Addex ADX10059 Monotherapy is Effective on GERD Symptoms in Phase IIb Clinical Trial
Addex Pharmaceuticals announced that it achieved statistically significant efficacy on the primary endpoint, increasing the number of symptom free days in the Phase IIb trial of ADX10059 as a monotherapy in patients with gastroesophageal reflux disease (GERD), the cause of heartburn and other symptoms. ADX10059 is a first-in-class reflux inhibitor that works by reducing activation of the metabotropic glutamate receptor 5 (mGluR5) through negative allosteric modulation (NAM). This approach may lead to a new class of drugs that addresses the causes of GERD rather than just the symptoms.
Chief Medical Officer Charlotte Keywood said: "We saw the number of symptom free days increase by five-fold, an exciting and clinically meaningful effect for ADX10059 monotherapy. The magnitude of the effect, along with the tolerability profile, indicate that ADX10059 has potential to be a useful therapy for GERD management."
"Based on its marked efficacy in both reducing reflux and controlling symptoms in this study, I would be pleased to see ADX10059 tested in later stage trials as a monotherapy for GERD patients," said professor Frank Zerbib, head of gastroenterology at the University Hospital of Bordeaux. "Furthermore, the good tolerability seen with this modified-release formulation of ADX10059 was also a crucial part of these results, since GERD is a chronic disease where long-term therapy is needed in the majority of patients."
Study ADX10059-204 was a double-blind, placebo-controlled, multi-center European Phase IIb trial in 103 GERD patients known to respond well to proton pump inhibitors (PPIs). There was a two-week baseline symptom evaluation period followed by two weeks of administration of ADX10059 120 mg twice daily. ADX10059 was used as a monotherapy so patients in the study did not use PPIs or other acid suppressant therapy during the baseline and study treatment periods. The primary clinical endpoint was the patient reported number of GERD symptom free days in week 2 of treatment compared to the last 7 days of baseline. Objective measures of the effects of ADX10059 on esophageal function and reflux events were made in a subset of 24 patients on the day before starting treatment and on the last day of treatment using impedance pH monitoring and esophageal manometry. Reflux events on impedance pH monitoring were the mechanistic primary variables.
ADX10059 significantly increased the mean number of GERD symptom free days in week 2 of treatment. At baseline the mean number of symptom free days was 0.46 in the ADX10059 group and 0.72 days in the placebo group. During treatment week 2 this increased to 2.5 days in the ADX10059 group and to 1.71 days in the placebo group (p = 0.0452)
In the subset of 24 patients who underwent mechanistic monitoring ADX10059 also achieved statistical significance in two mechanistic primary endpoints. ADX10059 significantly reduced total impedance measured reflux events and also acidic reflux events over the 24 hour monitoring period. In the ADX10059 treated group the mean number of total reflux events decreased by 26% from 64.9 at baseline to 47.9 on treatment compared to no change in the placebo group with a mean of 77.0 reflux episodes at baseline and 78.4 on treatment (p = 0.0342). In the ADX10059 group the mean number of acidic reflux events in 24 hours decreased by 29% from 52.1 at baseline to 37.0 at end of treatment compared to a small increase in the placebo group with 55.7 episodes at baseline, and 59.7 at end of treatment (p = 0.0032).
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