Ibsrela (US)Irritable bowel syndrome, constipation-predominant
New molecular entity
Development and Regulatory status
Phase III Clinical Trials
Phase III Clinical Trials
Licensed but not launched
Nov 21Ardelyx plans to launch tenapanor in US for IBS in the second quarter of 22 
May 20Tenapanor has not yet been launched in the US. To efficiently bring its treatments to market, Ardelyx is pursuing strategic collaborations for Ibsrela for IBS-C and tenapanor for hyperphosphatemia in certain territories. Ardelyx has established agreements with Kyowa Kirin Company Limited in Japan, Fosun Pharma in China and Knight Therapeutics in Canada .
May 20In its latest quarterly report, Ardelyx does not report that it has signed any collaboration and licence agreements with other companies to market tenapanor in the EU. Latest plans for EU development unknown .
Sep 19Approved in US for treatment of IBS with constipation (IBS-C) .
Sep 18NDA filed in US .
Mar 18In its annual 10K form, Ardelyx states its ambition to build a multi-product company that commercializes its renal products (including tenapanor) in the US & to leverage ex-U.S. collaborations with established industry leaders to efficiently bring our renal medicines to patients outside the US. An agreement has been reached with Fosun Pharma to develop & commercialise tenapanor for IBS in China. No agreements have yet been signed with European companies for tenapanor for any indication .
First-in-class inhibitor of gastrointestinal NHE3 sodium transporter reduces dietary sodium absorption, more fluid in gut.
IBS occurs in 10-20% of the population in the UK, but prevalence is thought to be higher than this as many people with the disorder do not seek medical advice. Approximately one third of patients have IBS with constipation (IBS-C) = loose stools 25% of the time .
Irritable bowel syndrome, constipation-predominant
Trial or other data
Jan 18Ardelyx report safety trial data from an extension study. Study found that 9.2% of patients experienced diarrhoea, with 1.7% discontinuing treatment due to this adverse reaction .
Oct 17Further PIII data announched by Ardelyx from the ongoing T3MPO2 study (NCT02686138) for tenapanor vs. placebo. The 26-week, randomised, double-blind, placebo-controlled, study is evaluating the safety and efficacy tenapanor (50mg BD or matched placebo) in 600 pts with constipation-predominant IBS. Tenapenor achieved a 36.5% combined responder rate in the latest TEMPO2 study compared to 23.7% for placebo, compared to 27% and 19% respectively in the earlier TEMPO 1 trial, and the effects were sustained throughout the 26-week trial period. The rate of diarrhoea reported in this study was 12% [3,4].
May 17PIII T3MPO-1 trial (n=610) achieved statistical significance for the primary endpoint and seven of eight secondary endpoints. The primary endpoint, the combined responder rate for six of 12 weeks, showed that a greater proportion of tenapanor-treated patients (50mg bd) compared to placebo-treated (27.0% vs 18.7%, p=0.02) had at least a 30 percent reduction in abdominal pain and an increase of one or more complete spontaneous bowel movements (CSBM) in the same week for at least six of the 12 weeks of the treatment period . 22/05/2017 15:56:23
Evidence based evaluations
Ibsrela (US)Hyperphosphataemia in patients with chronic kidney disease (CKD) on dialysis
Licence extension / variation
Development and Regulatory status
Not recommended for approval (Negative opinion)
Apr 22The FDA has agreed to convene the Cardiovascular and Renal Drug Advisory Committee to consider the second level appeal application from Ardelyx. The FDA believes input from the committee would be valuable in considering the clinical meaningfulness of the phosphate-lowering effect seen with tenapanor during a PIII trial. The FDA Office of New Drugs will then have 30 days from the meeting to respond to Ardelyx ´s appeal. No date has been set for the meeting .
Feb 22Company has received an Appeal Denied Letter by the FDA 
Nov 21Company plan to formally challenge the FDA CRL with a formal dispute 
Oct 21Following a meeting with the FDA, Ardelyx has announced they still do not have the clarity they needed from the FDA to move forward with the new drug application for tenapanor for the control of serum phosphorus in chronic kidney disease patients on dialysis, and is therefore forced to reduce its workforce by approximately 65% (102 employees) .
Jul 21FDA issues complete response letter for tenapanor. Whilst the submitted data provided substantial evidence that tenapanor is effective in reducing serum phosphorous in CKD patients on dialysis the effect was small and of unclear significance. The FDA have suggested an additional clinical trial would be required before approval .
Jul 21US FDA write to Ardelyx ahead of PDUFA evaluation date (July 29, 2021) citing "deficiencies" found in its evaluation of tenapanor for CKD. The FDA say they have found an issue with the "size of the treatment effect and clinical relevance" of tenapanor. The FDA noted that its letter did not mean denial, as tenapanor is still being reviewed. 
Jun 20Filed in US .
Dec 19Company announced plans to submit NDA to the US FDA in mid-2020.
First-in-class inhibitor of gastrointestinal NHE3 sodium transporter reduces dietary sodium absorption which causes a reduction in phosphate uptake. Paracellular phosphate permeability is reduced by tenapanor.
Hyperphosphataemia occurs because of insufficient filtering of phosphate from the blood by poorly functioning kidneys. High serum phosphate levels can directly and indirectly increase PTH secretion, leading to secondary hyperparathyroidism. Left untreated, secondary hyperparathyroidism increases morbidity and mortality and may lead to renal bone disease with bone and muscular pain, increased incidence of fracture, bone and joint abnormalities and vascular and soft tissue calcification .
Hyperphosphataemia in patients with chronic kidney disease (CKD) on dialysis
Trial or other data
Dec 19Data reported from the PIII PHREEDOM trial (NCT03427125) in which pts were randomised 3:1 to tenapanor 30mg with dose adjustments based on serum phosphorus level and gastrointestinal tolerability (n=423, n=408 ITT) or sevelamer as per licensed dose (n=141) for 26 weeks. At the end of the 26-week treatment period, pts on tenapanor were randomised 1:1 to enter the randomised withdrawal period and remain on the tenapanor dose they were taking or receive placebo for 12 weeks. After this, pts continued 3 months as part of the long-term safety extension. Patients on sevelamer were allowed dose changes at the discretion of the principal investigator for up to 1 year. The primary efficacy endpoint (difference in change in serum phosphorus between the pooled tenapanor-treated pts and placebo-treated pts in the efficacy analysis set from the end of the 26-week treatment period to the endpoint visit of the 12-week randomised withdrawal period) was -1.4 mg/dL, p<0.0001 vs. placebo. During the 26-week treatment period, 77% of tenapanor-treated pts in the ITT population (n=408) had a mean reduction from baseline of 2.0 mg/dL in phosphorous level. Tenapanor was generally well-tolerated, the most common adverse event was mild to moderate diarrhea in 52.5% of pts. Compared to sevelarmer, 7.2% of tenapanor-treated pts experienced serious adverse events vs. 22.6% of sevelamer-treated pts (thr median dose for tenapanor was 60mg/day and for sevelamer, it was 7.2g/day. It is worth noting that the tenapanor label for the treatment of IBS with constipation carries a boxed warning for risk of serious dehydration in children in the US. 
Sep 19Topline data from PIII AMPLIFY trial showed that primary endpoint was met. Pts treated with PO tenapanor (n=116) showed a statistically significant (p=0.0004) mean reduction in serum phosphorus from baseline to the end of the 4-week treatment period of 0.84 mg/dL vs. placebo arm (n=119) who had a mean reduction of 0.19 mg/dL. Pts in the tenapanor arm had statistically significant decreases in serum phosphorus during all 4 weeks ranging from 0.84 to 1.21 mg/dL (p < 0.0004). Up to 49.1% of pts achieved a serum phosphorus of <5.5 mg/dL with treatment vs. 23.5% in the binder arm (p=0.0097). There was a statistically significant 22% to 24% reduction (p=0.0027) in FGF23 levels in the tenapanor arm placebo. 
Jun 19PIV NORMALIZE, open label, non-randomised trial (NCT03988920) started to assess the ability of tenapanor alone, or with sevelamer to achieve target serum phosphorus concentration, in pts with end-stage kidney disease on dialysis. The trial intends to enrol ~150 pts including pts who have completed the PIII PHREEDOM trial.[3,6]
Mar 19Ardelyx will add an active control arm to PHREEDOM trial for safety evaluation puposes.
Feb 19PIII AMPLIFY randomised, double-blind, placebo-controlled trial (NCT03824587) started. This will evaluate the efficacy of tenapanor as an adjunct to phosphate binder therapy, in end-stage renal disease (ESRD) pts (n = ~236) with hyperphosphataemia . The primary and secondary endpoints are designed to determine a change in serum phosphorus (s-P) level from baseline and at week 4.[2,3,5]
Jan 18PIII open, parallel, prospective, randomised PHREEDOM trial (NCT03427125) initiated of tenapanor for treatment of hyperphosphataemia in ~564 pts with end-stage renal disease, who were on dialysis. The trial will comprise of a 26-week randomised treatment period, followed by an up to 12-week, double-blind, placebo-controlled, randomised withdrawal period with an open-label extension. [2-4]