On 11 October, Ardelyx reported positive results from a second pivotal Phase III trial (T3MPO-2) assessing the efficacy and safety of its lead product, tenapanor, which is under development for treatment of irritable bowel syndrome with constipation (IBS-C). In the US, the IBS-C space is currently dominated by Linzess (linaclotide) and Amitiza (lubiprostone), and GlobalData believes tenapanor is well positioned to compete for market share with the above brands and other generic offerings, assuming successful completion of the T3MPO-3 trial and expected submission of a New Drug Application (NDA) to the FDA in the second half of 2018.
Tenapanor is a first-in-class, small-molecule sodium–hydrogen exchanger 3 (NHE3) antagonist that exerts its therapeutic effect by inhibiting sodium absorption in the gut and subsequently increasing water levels retained in the lumen, leading to an increase in fecal fluid and improvement in bowel movements. The safety and efficacy of tenapanor is being assessed in a Phase III program (T3MPO) made up of two pivotal Phase III trials (T3MPO-1 and T3MPO-2) as well as an open-label, long-term safety trial (T3MPO-3).
Having failed to meet the secondary endpoint of improving individual bowel movement rates in the T3MPO-1 trial earlier this year, GlobalData believes the strong data from the T3MPO-2 study resurrects tenapanor’s chances for successful market entry. The primary endpoint of combined responder rate for six of 12 weeks demonstrated that compared with placebo (23.7%), 36.5% of tenapanor-treated patients had at least a 30% reduction in abdominal pain and an increase in one or more complete spontaneous bowel movements (CSBM) in the same week for at least six of the 12 weeks of the treatment period (p < 0.001).
However, the biggest downfall of all available IBS-C therapies is the increased incidence of diarrhea compared with placebo, and Asteryx’s tenapanor is no different (16.0% vs. 3.7%). The placebo-adjusted discontinuation rate due to diarrhea in the T3MPO-2 trial was 5.8%.
Nonetheless, tenapanor reached statistical significance for the CSBM and abdominal pain responder rates in the six of 12 and nine of 12 treatment weeks, respectively, with a consistent response across the 26 weeks of the study, which is indicative of normalized bowel movement and may be a major selling point for the drug.
With that said, tenapanor will provide a useful addition to the IBS-C treatment arsenal if approved, but it won’t be a game-changer. There remains an unmet need for IBS-C therapies with improved safety profiles, especially with regards to diarrhea. On entry, tenapanor will face competition from established players such as Linzess and Amitiza as well as two pipeline therapies, Trulance (plecanatide) and SYN-20, which GlobalData anticipates to enter the marketplace in the near future.
GlobalData (2017) Irritable Bowel Syndrome - Global Drug Forecast and Market Analysis to 2026, to be published