Drug Development, Results

Ardelyx rolls out positive PhIII IBS-C data on tenapanor as rivals prep for a showdown, but shares crater

Two days ago it was Synergy Pharma’s turn to tout positive Phase III data on its drug Trulance for irritable bowel syndrome with constipation. Today, rival Ardelyx $ARDX is stepping up with the first of its two Phase III readouts on tenapanor as the newcomers look to challenge Ironwood’s market-leading therapy. And at first blush, investors weren’t impressed.

All but one of the key data points were all positive. In the primary goal, observing the impact of their drug in 6 of 12 weeks of therapy, 27% in the tenapanor arm scored a complete response on a significant 30% or greater reduction in abdominal pain and at least one added complete bowel movement from baseline — compared to 18.7% in the placebo group.

Mike Raab

Mike Raab

There was a key secondary miss, though, on individual bowel movement rates. Diarrhea could also prove troublesome for Ardelyx, with a relative rate of 14.6% for the drug arm vs 1.7% in the placebo group. 5.9% of the patients taking tenapanor discontinued due to diarrhea, but Ardelyx CEO Mike Raab has been hit before on diarrhea rates for this drug, and analysts are likely to be relieved the rate wasn’t higher.

Wedbush’s David Nierengarten looked the data over and concluded that the drug looked approvable, but not a top performer, landing “somewhere in between Linzess and Trulance (generally not as efficacious as Linzess or as well-tolerated as Trulance). Although we view product as approvable (assuming success in T3MPO-2, reading out next half) the results lower our estimates and partnership interest for the drug, particularly in light of the Trulance launch.”

That’s not what backers wanted to hear, and the biotech’s stock cratered, plunging 32%.

You can be sure the rivals — including the team marketing Ironwood’s Linzess — will seize on any shortcomings as they begin to square off over the market. Linzess has scored the highest of the three on efficacy (34%), with Ardelyx trailing in third place, though all are within a few points of each other. Linzess may have the worst rate for diarrhea.

None of these drugs stand out as a dominant drug on efficacy, and that may well lead to a near future scenario in which physicians send patients home with a sampling so they can decide which is best for them.

Trulance (plecanatide) investigator Ronald Fogel told me earlier in the week that that is what they do in his practice.

David Rosenbaum

“When we look at the totality of the topline results from T3MPO-1, we believe tenapanor has the potential to offer benefit to patients with IBS-C,” said David Rosenbaum, chief development officer at Ardelyx. “We are encouraged that the nine of 12 week data demonstrate a durable and sustained response for constipation and abdominal pain, as well as a normalization of bowel movement frequency, for many patients. The individual CSBM responder rate from the six of 12 week analysis was the one secondary endpoint not met and those data are not consistent with the results from our previous clinical studies. We plan to assess these data alongside the results from T3MPO-2, our six-month Phase 3 study, to evaluate the total benefit that tenapanor may provide to patients with this extremely challenging condition.”


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RAPS Regulatory Convergence 2017