Ardelyx Inc (NASDAQ:ARDX) just put out data from a phase III study in patients with end stage renal disease, and the company is running up on the back of the news. There are a few noteworthy elements of this study (and the release) that we see as pertinent to forming a longer term bias on the stock, so with this in mind, and in the wake of the trial data drop, here’s what we see as important going forward.
So, first up, a quick introduction to Ardelyx.
The company is a development stage biotechnology company that is working to bring treatments to market in the spaces of cardiorenal and gastrointestinal (GI) diseases. To get a little more specific on this, it’s trying to improve on the current standard of care treatments in this space by using the gut as a gateway to delivering active ingredients (we’ll look at this in a bit more detail shortly).
Its lead development asset is called Tenapanor, and the trial in focus here was investigating the efficacy of the drug as a therapy for a condition called hyperphosphatemia, which is an electrolyte disturbance in which there is an abnormally elevated level of phosphate in the blood. As mentioned above, it’s specifically looking at this condition in patients with end stage renal disease, with hyperphosphatemia being a common secondary-onset condition associated with kidney dysfunction. Kidneys are able to remove excess phosphate remove the blood, and serve as a sort of backup removal system as and when levels get too high in healthy patients. In patients that have renal disease, of course, the kidneys don’t work properly, and the excess phosphate doesn’t get removed.
Tenapanor has a pretty interesting MOA. It blocks what’s called the NHE3 sodium transporter in the GI tract, and this results in the reduced absorption of dietary sodium (which in turn, results in an increased number of protons within the cells). The increase in protons causes a selective reduction in phosphate uptake by tightening junctions or pores that regulate phosphate absorption in the GI tract. Reduced phosphate uptake translates to a reduced blood serum phosphate level, and therein lies the clinical benefit.
That’s the theory, at least, and it’s this theory that the company sought to prove with its phase III study in the indication.
And prove it, it has.
In a responder population (80 patients out of 164) there was mean reduction in serum phosphorus from baseline to the end of the eight-week treatment period of 2.56 mg/dL, with a reduction of up to 5.7 mg/dL. Additionally, and of worthy note, in this group, one third of patients had a reduction in serum phosphorus of greater than 3 mg/dL.
For those not familiar with standard of care improvements in this indication, these numbers are exemplary. But that’s not all. One of the main concerns surrounding this drug (a concern that arose as part of previous studies) was a side effect of diarrhea. In previous studies, a high rate of severe diarrhea caused a large portion of study participants to discontinue. In this case, however, while 39% of patients reported diarrhea as a primary symptom, only 7.8% discontinued the study as a direct result of the side effect. In previous trials, this number was low double digits – to the degree that we saw it as a major red flag. Basically, with the previous discontinuation rates, the FDA probably wouldn’t have approved the drug. With these reduced rates, however, the side effect will likely not be prohibitory to an FDA green light.
So what’s next?
The company wants to conduct one more phase III study and use this study to build on its current data bank. This follow up will include a 26-week open-label treatment period, with a randomized withdrawal period, followed by an additional 26-week long-term safety extension, and – as per the latest communication – should kick off at some point during the middle of this year.
As such, that’s our next focal point for Ardelyx. When the company kicks off the study, we expect some increased speculative volume, and we should see the company gain strength into the latter half of 2017 as a result.