- Relypsa reports results from Phase 1 in vivo studies in healthy volunteers evaluating potential drug-drug interactions between Veltassa and 12 drugs administered either at the same time or three hours apart
- The 12 drugs were selected based on results of previously announced in vitro tests, in which Veltassa had demonstrated binding with 14 of 28 drugs tested; 12 of these 14 were considered relevant for further testing to assess whether the in vitro results translated into an effect in people
- Results of the Phase 1 studies showed nine of the 12 drugs tested showed no clinically meaningful reduction in absorption when administered at the same time as Veltassa
- No reduction in absorption was observed for any of the 12 drugs tested with a three-hour dosing separation from Veltassa
- Relypsa management will discuss the results further on a conference call/webcast this afternoon, Monday, January 25, 2016, at 5:30 p.m. ET/2:30 p.m. PT
REDWOOD CITY, Calif., Jan. 25, 2016 (GLOBE NEWSWIRE) -- Relypsa, Inc. (NASDAQ:RLYP), a biopharmaceutical company, today announced results from 12 Phase 1 studies in healthy volunteers evaluating potential drug-drug interactions between Veltassa® (patiromer) for oral suspension and 12 drugs that had previously demonstrated binding in in vitro tests. When Veltassa was administered at the same time as the drugs being tested, there was no clinically meaningful reduction in absorption for nine of the 12 drugs. Three drugs showed reduced absorption when they were co-administered with Veltassa, however, when dosing of Veltassa and these drugs was separated by three hours, no reduction in absorption was observed.
“The results from these studies are encouraging as, of the 12 drugs that had previously shown in vitro binding to Veltassa, nine showed no clinically meaningful reduction in absorption when co-administered with Veltassa in people,” said Lance Berman, M.D., chief medical officer of Relypsa. “In addition, when dosing was separated by three hours, there was no impact to absorption of the three drugs that had demonstrated reduced absorption when they were given with Veltassa. We look forward to discussing these data with the FDA and determining next steps.”
Summary of Veltassa Drug-Drug Interaction Program and Results
Veltassa was approved by the U.S. Food and Drug Administration (FDA) on October 21, 2015, for the treatment of hyperkalemia, becoming the first new medicine in more than 50 years for people with elevated blood potassium levels.
The drug-drug interaction program submitted as part of Veltassa’s New Drug Application (NDA) included in vitro drug-drug interaction tests (conducted in test tubes).
As previously announced, in these initial in vitro tests, 14 of the 28 drugs showed no binding with Veltassa, including:
- Antihypertensive medicines (renin angiotensin aldosterone system, or RAAS, inhibitors) – lisinopril, spironolactone, valsartan
- Cholesterol-lowering medicine – atorvastatin
- Anticoagulant and antiplatelet medicines – apixaban, aspirin, rivaroxaban
- Cardiac glycoside – digoxin
- Antidiabetic medicine – glipizide
- Antigout medicine – allopurinol
- Antibiotics – amoxicillin, cephalexin
- Antiepileptic – phenytoin
- Vitamin – riboflavin
Fourteen drugs did show binding in vitro and, of these, 12 were selected for further testing in healthy volunteer studies to assess whether the results seen in vitro translated into an effect in people. These randomized, open-label studies were initiated in September 2015 and used a three-way cross-over design. They evaluated the absorption of these 12 drugs when either co-administered with Veltassa or when administered three hours apart from Veltassa. In each study, participants received:
- The test drug alone;
- Veltassa and the test drug administered at the same time; or
- Veltassa administered three hours after the test drug.
For each drug tested, the studies evaluated the concentration in the blood over time (area under the curve or AUC) and the peak blood concentration (Cmax).
Results of Phase 1 In Vivo Studies
|Drugs||Veltassa and test drug |
administered at the same time
|Veltassa administered three hours |
after test drug
|Lithium (psychiatric medicine)||-- No clinically meaningful reduction in absorption (AUC) |
-- No impact on peak concentration (Cmax)
|-- No impact on absorption (AUC) |
-- No impact on peak concentration (Cmax)
|Amlodipine (antihypertensive)||-- No clinically meaningful reduction in absorption (AUC) |
-- Some reduction in peak concentration (Cmax)
|Ciprofloxacin (antibiotic)||-- Reduced absorption (AUC) |
-- Reduced peak concentration (Cmax)
|Levothyroxine (thyroid hormone replacement)|
|Quinidine (antiarrhythmic)||-- Not tested in humans (quinidine rarely used; thiamine commonly present in food)|
Conference Call Monday, January 25, 2016, at 5:30 p.m. ET (2:30 p.m. PT)
The Relypsa management team will host a conference call and webcast Monday, January 25, 2016, to further discuss the results of these studies. The conference call may be accessed by phone by calling (866) 410-4428 (domestic) or (704) 908-0287 (international), conference code 38500171. To access the slides and live audio webcast, visit the investor relations section of the Relypsa website at http://investor.relypsa.com. The webcast will be archived for 30 days following the call.
Veltassa is a potassium binder approved for the treatment of hyperkalemia. Veltassa should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.
Made in powder form consisting of smooth, spherical beads, this new medicine is mixed with water (90 milliliters or three ounces) and taken once-a-day with food. Veltassa is not absorbed and acts within the gastrointestinal tract. It binds to potassium in exchange for calcium, primarily in the colon. The potassium is then excreted from the body through the normal excretion process.
IMPORTANT SAFETY INFORMATION
The Prescribing Information for Veltassa includes a Boxed Warning that Veltassa binds to many other orally administered medications, which could decrease their absorption and reduce their effectiveness. Other oral medications should be administered at least six hours before or six hours after Veltassa. Doctors should choose Veltassa or the other oral medication if adequate dosing separation is not possible.
Veltassa is contraindicated in patients with a history of a hypersensitivity reaction to Veltassa or any of its components.
Worsening of Gastrointestinal Motility
Use of Veltassa should be avoided in patients with severe constipation, bowel obstruction or impaction, including abnormal post-operative bowel motility disorders, because Veltassa may be ineffective and may worsen gastrointestinal conditions. Patients with a history of bowel obstruction or major gastrointestinal surgery, severe gastrointestinal disorders, or swallowing disorders were not included in clinical studies.
Veltassa binds to magnesium in the colon, which can lead to hypomagnesemia. In clinical studies, hypomagnesemia was reported as an adverse reaction in 5.3 percent of patients treated with Veltassa. Approximately 9 percent of patients in clinical trials developed hypomagnesemia with a serum magnesium value <1.4 mg/dL. Doctors should monitor serum magnesium and consider magnesium supplementation in patients who develop low serum magnesium levels.
The most common adverse reactions (incidence ≥2 percent) were constipation, hypomagnesemia, diarrhea, nausea, abdominal discomfort and flatulence. Mild to moderate hypersensitivity reactions were reported in 0.3 percent of patients treated with Veltassa and included edema of the lips.
For additional Important Safety Information and Veltassa’s full Prescribing Information, please visit www.relypsa.com/veltassa/prescribing-information.
About Relypsa, Inc.
Relypsa, Inc. is a biopharmaceutical company focused on the discovery, development and commercialization of polymeric medicines for patients with conditions that are often overlooked and undertreated and can be addressed in the gastrointestinal tract. The Company’s first medicine, Veltassa® (patiromer) for oral suspension, was developed based on Relypsa’s rich legacy in polymer science. Veltassa is approved in the United States for the treatment of hyperkalemia. Veltassa has intellectual property protection until 2030 in the United States and 2029 in the European Union. More information is available at www.relypsa.com.
To the extent that statements contained in this press release are not descriptions of historical facts regarding Relypsa, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including statements regarding the potential significance of the drug-drug interaction results and the plans to discuss the results with the FDA and determine next steps. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development program, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the clinical drug development and commercialization process, including regulatory requirements, the timing of Relypsa's regulatory filings, Relypsa's substantial dependence on Veltassa, Relypsa's commercialization plans and efforts and other matters that could affect the availability or commercial potential of Veltassa. Relypsa undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of Relypsa in general, see Relypsa's current and future reports filed with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2014, and its Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2015.
Vice President, Corporate Communications