It's been a busy September for Ardelyx Inc. so far. Less than two weeks after the Fremont, Calif-based company reported promising pivotal data for tenapanor in chronic kidney disease patients with hyperphosphatemia, the sodium hydrogen exchanger 2 (NHE3) inhibitor won FDA approval for use in irritable bowel syndrome with constipation (IBS-C).
The FDA nod, coming on the Sept. 12 PDUFA date, was widely expected, given the stellar phase III data reported for tenapanor, now branded Ibsrela, in late 2017, which showed statistical significance for the primary endpoint and all secondary endpoints evaluated in the top-line results. The primary endpoint, combined responder rate (CRR) for six of 12 weeks, showed that a greater proportion of tenapanor-treated patients compared to those given placebo (36.5% vs. 23.7%, p<0.001) had at least a 30% reduction in abdominal pain and an increase of one or more complete spontaneous bowel movements (CSBMs) in the same week for at least six of the 12 weeks of the treatment period. Well-tolerated, tenapanor also made the statistical grade for CSBM and abdominal pain responder rates in the six of 12 and nine of 12 treatment weeks, with a consistent response across all 26 weeks of the study. (See BioWorld, Oct. 12, 2017.)
The earlier phase III study also hit its primary endpoint. In both trials, the proportion of responders for nine of the first 12 weeks, including at least three of the last four weeks, was greater in the tenapanor-treated patients vs. placebo. Also in both trials, improvements from baseline in average weekly CSBMs and abdominal pain were observed by week one, with improvements maintained through the end of treatment.
Inhibiting the NHE3 transporter is designed to reduce the absorption of dietary sodium in the bloodstream. That results in more sodium in the gut, which boosts fluid and loosens stool.
Ardelyx, which has estimated 11 million people in the U.S. suffering from IBS-C, will face competing products already on the market from Ironwood Pharmaceutical Inc.'s Linzess (linaclotide) and Synergy Pharmaceuticals Inc.'s Trulance (plecanatide). But the company doesn't plan to launch on its own; instead, its aim is to find a commercial partner to handle launch and commercialization activities, though the company provided no timeline for reaching an agreement.
Ardelyx terminated a previous deal with Cambridge, U.K.-based Astrazeneca plc, in 2015, buying back the rights to tenapanor and the rest of its NHE3 portfolio under an approving eye from Wall Street. (See BioWorld, June 4, 2015.)
Meanwhile, the focus on tenapanor goes beyond IBS-C. The drug, which also works to reduce paracellular uptake of phosphate, is being tested in CKD patients with hyperphosphatemia on dialysis. Data reported earlier this month from the phase III Amplify trial in patients whose conditions are not adequately controlled by phosphate binders showed the study met all key primary and secondary endpoints. Patients treated in tenapanor arm, in combination with phosphate binders, had a statistically significant mean reduction in serum phosphorus from baseline to the end of the four-week treatment period vs. those treated in the binder-only arm (0.84 vs. 0.19, p=0.0004).
Those in the tenapanor arm also showed statistically significant decreases in serum phosphorus during all four weeks (p<0.0004). And up to 49.1% of patients treated with tenapanor plus a binder achieved a serum phosphorus of <5.5 mg/dL, compared to 23.5% of patients treated with a binder alone (p≤0.0097).
A second phase III readout is expected by year-end, from the Phreedom trial, testing tenapanor as a monotherapy in hyperphosphatemia in patients with end-stage renal disease (ESRD) who are on dialysis. Pending positive results, an NDA submission could follow in early 2020, with potential market launch in ESRD hyperphosphatemia in early 2021.
"These catalysts, along with a potential partnership in IBS-C ... make for an eventful period for ARDX and we remain buyers," noted Piper Jaffray's Christopher Raymond in a Sept. 3 research report.
Ardelyx shares (NASDAQ:ARDX) closed Thursday at $6.28, up 48 cents.