Ardelyx has been on a years-long roller coaster ride with their drug tenapanor. But early this morning the biotech $ARDX pulled the wraps off a Phase III study that they say met the primary endpoint for treating hyperphosphatemia in patients with end-stage renal disease who were on dialysis. And they add that they were able to do it with an acceptable level of problems with diarrhea — an issue that earlier raised an alarming warning flag for investors.
“This is going to be something that will change outcomes for patients on dialysis,” says CEO Mike Raab, who now plans to sit down with the team and regulators and finish up a new Phase III study design that he believes will open the door to the market. The next late-stage study, he adds, will start in a few months.
Investors, though, weren’t quick to back the company’s position. Their stock was up only 2% in pre-market trading, indicating a high level of skepticism for their prospects.
The way this study was designed, says development chief David Rosenbaum, patients were taken off their phosphate binders (like Renvela, a standard of care for treating elevated levels of phosphate) and their serum phosphorus levels were checked.The subjects who responded with a minimum serum phosphorus increase of 1.5 mg/dL were then given the drug during an 8-week period when the therapy could be titrated. After 8 weeks they were then randomized to a placebo and investigators looked for a change in serum phosphate levels after 4 weeks.
According to Ardelyx, that responder population, 49% of the total recruited, demonstrated a mean response of -1.01 mg/dL on drug, a statistically significant response. And, they added:
The responder population (n=80 out of 164) had a mean reduction in serum phosphorus from baseline to the end of the eight-week treatment period of 2.56 mg/dL, with a range of reduction from 1.2 mg/dL to 5.7 mg/dL. Notably, in this group, 33 percent of patients had a reduction in serum phosphorus of greater than 3 mg/dL.
There was a 7.8% discontinuation rate in the study due to diarrhea (and a 39% diarrhea rate in the first 8 weeks) which Rosenbaum says was distinctly smaller than the alarming spike that was point out in Phase IIb. But by titrating the drug during the first stage of treatment, he added, they were able to better control diarrhea.
“Although (outcome) measures were slightly lower than the 1.5mg/dl target, MEDACorp specialists viewed a reduction greater than 1mg/dL would have meaningful clinically utility,” noted Leerink’s Jason Gerberry. “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.”
AstraZeneca had been in charge of the Phase IIb for this drug in ESRD but pulled out of their pact after the dustup over the safety data.
“People were concerned about the 30 mg fixed and that was the press release that came out,” Raab tells me. “AstraZeneca chose not to speak to key opinion leaders.” But if they had, he added, they would likely have had a different response than just pulling out.
Ardelyx has a key opinion leader working with their team, and he touted the advantage a drug like tenapanor can have for patients in a prepared statement.
“The reduction in serum phosphorus in many patients treated with tenapanor is remarkable. These data validate tenapanor’s unique mechanism of action and its potential to be the first non-phosphate binder treatment for this difficult-to-manage disorder,” said Geoff Block MD, director, clinical research at Colorado Kidney Care, and a Phase III investigator. “My patients are often required to take as many as 19 pills per day, of which phosphate binders are nearly half. The efficacy of tenapanor with only a few small pills, combined with its GI tolerability, may 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.”
We won’t know how payers view it until it gets through another late-stage study and passes muster with the FDA, a high wire act by any measure.
But Raab says he’s glad that AstraZeneca is gone.
“The beauty of what we have is that we own this drug outright,” he says, with a clear shot at handling the US market alone while partners can be lined up for ex-US markets.
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