November 19, 2020
alfapump: Positive interim results from the first 13 patients in the Roll-In Cohort of the North American pivotal POSEIDON study of the alfapump for the treatment of recurrent or refractory ascites due to liver cirrhosis show positive outcomes against all primary endpoints of the study, as well as indications of clinically relevant improvements in quality of life measures.
Professor Florence Wong, University of Toronto, Hepatologist at Toronto General Hospital, Ontario, Canada and Principal Investigator for the POSEIDON study, commented: “I am delighted to see the first, positive, results of these roll-in patients. The dramatic reduction in the need for therapeutic paracentesis and improvement in quality of life is consistent with my long experience with the alfapump. The adverse events were as expected in this population of patients and easily controlled with the standard of care treatments. So if the results are replicated in all study patients, it would be an important improvement in the care for this poorly served patient population.”
POSEIDON is a single-arm, open-label, within-subject crossover study of the alfapump in patients with recurrent or refractory ascites due to liver cirrhosis in the U.S. and Canada. The study includes a “Pivotal Cohort” with up to 50 patients implanted with the alfapump for primary endpoint analysis and an additional “Roll-In Cohort” with up to 30 patients to ensure new centers are familiarised with the alfapump system before they enrol patients in the Pivotal Cohort.
The study is designed to demonstrate in Pivotal Cohort patients 1) a 50% reduction in average monthly frequency of therapeutic paracentesis (TP) post-alfapump implant versus pre-implant and that 2) at least 50% of patients will achieve a 50% reduction in the requirement for TP post-implant versus pre-implant. Paracentesis is the mainstay in chronic clinical management of refractory ascites but it is an invasive procedure, requiring frequent hospitalizations, severely impacting patients’ quality of life and provides only temporary benefit.
In this interim analysis, 13 patients from the Roll-In Cohort (underlying etiology: 61% alcohol, 23% non-alcoholic steatohepatitis (NASH), 8% hepatitis C and 8% mixed etiology) were implanted with the alfapump. Before enrolment, these patients required on average 3.4 TP per month. The mean reduction in the frequency of TP post-implant versus pre-implant was over 90%, with all patients having at least a 50% reduction in the average frequency of TP per month1.
Patient’s quality of life was assessed via established health-survey questionnaires. Results from SF36 (a general health quality survey) indicated clinically relevant improvements in the physical component score and improvement was seen in all SF36 subscales. Ascites Q, a questionnaire developed for patients with ascites also indicated clinically relevant improvement in patient’s quality of life and the improvement was seen in all subdomains of the survey. In both cases, the improvement was seen rapidly (within a month of implantation) and was persistent (6 months after implantation).
Based on these interim data, the safety profile of the alfapump is consistent with previously reported data. The adjudication process by the Clinical Events Committee (CEC) for two alfapump explants in respect of the primary safety outcome is still ongoing.
Ian Crosbie, Chief Executive Officer at Sequana Medical, added: “The substantial reduction in the need for therapeutic paracentesis, good safety profile and clinically relevant improvement in quality of life reported in this study so far is very encouraging. These data further validate the potential of alfapump as a much needed treatment option in this underserved patient population and is an important milestone towards achieving a future marketing application in the U.S. and Canada. The increasing prevalence of NASH-related cirrhosis in this market and the limitations of the current standard of care has been recognized in our FDA Breakthrough Device Designation for alfapump, which will allow us to bring this innovative technology to patients in need as quickly as possible.”
Interim data of the full Roll-In Cohort are expected in H1 2021 and the primary endpoint read-out of the Pivotal Cohort is expected in Q1 2022. The POSEIDON study is intended to support a future marketing application of the alfapump in the U.S. and Canada, with an FDA submission expected in mid-2022.