TAK-390MR Phase 3 Data Presented At Digestive Disease Week

TAP Pharmaceutical Products Inc. have reported results from three pivotal Phase 3 studies evaluating investigational new drug TAK-390MR, the first proton pump inhibitor (PPI) with an innovative dual delayed release technology, in healing patients with erosive esophagitis (EE) and in maintenance of healed EE. The data were presented at the Digestive Disease Week (DDW) annual meeting in San Diego.

"The innovative dual delayed release technology delivers TAK-390MR in two separate releases, which is a first in the PPI class and makes TAK-390MR a very interesting potential future treatment option," said Dr. David Peura, professor of medicine, University of Virginia Health System, past president of the American Gastroenterological Association.

Data from the two separate EE healing studies demonstrated that patients treated with TAK-390MR 60 mg and 90 mg experienced higher overall healing after eight weeks, versus patients taking lansoprazole 30 mg. In addition, data from a six-month maintenance of healed EE study demonstrated that patients treated with TAK-390MR 30 mg and 60 mg experienced statistically significant overall maintenance and symptom relief over placebo.

Healing of Erosive Esophagitis Studies

TAK-390MR was compared to lansoprazole in two identically designed, double-blind, randomized, controlled trials in patients with confirmed EE. A total of 4,092 patients were enrolled in the two global studies. The primary objective was to evaluate overall healing rates over eight weeks after once-daily administration of TAK-390MR 60 mg or 90 mg or lansoprazole 30 mg. The results for each study were analyzed using life table and crude rate methods.

Results from these trials demonstrated that TAK-390MR 60 mg and 90 mg produced consistently high healing rates for patients with EE. In one study, the life table analysis showed that 93 percent and 95 percent of TAK-390MR patients (60 mg and 90 mg, respectively) experienced healing versus 92 percent of lansoprazole 30 mg patients. The crude rate analysis showed that 87 percent of 60 mg and 89 percent of 90 mg TAK-390MR patients experienced healing versus 85 percent of lansoprazole 30 mg patients.

In a second study, the life table analysis demonstrated that 92 percent of both 60 mg and 90 mg patients experienced healing versus 86 percent of patients on lansoprazole 30 mg. The crude rate evaluation showed that 85 percent and 86 percent of patients treated with TAK-390MR (60 mg and 90 mg, respectively) experienced healing versus 79 percent of patients taking lansoprazole 30 mg. The results for TAK-390MR 90 mg were statistically significantly higher than lansoprazole 30 mg in both studies using crude rate analysis.

The most frequent treatment-related adverse event (AE) for patients in the combined healing studies was diarrhea, which occurred in similar rates across groups (three percent for TAK-390MR 60 mg and 90 mg, versus two percent for lansoprazole 30 mg).

"Findings from both studies demonstrated that patients taking TAK-390MR 60 mg and 90 mg showed numerically higher overall healing than those taking lansoprazole with a similar rate of AEs across groups," said Dr. Prateek Sharma, professor of medicine, gastroenterology section, University of Kansas School of Medicine.

Maintenance of Healed Erosive Esophagitis

TAK-390MR was compared to placebo in a double-blind, randomized, controlled trial in patients with confirmed healing of EE. A total of 445 patients were enrolled in the global, six-month study. The primary objective was to evaluate the overall maintenance rate of healed EE after once-daily administration of TAK-390MR 30 mg, 60 mg, or placebo. A secondary objective was to evaluate the frequency of heartburn over the six-month study.

Results from the trial showed that TAK-390MR 30 mg and 60 mg produced high maintenance rates for patients with healed EE. Maintenance rates were analyzed using both life table and crude rate analyses.

The life table analysis showed that 75 and 83 percent of patients (30 mg and 60 mg respectively) were maintained over six months versus 27 percent of those patients taking placebo. According to the crude rate analysis, 66 percent of patients taking TAK-390MR 30 mg and 60 mg were maintained over six months versus 14 percent on placebo.

TAK-390MR also demonstrated heartburn relief rates during the six month trial. Patients treated with TAK-390MR were heartburn free a median of 99 and 96 percent of nights (30 mg and 60 mg respectively) versus 71 percent of nights for patients treated with placebo. In addition, patients treated with TAK-390MR were heartburn free a median 96 and 91 percent of 24-hour days (30 mg and 60 mg, respectively) versus 29 percent of 24-hour days for patients treated with placebo.

The most frequent treatment related AEs for patients in the six-month maintenance study taking TAK-390MR included flatulence, bloating and distension (2%), diarrhea (2%), dyspeptic signs and symptoms (1%), gastritis (1%), and nausea/vomiting (1%) and were generally similar to placebo.

"The heartburn relief rates are encouraging, particularly when you consider that they reflect symptom relief during the complete 24-hour period," said Dr. David Metz, professor of medicine, University of Pennsylvania School of Medicine. "These maintenance results coupled with the overall healing results are encouraging for the potential of TAK-390MR in treating patients with gastroesophageal reflux disease."

About TAK-390MR

TAK-390MR, an enantiomer of lansoprazole, employs an innovative dual delayed release technology, which is designed to provide two separate releases of drug for extended duration of acid suppression.

These Phase 3 data are part of the new drug application (NDA) filed in December 2007 for TAK-390MR for the treatment of patients with symptomatic GERD, the healing of erosive esophagitis, and the maintenance of healed erosive esophagitis. The NDA was based on global studies conducted in more than 20 countries evaluating approximately 6,000 subjects with erosive and non-erosive GERD.