On Oct. 21, the U.S. Food and Drug Administration approved Relypsa, Inc.’s Veltassa (patiromer for oral suspension) to treat hyperkalemia. Veltassa is the first new medicine to treat hyperkalemia in more than 50 years.
I spoke with Dr. Lance Berman, chief medical officer for Relypsa, about the new drug.
"What makes me happy as a physician is that the hard work and research has paid off on a very important label," Berman said. "The approval shows us that the drug has excellent efficacy over the long term, is well tolerated over the long term, it's easily administered to patients with a small amount of water, and it should be able to be used in multiple patient types because of its broad indication. …"We're very happy with the label, I think it's going to give physicians exactly what they haven't had for 50 years, in terms of a new treatment option for hyperkalemia."
Hyperkalemia, and the need for a new treatment
Managing hyperkalemia is a challenge because it is a recurrent issue, Berman said. "The underlying cause is persistent and often progressive, and the complication very seldom goes away."
Physicians have historically had a few choices for managing high potassium, all of which, Berman said, have been dissatisfying for various reasons.
- Begin by teaching patients to stick to a low potassium diet. "The diet is difficult to stick to because potassium is ubiquitous in many fresh fruits and vegetables, as well as dairy products," Berman said.
- If diet alone cannot control potassium, increase doses of diuretic medications, which lose their effectiveness as patients lose kidney function.
- Most physicians end up having to stop the use of Renin Angiotensin System (RAS) inhibitor medications, which are important medications for kidney disease patients because they can lower blood pressure, reduce proteinuria, slow the progression of kidney disease, and reduce cardiovascular disease risk. According to Berman, stopping RAS medications has become the most common intervention option available to physicians.
- The last resort is normally sodium polystyrene sulfonate (Kayexalate), which was approved in 1958, before drug manufacturers were required to prove the effectiveness and safety of their drugs through randomized control trials. This drug was developed to bind potassium to the GI tract. Kayexalate is often poorly tolerated by patients because it tastes terrible and is severely constipating. It also has rare, but very severe complications. And it works by exchanging sodium in order to bind potassium, which is not good for CKD and heart failure patients that cannot tolerate small increases in sodium and fluid load, Berman said.
Historically, there was "not much physicians can do on a daily basis to reduce potassium levels," Berman said.
Veltassa indications and clinical practice
The drug was approved as a treatment drug, to lower and maintain control in patients with high potassium. It is not approved as a preventative drug, and is not intended for use as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.
Berman estimates there are about 3.5 million pre-dialysis CKD and dialysis patients, many with heart failure, with high potassium. Nephrologists and cardiologists tend to monitor potassium levels that go above 5 mEq/L, and take action at 5.5 mEq/L or higher. He said as physicians start to feel comfortable with the new drug and its effects, he predicts they will begin using Veltassa as potassium levels reach 5 mEq/L, or 5.5 mEq/L.
Veltassa's boxed warning and its usefulness for kidney disease patients
Veltassa has a boxed warning because it binds to other orally administered drugs, which could decrease their absorption and reduce their effects. The warning recommends taking it and any other orally administered medication at least six hours apart.
"If you look at most boxed warnings, they in general are related to a known specific side effect. That's not the case with the boxed warning on our drug … There is a potential for many patients to be suitable for this drug, and because it has the potential to be used in so many patients, the FDA wanted to remind physicians to separate six hours between other medications," Berman said.
Based on clinical trial data and market research data, Berman said they found that the majority of patients who can be treated with Veltassa are on once or twice daily medications, and "we can incorporate Veltassa into the daily regimen." He said he thinks this is "workable in the majority of patients."
Veltassa's use with phosphate binders
Berman said he doesn't know if Veltassa would work with phosphate binders.
"The reason why we never studied it is because in our clinical program, all of the trials except one enrolled patients before they needed dialysis, because we believe the biggest unmet need is in pre-dialysis patients, because dialysis itself helps reduce the potassium level. And as you know phosphate binders are not indicated in that patient population, although there is some use. We also excluded phosphate binders from our trials because they are known to have a fairly high GI complication rate. And we didn't want to allow the use of those drugs in our studies because it would have been very difficult to determine whether the GI problems were related to Veltassa or the phosphate binder. "
Study of Veltassa in dialysis patients
The very first patient trial was a proof of concept study in dialysis patients. "It was a very small study of six patients that proved the drug worked by binding to potassium in the GI tract, and then excreted through feces," Berman said. "The product has a very broad indication. There's no limits to the cause of hyperkalemia, and no restriction to the patient type. It can be used in any patient with hyperkalemia with any cause. Most often these are patients with CKD, but it can also be patients with severe burns or crush injuries, or transplant patients on immunosuppressives, or hemodialysis patients with high potassium levels."
Veltassa compared to Kayexelate
"Veltassa was made to be very different structurally than Kayexelate. Kayexelate is made as a block, and it is ground down into a powder, which results in very irregular shaped crystals," Berman said. "And it swells a lot when you mix it with water, which gives it a very thick muddy consistency, and it doesn't flow very nicely through the GI system. Veltassa was developed with a process called suspension polymerizations, which allows us to make the powder with very small uniform beads, and these beads are spherical and don't swell very much when mixed with water, which gives it very good flow properties. So you only need three ounces of water to mix it with. Which is great for fluid restricted patients. So this is why we didn't see very high constipation rates."
"When we conducted the clinical trial program to get the drug to the FDA, we agreed we didn't need to do any trials comparing Veltassa to Kayexelate because patients don't tolerate Kayexelate for very long, " Berman said. "It is very difficult to dose patients with this drug for longer than a few days. And since we were looking at long term studies, four weeks, 12 weeks, and then one year, there was no way patients would stay on Kayexelate long enough to conduct those trials. "
Relypsa said that they expect to make Veltassa available to patients in the United States by the first week of January 2016. -by Rebecca Zumoff