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Gastroesophageal Reflux Disease (GERD)

November 23, 2009

Addex reported positive results from a phase IIb trial of ADX-10059 for the treatment of gastroesophageal reflux disease (GERD). This double-blind, placebo-controlled, multi-center study enrolled 103 subjects in Europe known to respond well to proton pump inhibitors. There would be a two week baseline symptom evaluation period followed by two weeks of administration of ADX10059 120 mg twice daily. The primary endpoint was the patient reported number of GERD symptom free days in week 2 of treatment compared to the last 7 days of baseline. 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). ADX10059 also showed statistical superiority over placebo for secondary endpoints, including an increase in heartburn free days, a reduction in sleep disturbance, a reduction in the requirement for antacid medication, an improvement in a GERD symptom patient reported outcome questionnaire (p<0.05 for all measures). ADX-10059 was well tolerated.

March 31, 2008

Orexo reported positive results from a phase II trial of OX17 for the treatment of gastroesophageal reflux disease (GERD). This controlled trial enrolled fifty-nine subjects in Sweden. The subjects received OX17, omeprazole or famotidine for fourteen days. The primary endpoint was the reduction of acid production between the treatment arms. OX17 significantly reduced the acid production compared to omeprazole on day one. The time with pH>4 the first twelve hours after dosing was on average 60% longer with OX17 compared to omeprazole (p<0.05). After fourteen days treatment with OX17, the time with gastric pH>4 was twice as long as after treatment with famotidine. In addition, the need for rescue medication (antacids) during the fourteen day study period was considerably lower for OX17 compared to both famotidine and omeprazole. Based on the results, Orexo plans to move ahead with the development of OX17.

September 17, 2007

XenoPort announced positive results from a phase I trial of sustained release XP19986 (SR3) for the treatment of Gastroesophageal Reflux Disease (GERD). This trial enrolled 48 subjects who were placed into four separate cohorts to receive placebo or XP19986. Following an up-titration period, the first cohort received 30 mg once per day (QD) of XP19986 for seven days, followed by 30 mg twice daily (BID) for seven days and ending with a down-titration period. Subsequent cohorts received 60 mg and 90 mg QD and BID following a similar protocol. The final group of subjects received 120 mg QD only. Treatment was well tolerated with no unexpected adverse events. Results revealed that repeated once-daily dosing of XP19986 led to sustained levels of racemic (R) baclofen in blood over 24 hours, reaching steady state in three days. Repeated twice-daily dosing reduced the steady-state peak-to-trough ratio of R-baclofen by approximately 50% compared to QD dosing. Exposure to R-baclofen increased linearly with dose. Based on the results XenPort plans to commence phase II trials before the end of 2007.

June 11, 2007

Dynogen released positive results from a phase Ib trial of DDP733 for the treatment of nocturnal gastroesophageal reflux disease (nGERD). This double-blinded, placebo controlled trial enrolled healthy subjects who were given a high fat meal to induce gastroesophageal reflux. Reflux events were measured by intraesophageal impedance. The primary endpoint was a statistically significant reduction in the number of NGERD events over placebo. This was achieved in subjects receiving a DDP73 dose of 0.5 mg. Treatment was safe and well tolerated. Based on the results, Dynogen is planning to initiate phase II trials in 2008.

April 23, 2007

Addex issued positive results from a phase IIa trial of ADX10059 for the treatment of gastro-esophageal reflux disease (GERD). This single-blind, placebo-controlled trial enrolled 24 subjects. On Day 1 subjects received placebo, while on Day 2 they received ADX10059 (50 mg or 150 mg) half an hour before each of three meals. The primary objectives were to evaluate the effect of ADX10059 on physiological measures of reflux, using continuous 24-hour pH recording in the lower esophagus, and on the occurrence of patient-recorded clinical symptoms of GERD. Statistical significance was reached in the ADX10059 150 mg treatment group compared to placebo in the percentage of time that esophageal pH was greater than 4 during the 24-hour period (p = 0.014) as well as in the duration of acid reflux episodes (p = 0.013). Night time reflux was also significantly reduced by ADX10059 (p = 0.0021). In addition, while on placebo subjects experienced an average of 7 symptomatic episodes each lasting an average of 14 minutes. These were reduced to an average of 2 episodes each lasting 5 minutes during treatment with 250mg ADX10059. Based on the results Addex is in the process of designing phase IIb trials.

October 30, 2006

ChemoCentryx announced positive results from a phase II trial of Traficet-EN for the treatment of Crohn's disease. This trial enrolled 74 subjects who were randomized on a 2:1 basis to receive 250 mg of Traficet-EN or placebo, once daily for 28 days. Treatment was well tolerated. After 28 days the subjects receiving Traficet-EN had a mean decrease in C-reactive protein (CRP) blood levels of 4.4 +/- 3.7 mg/L while the subjects in the placebo group had a mean increase in CRP blood levels of 6.7 +/- 4.2 mg/L. In addition, in a defined subgroup of subjects in active flare at the time of treatment, 56% of those treated with Traficet-EN had a decrease on the Crohn's Disease Activity Index (CDAI) of 70 points versus 29% of the subjects on placebo. Overall a 100-point drop in CDAI scores occurred in 40% of those in the treatment group compared to 21% on placebo. ChemoCentryx is continuing development of Traficet-EN in ongoing phase II trials.

Osiris Therapeutics announced positive results from a phase II study of Prochymal for the treatment of moderate to severe Crohn's disease. This randomized, open label trial enrolled 10 subjects who were divided into two groups and received either low dose (2 million cells per kilogram) or high dose (8 million cells per kilogram) of Prochymal. Subjects were then evaluated for changes in the Crohn's Disease Activity Index (CDAI) and the Inflammatory Bowel Disease Questionnaire (IBDQ). Treatment was well tolerated with no serious adverse events reported. Within 14 days of treatment, one third of the subjects had a mean reduction in the CDAI of 105 by day 28, from 341(baseline) to 236 (p=0.004). Mean IBDQ scores improved significantly from baseline to day 28 (113 to 146, p=0.008). In addition there appeared to be a correlation between dose and response, with those receiving the higher dose of Prochymal achieving a 72 point greater reduction in CDAI than those receiving low dose (CDAI reduction of 137 vs. 65). Osiris is in the process of developing and implementing a phase III program.

Xenoport reported positive results from a phase IIa trial of XP19986 for the treatment of gastroesophageal reflux disease (GERD). This single-dose, randomized, double-blind, placebo-controlled, cross-over trial enrolled subjects who received 10, 20, 40 or 60 mg single doses of XP19986 or placebo, in separate test periods with four to seven days between testing periods. On testing days reflux-provoking meals were consumed at two hours and six hours after dosing, and subjects were required to lie on their right side for two hours after each meal. Reflux was monitored continually for 12 hours using a pH/impedance probe placed in the esophagus. The median number of total reflux episodes over 12 hours after placebo treatment for the combined dose groups was 50.5 (N=44). The median change in total reflux episodes after XP19986 treatment compared to placebo treatment was -9.5 (p=0.0050). Statistically significant reductions in acid reflux episodes were seen in both the 40 mg (p=0.0498) and 60 mg (p=0.0039) dosing groups when compared to placebo in the 12 hours after treatment. XenoPort plans to move development of XP19986 forward.

July 18, 2005

XenoPort announced positive results of a phase I trial of their investigational R-baclofen Transported Prodrug XP19986, for the treatment of gastroesophageal reflux disease (GERD) and gastric spasticity. Preliminary safety data were positive, with no serious adverse events reported with an immediate release (IR) formulation or two sustained release (SR) formulations of the drug. Overall adverse events for all three formulations were generally mild, and met the expected profile for baclofen administration. Pharmacokinetic data indicated that the drug was rapidly absorbed and metabolized into R-baclofen, with minimal systemic exposure to the prodrug. Both SR formulations yielded peak plasma concentrations and elimination half-lives consistent with a twice daily dosing schedule. The double-blind, placebo-controlled, single-dose study was conducted in two stages: the first used a dose escalating design to investigate 3 doses (2 mg, 4 mg or 8 mg) of IR XP19986 in 10 subjects; the second used a randomized, cross-over design to investigate the IR formulation and both SR formulations in separate cohorts of 10 subjects, each of whom received a single-dose of each formulation one week apart. Based on these results, the company announced plans to initiate additional phase I trials and a phase IIa trial later in 2005.