were stage 1 (N=16) which are of limited clinical relevance. AKI stage 2 (N=4) and stage 3 (N=2) post-implantation were resolved in three instances and unresolved at the time of death from unrelated cause in three other instances. Importantly, creatine and eGFR levels were stable over long-term follow-up indicating that these AKI events had no impact on their renal function.
Patient’s quality of life was assessed via established health-survey questionnaires. Despite disease progression in these patients, both the physical component score of SF36 (a general health quality of life measure) and the Ascites Q score (a quality of life measure specific for patients with ascites) indicated clinically meaningful and statistically significant improvements six months post-implant vs pre-implant (N= 26, p<0.001).
Although the POSEIDON study was not powered for survival outcome, a positive trend in survival was observed in patients implanted with the alfapump, with a Kaplan-Meier estimate indicating a 70% survival probability at one year post-implantation. This compares favourably with the published literature reporting a survival rate for refractory ascites patients of only 50% at 12 months.
Data from the POSEIDON study will be submitted for publication in a peer-reviewed journal in 2023.