Ardelyx Receives FDA Approval for IBSRELA® (Tenapanor), an NHE3 Sodium Transport Inhibitor, for the Treatment of Irritable Bowel Syndrome with Constipation
"IBSRELA has the potential to provide IBS-C patients and their doctors with a novel mechanism and an innovative approach to managing IBS-C, a highly burdensome and difficult-to-treat condition affecting more than 11 million people in
Mr. Raab continued, "With the approval of IBSRELA for IBS-C, along with the successful completion of our AMPLIFY trial in hyperphosphatemia, we've delivered on two major corporate milestones in the last two weeks due to flawless execution by the remarkable and talented team at
IBSRELA (tenapanor) Phase 3 IBS-C Program
Phase 3 Study Designs
The Phase 3 IBS-C program included two randomized, double-blind, placebo-controlled trials. The trial designs were identical through the first 12 weeks of treatment, and thereafter differed in that Trial 1 (NCT02686138) continued for an additional 14 weeks of treatment (26 weeks double-blind treatment), whereas Trial 2 (NCT02621892) included a 4-week randomized withdrawal (RW) period (12 weeks double-blind treatment). Patients who were enrolled in these trials met the Rome III criteria for IBS-C, related to abdominal pain and bowel movement frequency.
The primary endpoint for both trials was the proportion of patients who were responders during the 12-week treatment period. A responder, as defined by the
In both Phase 3 IBS-C trials, IBSRELA met the primary endpoint as compared with placebo (Trial 1: 37% versus 24%, IBSRELA versus placebo, respectively. Trial 2: 27% versus 19% IBSRELA versus placebo, respectively).
In Trials 1 and 2, the proportion of responders for 9 out of the first 12 weeks, including at least 3 of the last 4 weeks, was greater in IBSRELA-treated patients compared to placebo-treated patients. In addition, in Trial 1, the proportion of responders for 13 out of 26 weeks was greater in IBSRELA‑treated patients compared to placebo-treated patients. In both trials, improvements from baseline in average weekly CSBMs and abdominal pain were observed by Week 1, with improvement maintained through the end of treatment.
In both studies, the most common adverse event was diarrhea (16% with IBSRELA vs 4% with placebo in Trial 1; and 15% with IBSRELA vs 2% with placebo in Trial 2), with severe diarrhea reported in 2.5% of IBSRELA-treated patients compared to 0.2% on placebo‑treated patients during the 26 weeks of Trial 1 and the 12 weeks of Trial 2. Overall discontinuation rates were low among patients treated with IBSRELA (7.6%) and placebo (0.8%) and the most common adverse reaction leading to discontinuation was diarrhea (6.5% of IBSRELA-treated patients compared to 0.7% of placebo-treated patients).
Indications and Usage
IBSRELA (tenapanor) is indicated for treatment of irritable bowel syndrome with constipation (IBS-C) in adults.
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS
IBSRELA is contraindicated in patients less than 6 years of age; in young juvenile rats, tenapanor caused death presumed to be due to dehydration. Avoid use of IBSRELA in patients 6 years to less than 12 years of age. The safety and effectiveness of IBSRELA have not been established in pediatric patients less than 18 years of age.
- IBSRELA is contraindicated in pediatric patients less than 6 years of age.
- IBSRELA is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction
Warnings and Precautions
Risk of Serious Dehydration in Pediatric Patients
IBSRELA is contraindicated in patients below 6 years of age. The safety and effectiveness of IBSRELA in patients less than 18 years of age have not been established. In young juvenile rats (less than 1 week old; approximate human age equivalent of less than 2 years of age), decreased body weight and deaths occurred, presumed to be due to dehydration, following oral administration of tenapanor. There are no data available in older juvenile rats (human age equivalent 2 years to less than 12 years).
Avoid the use of IBSRELA in patients 6 years to less than 12 years of age. Although there are no data in older juvenile rats, given the deaths in younger rats and the lack of clinical safety and efficacy data in pediatric patients, avoid the use of IBSRELA in patients 6 years to less than 12 years of age
Diarrhea was the most common adverse reaction in two randomized, double-blind, placebo-controlled trials of IBS-C. Severe diarrhea was reported in 2.5% of IBSRELA-treated patients. If severe diarrhea occurs, suspend dosing and rehydrate patient.
In the two IBS-C trials, the most common adverse reaction in IBSRELA-treated patients (incidence ≥2% and greater than in the placebo group) was diarrhea (Trial 1: 16% IBSRELA vs 4% placebo; Trial 2: 15% IBSRELA vs 2% placebo).
Please also see the full Prescribing Information, including Box Warning, for additional risk information.
About Irritable Bowel Syndrome with Constipation (IBS-C)
Irritable bowel syndrome with constipation (IBS-C) is a GI disorder in which abdominal pain is associated with constipation, and significantly affects the health and quality of life of at least 11 million people in the US. A study published in the
About IBSRELA for IBS-C
IBSRELA (tenapanor) is a locally acting inhibitor of the sodium/hydrogen exchanger 3 (NHE3), an antiporter expressed on the apical surface of the small intestine and colon primarily responsible for the absorption of dietary sodium. In vitro and animal studies indicate its major metabolite, M1, is not active against NHE3. By inhibiting NHE3 on the apical surface of the enterocytes, tenapanor reduces absorption of sodium from the small intestine and colon, resulting in an increase in water secretion into the intestinal lumen, which accelerates intestinal transit time and results in a softer stool consistency.
Tenapanor has also been shown to reduce abdominal pain by decreasing visceral hypersensitivity and by decreasing intestinal permeability in animal models. In rat model of colonic hypersensitivity, tenapanor reduced visceral hyperalgesia and normalized colonic sensory neuronal excitability.
Conference Call Information
The company will host a conference call today,
Forward Looking Statements
To the extent that statements contained in this press release are not descriptions of historical facts regarding
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