Struggling Ardelyx gets rare trial win for tenapanor

This comes after a series of trial setbacks for the drug, notably with high adverse event rates in its previous test.

Ardelyx has hit its primary endpoint for its key asset tenapanor in a phase 3 hyperphosphatemia testa much needed positive after years of trial setbacks.

The late-stage placebo-controlled trial looked at tenapanor as a treatment for hyperphosphatemia (elevated level of phosphate in the blood) in patients with end-stage renal disease (ESRD) who are on dialysis.

The biotech released results showing its candidate met its primary endpoint within what it separated out as a “responder population” (this was 80 out of 164 patients) who had a mean reduction in serum phosphorus from baseline to the end of the 8-week treatment period of 2.56 mg/dL, with a reduction of up to 5.7 mg/dL.

In this group, the biotech said 33% of patients “had a reduction in serum phosphorus of greater than 3 mg/dL.” Overall, the data showed a statistically significant difference in serum phosphorus levels from the end of the 8-week treatment period to the end of the four-week randomized withdrawal period between the tenapanor-treated group and the placebo-treated group in the responder patient population, thus hitting its primary endpoint.

The topline safety results also found that just under 8% of patients stopped treatment due to GI side effects, but the biotech said it was “generally well-tolerated.” But 39% of patients in the 8-week period did suffer from diarrhea, although the biotech says it has a handle on this AE.

This will be a boon to the company, given that the drug previously met its main efficacy goal in a phase 2b trial on dialysis patients with hyperphosphatemia, but not without charting alarming rates of diarrhea compared with placebo. Another phase 3 test is planned later this year.

In a note to clients, analysts at Leerink said: “Although both measures were slightly lower than the 1.5mg/dl target, MEDACorp specialists viewed a reduction greater than 1mg/dL would have meaningful clinically utility.

“The rate of diarrhea was higher than on-market phosphate binders, but dropout rate due to GI effects including diarrhea was 8%, which is the more important measure, was low compared to 14% for Auryxia in clinical trials.”

Trial investigator Geoff Block, the director of clinical research at Colorado Kidney Care, said the results were “remarkable,” adding: “My patients are often required to take more than 19 pills per day, of which, nearly half are phosphate binders.

“The efficacy of tenapanor with only a few small pills, combined with its GI tolerability, has the potential to change the way in which we treat our patients in the future. I look forward to participating in the next phase 3 study and evaluating the full potential of this novel agent.”

But there is a tough history for the drug. In May 2015, the biotech posted data showing tenapanor flubbed the primary endpoint among 154 patients with stage 3 chronic kidney disease (CKD) and Type 2 diabetes, failing to significantly decrease the urinary albumin-creatinine ratio compared with placebo.

It did also hit the target in a phase 2b study of the drug for IBS, but investors were rattled by signs that the drug triggered serious diarrhea in many patients and triggered a rout, with shares plunging 30% in April 2015 when the data were posted.

AstraZeneca signed a $272 million partnership pact on the drug back in 2012, but a few years ago pulled out of the deal, giving rights back to Ardelyx after one too many setbacks (at a cost of $25 million to the biotech).

The company is also looking to finish off the T3MPO-1 and T3MPO-2 tenapanor phase 3 trials to treat IBS with constipation, as well as push forward with more testing for its hyperkalemia (a condition marked by high potassium levels in the blood) candidate RDX227675, an experimental potassium binder, which is set for a phase 3 registrational trial.

The biotech has a market cap of about $540 million and ended the day up just over 3% yesterday at $11.45 a share, before the trial update was released. It was up 6.5% first thing this morning, when the news hit the market.