California biotech Ardelyx has a second positive trial for its lead drug tenapanor in chronic kidney disease (CKD), as it waits for an FDA verdict on the use of the drug in irritable bowel syndrome.
The latest AMPLIFY trial – involving CKD patients on dialysis with elevated blood phosphate levels in the blood despite phosphate binder therapy – showed that tenapanor was able to reduce levels significantly compared to placebo.
Twice as many patients on tenapanor achieved the established treatment goal of reducing serum phosphate to less than 5.5 mg/dL compared to placebo (49.1% versus 23.5%) after four weeks, the study’s primary endpoint, and it also hit all secondary objectives.
High phosphate levels – hyperphosphatemia – is a common complication of CKD and particularly affects patients on dialysis and if severe can cause bone and muscle problems as well as increase the risk of heart attacks and strokes.
Tenapanor also achieved a 22%-24% reduction in levels of FGF23, a biomarker linked to an elevated risk of cardiovascular complications in CKD patients, compared to control.
Shares in Ardelyx rocketed 72% on the back of the new study on the prospect of a second indication for tenapanor to follow constipation associated with IBS, which is under review by the FDA with a decision due in the next couple of weeks.
The first-in-class drug – which was licensed to AstraZeneca at one point before Ardelyx brought it back in house to speed up development – is a small molecule that is dosed orally twice a day.
It acts locally in the gastrointestinal tract to inhibit the sodium transporter NHE3 and reduce sodium and phosphorus uptake from the diet. That mechanism means it was associated with a higher rate of diarrhoea than placebo, affecting around a third of patients on the drug.
An earlier phase 3 study showed that tenapanor was effective as a monotherapy in CKD patients on dialysis, which also met its main objective with 50% of patients experiencing a mean serum phosphate reduction of 2.56 mg/dL.
A second monotherapy phase 3 trial, called PHREEDOM, is due to report data before the end of the year and if positive Ardelyx says it will file for both monotherapy and combination use of the drug for the treatment of hyperphosphatemia.
Analysts at Jefferies have previously said that tenapanor addresses a major unmet medical need by offering a much lower pill burden than conventional phosphate binders, while Piper Jaffray has suggested the drug has $1bn sales potential that isn’t recognised by Wall Street.
In a recent research note Piper’s Christopher Raymond said nephrologists seem to be “fully aware of this drug’s potential with swift and dramatic uptake projected if approved”, and he thinks tenapanor is “poised to be one of biotech’s great product launches of 2021”.