ZS Pharma Passes Key Test With Drug for Hyperkalemia

[Corrected 11/22/13, 1:55 pm. See below.] Chronic kidney disease affects 26 million patients in the U.S., and they spend a lot of money trying to manage the condition. Fort Worth, TX-based ZS Pharma is betting that it might have one more new option to help many of these patients.

ZS Pharma reported earlier this month that preliminary data from its Phase III trial 0f 753 patients showed its experimental drug was able to reduce excess amounts of potassium in the blood of patients with hyperkalemia. The finding–if confirmed in another big study—could be medically important. That’s because people with failing kidneys are often left with too much potassium in the blood, which can lead to potentially deadly arrythmias—an irregular heart rhythm.

“The thing we’re most excited about is that the drug is shown to be active and extremely safe,” says Robert Alexander, ZS’s executive chairman. “As potent as this drug is, we are thrilled to learn that it can be well tolerated.”

ZS Pharma made its announcement about ZS-9—a white odorless, tasteless powder that can be combined with water to make a suspension—earlier this month at Kidney Week, the American Society of Nephrology’s annual meeting. The study randomly assigned patients to get one of four doses—1.25 grams, 2.5 grams, 5 grams, and 10 grams—or a placebo, three times a day for two days. The company reported that the drug led to declines in potassium in 48 hours and that the drug appeared to be safe over the two-day period. [An earlier version of this story misstated the number of days that patients in the study were treated in the acute phase of the trial. We regret the error.]

ZS Pharma did not disclose the baseline levels of potassium of patients who entered the study, so the preliminary results do not show if the patients’ potassium levels were brought down to a normal range. The ZS-9 trial enrolled patients with mild to moderate hyperkalemia.

A spokeswoman for the company would only say that the full report would be available “in the coming months.”

“We wanted to really understand how the drug works across a range of doses,” Alexander says. “The main reason for hyperkalemia is high potassium, but there is a range of hyperkalemia. It’s’ a matter of making sure you get the right dose for the right patient.”

What would be key to know is how the drug fared against sodium polystyrene sulfonate (Kayexalate), which has been the mainstay in care for patients with hyperkalemia since the 1960s. Alexander says ZS Pharma did not conduct trials comparing ZS-9 with Kayexalate because the drug was approved under the FDA’s DESI program, which classified all pre-1962 drugs that were already on the market as either effective, ineffective, or needing further study. So, he added, Kayexalate, did not go through clinical trials and produce data that could be compared with drugs such as ZS-9.

Alexander says the difference between the two is that the existing product is an organic polymer that binds calcium, potassium, and sodium, while ZS-9 is an inorganic crystal that has the ability to select only potassium for removal. A big issue with Kayexalate is that most patients experience diarrhea. In the Phase III trial of the ZS Pharma drug, about 3.5 percent of patients experienced gastrointestinal distress, compared with 5.1 percent who reported that effect while on the placebo, Alexander says.

“The highest dose was the best tolerated in all our dosing groups,” he added.

ZS plans to do another study that follows patients for 28 days, with a similar design to the recently completed 12-day study. Alexander declined to specify the number of patients or the dosage amounts in the next study. Upon successful completion, he added that the company plans to file a new drug application with the Food and Drug Administration in the fourth quarter of next year.

ZS is not the only life sciences startup looking for a better way to treat hyperkalemia. Redwood City, CA-based Relypsa (NASDAQ: RLYP) went public earlier this month, and has said it plans to file a new drug application to the FDA before the end of 2014.

ZS was founded in 2008 by Alvaro Guillem, who is now the startup’s CEO, Jeffrey Keyser, the current chief operating officer, and Stephen Ash, a nephrologist at Indiana University Health. Alexander first met up with them in 2010 when he was at Alta Partners but didn’t decide to invest in their work until 2012.

“It was, frankly, shocking how quickly they went from animal data to the human proof of concept stage,” he says. “Their Phase II data looked fantastic.”

That mid-stage study examined the safety and efficacy of three doses of the drug, at 0.3 grams, 3 grams, and 10 grams.

So far, ZS Pharma has raised about $56 million, $10 million of which came from the Texas Emerging Technologies Fund and Series B round led by Devon Park BioVentures. Its most sizable funding came in last October, a Series C round led by Devon, Alta Partners, RiverVest, Salem Partners, and 3×5 Special Opportunity Partners.

Alexander left Alta to join ZS in March. He says the startup will likely go out to raise an additional round of money next year but declined to provide specifics. He says the plan is to develop and market the drug in the United States alone, without the help of a partner. “Assuming we are a standalone company, sometime in the future, we would look to partner to launch the product ex-North America,” he added.

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