Sequana Medical NV (Euronext Brussels: SEQUA), a commercial stage medical device company focused on the development of innovative treatment solutions for the management of liver disease, heart failure, malignant ascites and other fluid imbalance disorders, today announces the presentation of the positive results from the first-in-human single dose DSR proof-of-concept study for volume overload due to heart failure. The investigator-initiated study was conducted by Dr. Jeffrey Testani of Yale University. The study demonstrated that single dose DSR therapy in humans was safe and well-tolerated and resulted in a clinically relevant removal of sodium with consistent results between treated patients.

A key problem in treating patients with volume overload is that the removal of fluid without the removal of the associated sodium only results in a temporary benefit. Sequana Medical’s innovative DSR therapy removes the sodium and then the body eliminates the associated fluid to restore the sodium concentration, resulting in sustained fluid removal. Data from this study demonstrate that DSR can result in the removal of large quantities of sodium and fluid in a safe and tolerable manner. This underscores the potential of Sequana Medical’s alfapump DSR to deliver a new and convenient treatment option for patients with volume overload due to heart failure.

The results have been presented during the late-breaking abstract session at the Heart Failure 2019 congress in Athens, Greece, today at 08:30 CEST (09:30 local time in Athens), by Dr. Jeffrey Testani, Associate Professor and Director of Heart Failure Research at Yale University. The abstract and presentation are available on the Sequana Medical website.

Dr. Jeffrey Testani, Associate Professor at Yale University, commented:“There is a clear unmet need in the management of volume overload and congestion in heart failure patients. Loop diuretics are our current mainstay of therapy but the adverse effects of these drugs are well described and development of diuretic resistance leading to progressive volume retention is common. The results of this study, together with the previously reported animal data indicate that DSR is a promising candidate therapy in heart failure. We are optimistic that future research will demonstrate that combining the novel DSR treatment approach with Sequana Medical’s established alfapump platform will deliver a convenient and effective non-diuretic treatment option in heart failure.”

Ian Crosbie, CEO of Sequana Medical, added: “With volume overload accounting for 90% of the one million hospitalisations for heart failure each year, it is clear that better treatment options are needed to address the $13 billion in U.S. hospital costs for heart failure. These positive first-in-human results reinforce our beliefs in the potential of our proprietary DSR therapy. We are excited to drive forward the clinical development of alfapump DSR, combining the accumulated positive results of DSR with our validated alfapump platform. We can leverage our extensive technical and clinical experience from the cirrhotic ascites and malignant ascites markets to de-risk our alfapump DSR development program in heart failure. We plan to commence the first clinical study of alfapump DSR in the second half of 2019 as the next step in this breakthrough program.”

First-in-human single dose DSR study design & results

The investigator-initiated study (clinicaltrials.gov NCT03801226) was conducted by Dr. Testani at Yale University, in 10 patients receiving peritoneal dialysis (PD) who underwent randomisation and crossover to DSR infusate (a sodium-free solution) or standard PD solution. One litre of either DSR infusate or standard PD solution was infused into the peritoneal cavity and left to dwell for two hours before being removed. The patient repeated the procedure with the alternate solution one week later.

DSR therapy was safe and well-tolerated during a single dose administration and met its primary endpoint of non-discontinuation of the protocol due to discomfort or adverse events, with similar tolerability to standard PD solution. Sodium removal with DSR was substantial, equating to approximately five grams (which is 2.5 days of dietary sodium) removed with a single two hour treatment, and significantly higher (p<0.0001) than what is achievable with standard PD solutions. Unlike what is typically seen with loop diuretics, the inter-patient variability was very low with DSR therapy. The fluid removal through ultrafiltration was also higher with DSR compared to standard PD solution (p<0.0001). As a result of the convincing positive and consistent results between patients, the study could be halted after ten subjects (initially planned for up to 20 subjects).

Individual safety parameters such as change in blood pressure, plasma potassium, bicarbonate, calcium and magnesium were similar between both solutions (p>0.35 for all). There was a borderline significant 1 mmol/L decrease in serum sodium from baseline to 120 minutes in the DSR group (p=0.05) but this resolved by 60 minutes after draining the solution (p=0.34). Plasma glucose increased with both DSR and standard PD solution (p<0.3 for both), but this was not different between solutions at 120 minutes (p=0.08). There was negligible removal of off-target non-sodium electrolytes such as potassium, magnesium, phosphorus and calcium with DSR.