Small-cap biotech Ardelyx now has a second and more positive phase 3 trial for its constipation-predominant irritable bowel syndrome (IBS-c) drug tenapanor, setting up regulatory filings next year.
The NHE3 inhibitor nailed the confirmatory trial achieving all its primary and secondary outcome objectives including a significantly higher combined response rate—defined as a reduction in abdominal pain and an increase in spontaneous bowel movements—compared to placebo.
The new data sparked an 36% rise in the company’s share price after hours, although it was up nearly 60% at one point, which was the opposite of what occurred when it reported the results of its first phase 3 trial earlier this year.
Those results failed to impress investors, drawing out unfavorable comparisons with rival IBS-c therapies such as Ironwood Pharma’s already-approved Linzess (linaclotide) and Synergy’s Trulance (plecanatide) which is in late-stage testing. The data also came on the back of a string of setbacks with the drug including a failed trial in diabetics with chronic kidney disease and the loss of AstraZeneca as a development partner.
The fallout forced Ardelyx to cut staff and put some earlier-stage programs on hold to conserve resources as it gambled on tenapenor’s prospects in IBS-c and a follow-up indication, hyperphosphatemia in patients with end-stage renal disease on dialysis.
The new data are looking a lot better. 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 company also said that there was 12% rate of diarrhea with the drug in this study, a side effect that has previously caused investors to question its commercial potential, arguing that this compares favorably with Linzess.
“These results are game-changing for tenapanor as a product and Ardelyx as a company,” said the biotech’s CEO Mike Raab on a conference call, predicting a filing in the second half of 2018 and possible approval and launch the following year. He also said the new data will facilitate its ongoing search for a commercial partner.
“We are now one step closer to achieving our vision of bringing a first-in-class, highly differentiated treatment to underserved patients,” he continued, adding that tenapanor “will be a competitive product in the market.” Linzess and Trulance are both guanylate cyclase-C (GC-C) agonists, promoting gastrointestinal secretion, while tenapanor works by clearing excess sodium from the GI tract.
IBS-c is a challenging condition, with two-thirds of patients not responding to initial treatment, said Raab, who suggested tenapanor could eventually become a preferred first-line option for patients “who seek fast onset, sustained relief and the best chance for normalization of their bowel function.”
“We are confident that tenapanor will fill a void in today’s therapeutic options” in IBS-c, with potential in other indications such as chronic idiopathic constipation and opioid-induced constipation, he said.