One of the biggest midweek movers in the biotechnology space this week is Ardelyx, Inc. (NASDAQ:ARDX). The company just put out data from one of its lead investigations into a development asset called tenapanor, which it is trying to get approved for the treatment of irritable bowel syndrome with constipation (IBS-C).
The study was a phase 3 study called T3MPO-2 and was a follow-up to an initial phase 3 study (this is one of those indications that generally needs two studies carried out before submission to the FDA) that completed back in May and did so successfully. If Ardelyx could replicate the data picked up from the first study and reinforce the suggestion of efficacy (as well as safety, of course) then the company would have a strong chance of picking up an FDA approval on submission.
So what did the data tell us?
Well, in short, things look pretty good.
The primary endpoint for the study was a combined responder rate that included at least a 30% reduction in abdominal pain and an increase of one or more complete spontaneous bowel movements (CSBM) in the same week for at least six of the 12 weeks of the treatment period.
As per the data, 36.5% of patients met these criteria in the active arm, while only 23.7% of patients did so on the placebo arm, with a p-value of less than 0.001, meaning the results are strongly statistically significant.
A range of secondary endpoints was also investigated, measuring things like quality of life and other pain type scales and all of the secondary endpoints were hit, with the active outperforming the placebo with a high degree of statistical significance.
From a safety perspective, the key metric was the rate of diarrhea among active arm patients versus that of control patients. In the initial study, the one that completed in May, rates of diarrhea were 14.6% in active arm vs 1.7% for placebo. The data from the latest study came in as pretty similar, with the numbers at 16.0% vs. 3.7%.
While this metric is something of a concern, it’s not really a dramatic setback in a study like this. Patients go into the trial knowing that diarrhea is a potential adverse event, as compared to the symptoms of the condition itself (as well as when considered against the adverse event of the currently available treatment) diarrhea, assuming it is not too bad, isn’t that big of a deal.
So what’s next?
Well, now it’s all about collecting this data together and putting it into a new drug application (NDA) that Ardelyx can submit to the agency in the US in an attempt to pick up regulatory approval. Management has given us some degree of insight into when this is likely to take place, suggesting that NDA submission should come during the second half of 2018. That’s quite a while away, but we’ve got to bear in mind that there are two large-scale trials supporting this application and it’s better for the company to get together exactly what it needs and ensure the best chance of a first-time approval before submitting. It’s far cheaper to spend a little more time on a submission first time around than it is to pick up a complete response letter (CRL) on an initial submission, take a hit to share price on the back of the CRL and then have to spend time rectifying any FDA concerns ahead of a secondary submission.
What are the chances of approval?
As mentioned above, the efficacy data seems strong here. The company has been able to show in two pretty large scale studies that its drug can work in a patient population for which there aren’t too many desirable options right now and that it can do so with not too high a rate of severe adverse events.
And what are the implications of an approval for Ardelyx and its shareholders?
Analysts put peak sales estimates of the drug at around $500 million. When considered against the company’s current market capitalization, which comes in at just $256 million, it’s clear that there is plenty of upside potential on current share price if the FDA green lights this asset, come decision day.