Sequana Medical announces additional alfapump data supporting strong and durable clinical profile; PMA on track for year-end submission

• One-year alfapump data from POSEIDON shows safety and strong efficacy profile is maintained at 12 months

• Patient preference study indicates that US patients have a strong preference for the alfapump vs large volume paracentesisi

• Matched interim analysis of patients from NACSELDii registry and POSEIDON pivotal cohort indicates that alfapump safety profile is comparable to standard of care

• Positive pre-PMA (iii) meeting held with FDA to align on clinical data and benefit-risk analysis for the submission package

• On track for PMA submission by year end

Gijs Klarenbeek, Senior Medical Advisor of Sequana Medical, commented: “These data are very positive and demonstrate that the alfapump continues to transform the lives of patients with recurrent or refractory ascites at one year post-implantation, maintaining the virtual elimination of needle paracentesis and clinically meaningful improvement in quality of life. The comparison of POSEIDON patients to a matched cohort of subjects in the NACSELD registry is reassuring as it reaffirms alfapump’s safety profile.”

Ian Crosbie, Chief Executive Officer at Sequana Medical, added: “We are delighted with these additional insights into alfapump’s long term benefit as well as the encouraging results from our patient preference study which indicates a strong preference amongst US patients for the alfapump. We are greatly encouraged by our recent pre-PMA meeting with the FDA, where we discussed the reported clinical data from our alfapump studies and benefit-risk analysis for the submission package. We look forward to submitting our PMA application by year end and continuing our preparations for launching the alfapump in the US and Canada."

One-year follow-up data from POSEIDON study

As seen in months 0-6 post implant, patients maintained the 100% median reduction in therapeutic paracentesis in the 7-12 month post-implant period vs the three month pre-implant period (n = 19). These data show that the alfapump has a sustained effect on controlling ascites, virtually eliminating the need for therapeutic paracentesis.

During the 7-12 month post-implant period, two patients had the alfapump explanted, one due to a urinary tract infection and one due to wound dehiscence and the number of Major Adverse Events (MAEsiv) and serious infections were in line with expectations. Importantly, creatine and eGFR (v) levels of alfapump-treated patients over 12-month follow-up indicated a stable renal function. Overall, these safety data indicate that the alfapump has a robust safety profile over long-term follow-up.

Quality of life, assessed through 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), maintained a clinically meaningful improvement at 12 months post-implant vs three months pre-implant, despite disease progression.

The overall trend in survival (vi) in patients implanted with the alfapump remained positive over a longer term, with a Kaplan-Meier estimate indicating over 70% survival probability at 12 and 18 months post-implant. This compares favourably with the published literature reporting a predicted survival probability for refractory ascites patients with a similar MELD (vii) score and receiving paracentesis of approximately 17% at 12 months and 5% at 18 months (viii).

Data from the POSEIDON study will be submitted for publication in a peer-reviewed journal. The Company will update the market as soon as it is published.

Outcome Patient Preference study

The patient preference study was conducted by RTI Health Solutions, thought leaders in the field. The rigorous study design was pre-discussed with the FDA and utilizes a discrete-choice experiment (DCE (ix)) methodology to elicit preferences of US patients with a physician-confirmed diagnosis of recurrent or refractory ascites due to liver cirrhosis for attributes of an implantable pump as a novel interventional treatment for ascites. Patients were surveyed for the risk of treatment-related adverse events they would be willing to accept (risk tolerance) to achieve specific improvements in treatment efficacy (desired benefits). In total, 125 US patients with a comparable patient profile as the Pivotal Cohort in the POSEIDON study, completed the survey.

Top-line results presented in the table below indicate that, on average, patients are willing to accept levels of risks greater than those observed in the POSEIDON study in exchange for improvements in treatment efficacy less than or equal to those observed in the POSEIDON study.

Reduction in paracentesis frequency and additional ascites good health days are important attributes for a novel interventional treatment for ascites. On average, patients responded with a 65% likelihood of selecting a treatment profile like the alfapump vs regular paracentesis procedures and no implanted pump.

These data support the premise that alfapump is a desirable treatment option for the majority of patients.

Matched interim analysis of NACSELD registry and POSEIDON pivotal cohort

The North American Consortium for the Study of End Stage Liver Disease (NACSELD) is a consortium of tertiary-care hepatology centers in North America formed to study patients with cirrhosis. NASCELD-III is an IRB (x) approved registry of outpatients with cirrhosis which was initiated in 2019 at ten centers in North America.

A matched cohort analysis was conducted by an independent group comparing outcomes of decompensated cirrhosis patients from the NACSELD-III registry to those from the POSEIDON study. Forty decompensated ascites patients from NACSELD-III were matched to the forty patients from the Pivotal Cohort in the POSEIDON study, using baseline Ascites-Q score (reflecting burden of disease before alfapump implantation) and sex. Patients were also comparable for age and baseline MELD score after matching.

Results for all cause hospitalization and death within six months were similar between the NACSELD-III registry matched patients and the POSEIDON pivotal cohort.

This analysis indicates that the safety profile of the alfapump is in line with expectations and comparable to standard paracentesis procedures.

Data from the matched cohort analysis together with the positive data from the POSEIDON study indicate that patients implanted with the alfapump benefit from significantly reduced number of paracentesis procedures and an improved quality of life without an increased risk of death or hospitalization compared to standard of care.

(i) Large volume paracentesis is paracentesis of more than 5 liters (and part of standard of care)
(ii) NACSELD: North American Consortium for the Study of End stage Liver Disease
(iii) PMA: Pre-Market Approval
(iv) MAEs were pre-defined in the protocol together with the principal investigators and 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.
(v) eGFR: estimated Glomerular Filtration Rate, a measure of kidney function
(vi) POSEIDON study not powered for survival
(vii) MELD: Model for End-Stage Liver Disease scoring system based on laboratory parameters, and is used to predict three-month survival rate and consider patients for liver transplantation
(viii) Salerno et al., Gastroenterology 2007; 133:825-834; figure 2: estimated probability of death according to treatment allocation (TIPS or paracentesis) in hypothetical patients with different MELD scores
(ix) The DCE approach allows an analysis of individual stated preferences in response to hypothetical choices and enables the quantification of the relative importance of each attribute/level during the decision-making process.
(x) IRB: Institutional Review Board
(xi) Deaths and serious adverse events (SAE) requiring hospitalization are presented hierarchically such that if a subject died and experienced an SAE requiring hospitalization, they are counted under “Death”
(xii) POSEIDON data are derived from adverse event data during six months post-implant