The primary endpoint of the study is to support dose selection of linaprazan glurate for phase III studies, through central assessment of four-week endoscopic healing of eGERD, with safety and tolerability as secondary endpoints. The study design included four dose levels of linaprazan glurate and one dose of the active comparator lansoprazole, a proton-pump inhibitor (“PPI”). Two separate cohorts of patients were enrolled, one cohort with patients having moderate to severe eGERD, defined as LA grade[1] C/D, and one with patients having milder eGERD, LA grade A/B, with a history of prior insufficient PPI-treatment.
 
Results

• For patients with moderate to severe eGERD, LA grade C/D, the highest four-week healing rate in a linaprazan glurate dosing group was 89%, compared to 38% in the lansoprazole group.

• While the study was not powered to demonstrate significance towards the comparator lansoprazole, the healing rate of all C/D patients treated with linaprazan glurate was significantly higher than lansoprazole in a post-hoc analysis (Fisher’s exact test, mean harmonic p-value= 0.0404).

• For all patients treated with linaprazan glurate, the mean healing rate was 80% compared to 69% in the lansoprazole treated group.

• For patients with milder eGERD, LA grade A/B, the highest four-week healing rate in a linaprazan glurate dosing group was 91%, compared to 81% in the lansoprazole group. 

• Linaprazan glurate was generally well tolerated and safety data was comparable to that of lansoprazole, with the most reported adverse event being COVID-19, occurring in 4% of the total study population.

"Delivering this higher healing rate, 89% versus 38%, combined with a good safety profile, for our primary patient population, moderate to severe eGERD patients, already after four weeks, compared to lansoprazole is a great achievement, especially in a market where most patients are given an eight-week healing course. The results from the LEED study give us confidence in planning the upcoming phase III program and are an important step towards driving a paradigm shift in the treatment of gastric acid related diseases," said Christer Ahlberg, CEO of Cinclus Pharma.
 
The favorable safety data together with a dose response pattern in the moderate to severe eGERD patient group, will, together with pharmacokinetic and pharmacodynamic data, provide a robust set of data for the selection of the optimal dose in the upcoming pivotal phase III program, expected to be initiated in the fall of 2023.
 
About the Linaprazan glurate Erosive Esophagitis Dose ranging (LEED) study
The LEED trial was conducted in the United States and Europe, including patients with erosive esophagitis (eGERD). Patients were divided into two cohorts, one with patients having moderate to severe eGERD (LA grade C/D) and one with patients having milder eGERD (LA grade A/B) with a history of prior insufficient PPI-treatment.
 
The primary endpoint of the study was to support dose selection of linaprazan glurate for the phase III program in eGERD, through central assessment of healing of erosive esophagitis after four weeks of treatment. The sample size, i.e. the number of patients needed, for measuring dose related efficacy was based on the patient cohort with moderate to severe eGERD.
 
After initial endoscopy and other screening procedures, 248 patients were randomized equally into one of five treatment groups, receiving either four weeks treatment with linaprazan glurate in four dose levels, or four weeks lansoprazole in the approved standard eGERD healing dose. Thereafter, an endoscopic evaluation of healing was performed, where healing was defined as no presence of esophageal erosions, i.e., no erosive damage to the esophageal mucosa.
 
After the endoscopic evaluation, all patient groups received lansoprazole for four weeks in a maintenance phase as requested by competent authorities. As per request from the competent authorities, a retrospective central review of the endoscopy findings was performed, and 162 patients were available for evaluation of the primary endpoint. All enrolled 248 patients were included in the safety analysis.

[1] The Los Angeles Classification of GERD.