One down, two to go for Ardelyx. And success in the Amplify trial of tenapanor in hyperphosphataemia should give the project a better chance of making a mark than in its lead indication, constipation-predominant IBS.
So it is little wonder that Ardelyx’s stock jumped 71% yesterday on the data from Amplify, which evaluated tenapanor plus phosphate binders in patients uncontrolled on phosphate binders alone, though the stock was off 14% this morning. The data should also bode well for tenapanor monotherapy in hyperphosphataemia, where the Phreedom trial is set to read out in the fourth quarter.
Amplify met its primary endpoint, showing a significant reduction in serum phosphorus levels after four weeks of therapy with the combo versus control. It also met key secondary endpoints, finding that more patients in the combo arm achieved serum phosphorus of less than 5.5mg/dl, and that they had a greater reduction in FGF23, a marker of cardiovascular risk.
A win in this population should expand tenapanor’s potential market in patients with chronic kidney disease and hyperphosphataemia. The space is dominated by generic phosphate binders, but these contribute to a high pill burden; patients often take around 19 pills per day, with half of these phosphate binders.
The hope is that tenapanor, which was given twice daily in Amplify, can reduce the number of phosphate binders needed and improve compliance.
However, the big test will be Phreedom: Leerink analysts estimate that most of the project’s sales in hyperphosphataemia will come from monotherapy.
Phreedom has the same endpoint as Amplify, change in serum phosphorus, but measured after a 12-week withdrawal period. It is also testing twice-daily tenapanor, but could support the possibility of once-daily dosing if the drug continues to suppress phosphorus levels during withdrawal.
Still, tenapanor could soon be approved in a completely different indication, constipation-predominant irritable bowel syndrome (IBS-C), where it is due a US FDA decision by September 12 (Go or no go? Novo awaits call on oral sema, August 30, 2019).
The project is expected to get the go-ahead here, but it does not look any better than Allergan’s marketed constipation drug, Linzess, and tenapanor’s commercial chances could depend on it hooking a partner.
Currently, EvaluatePharma sellside consensus forecasts higher sales in IBS-C, although much of this is attributed to a potential partner.
Ardelyx, capitalised at around $300m, might now have a win under its belt, but success has been a long time coming for tenapanor, which was formerly partnered with Astrazeneca; based on EvaluatePharma Vision's R&D Cost model, the company spent an estimated $117m on the project between 2013 and 2018.
|Tenapanor sales by indication|
|Indication||Status||2024e sales ($m)||Note|
|Constipation-predominant irritable bowel syndrome||Filed||443||PDUFA date Sept 12|
|Hyperphosphataemia||Phase III||261||Amplify combo trial (NCT03824587) positive; Phreedom monotherapy trial (NCT03427125) data due Q4 2019|