Ardelyx $ARDX is taking a second shot at making a badly needed good late-stage impression with their lead drug for irritable bowel syndrome with constipation, rolling out a new round of promising Phase III data for their lead drug tenapanor.
In a tough field like IBS-C, impressing analysts is no easy task. But at first blush investors loved the news, driving up shares 56% this time.
When Ardelyx execs rolled out their first round of Phase III data on their IBS drug tenapanor, they were confident that they were playing a winning hand, with statistically significant results in beating out a placebo for easing abdominal pain and increasing bowel movements.
They were wrong.
Its shares were crushed after some analysts could barely stifle a yawn over perfectly approvable data that didn’t measure up so well against new data from a rival drug from Synergy $SGYP called Trulance as well as Ironwood’s franchise $IRWD drug Linzess. The setback was so severe, Fremont, CA-based Ardelyx shortly afterwords triggered a painful restructuring that cost a large number of jobs.
In the first go around, the top line primary endpoint hit 27.0% vs 18.7% drug-vs-placebo (p=0.02) for patients who had at least a 30% 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. This second time around, the number hit a much better rate: 36.5% vs. 23.7%, with a better p value of <0.001.
And the drug also hit all secondary endpoints on this turn.
“Of all the trials we’ve run, from Phase IIb, these are the kinds of results we anticipated,” CEO Mike Raab told me in a preview of the post-market close announcement. “It positions us extremely well going forward.”
It always causes a bit of a kerfuffle every time someone compares data from different drug studies, but that’s exactly what’s happening here. And this time around that 36.5% figure should help make Ardelyx’s case on efficacy alongside its rivals, which are fielding guanylate cyclase-C agonists. Ardelyx’s drug uses a novel mechanism involving the inhibition of sodium absorption.
Compare tenapanor to Linzess — 34% (Study 1) and 34% (Study 2) of Linzess-treated patients were combined responders, versus 21% (Study 1) and 14% (Study 2) of placebo-treated patients.
And then Synergy’s Trulance: 30.2% in 3 mg and 29.5% in 6 mg dose groups compared to 17.8% in placebo; p<0.001 for 3 mg and p<0.001 for 6 mg; Study 2: 21.5% in 3 mg and 24.0% in 6 mg dose groups compared to 14.2% in placebo; p=0.009 for 3 mg and p<0.001 for 6 mg.
Diarrhea as a too-common side effect remains an issue for Ardelyx, with a rate of 16.0% vs. 3.7% for the drug compared to the placebo arm. But investigators also pointed to a statistically significant set of responses for 9 of 12 weeks, with a greater likelihood of a more normal rate of bowel movements among a portion of the patients in the study.
“The thing that patients wanted was not just a complete bowel movement,” says chief development officer David Rosenbaum. “They wanted to get into the normal range. If they have an increase in 1 that’s good, but in a normal range, from three bowel movements a week to three a day,” that’s much better.
The Phase III isn’t completely done yet. There’s a safety extension study that has to wrap. But then the company believes it will be set up to complete their application and get it in front of regulators in the second half of next year, where they stand a good chance of getting an approval in 2019.
This second Phase III also improves Ardelyx’s position in lining up key commercial partners, says Raab.
Adds Raab: “Now we’ll see how the market reacts.”
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