Date: 2017-07-19
Type of information: Granting of a Market Authorisation in the EU
Product name: Veltassa™ - Patiromer FOS
Compound: patiromer sorbitex calcium
Therapeutic area: Cardiovascular diseases - Metabolic diseases - Rare diseases
Action mechanism:
- Veltassa® (RLY5016 for Oral Suspension - patiromer sorbitex calcium) is a high capacity non-absorbed, non-metal oral potassium binder being developed for the treatment of hyperkalemia. This non-absorbed, cation exchange polymer contains a calcium-sorbitol complex. Veltassa® increases faecal potassium excretion by binding potassium in the lumen of the gastrointestinal tract, resulting in a
reduction of serum potassium levels. The drug has been evaluated in chronic kidney disease patients with hyperkalemia, including a two part Phase 3 study, a 12-month Phase 2 trial and a 48-hour short-term Phase 1 onset-of-action study. In all of those studies, patiromer met its efficacy endpoints and the treatment was well tolerated.
Company: Relypsa (USA - CA) Vifor Fresenius Medical Care Renal Pharma France (France)
Disease: hyperkalemia
Latest news:
- • On May 18, 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion,
recommending the granting of a marketing authorisation for Veltassa®, intended for the treatment of hyperkalaemia. The drug will be available as a powder for oral suspension (8.4 g, 16.8 g and 25.2 g). The most common side effects are hypomagnesaemia, constipation, diarrhoea, abdominal pain and flatulence.
- • On November 27, 2016, Relypsa, a Vifor Pharma company, announced that the FDA has approved a supplemental New Drug Application (sNDA) with important updates to the label of Veltassa® (patiromer) for oral suspension. Veltassa’s label no longer includes a Boxed Warning regarding the separation of Veltassa® and other oral medications. The updated label recommends patients take Veltassa® at least 3 hours before or 3 hours after other oral medications.
- • On May 25, 2016, Relypsa announced that the company has submitted a sNDA to the FDA requesting label changes for Veltassa®(patiromer) for oral suspension based on results of
12 Phase 1 drug-drug interaction studies in healthy volunteers.
The drug-drug interaction program submitted as part of Veltassa®'s original New Drug Application (NDA) included in vitro drug-drug interaction tests (conducted in test tubes). In these initial in vitro tests, 28 drugs were tested. Fourteen showed binding with Veltassa® and 14 showed no binding.
Of the 14 drugs that did show binding in vitro, 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 Phase 1 studies showed that 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.
- • On April 25, 2016, Vifor Fresenius Medical Care
Renal Pharma (VFMCRP) and Relypsa announced that has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for Veltassa®
(patiromer) for oral suspension. VFMCRP is seeking approval of Veltassa® for the treatment of hyperkalemia through the EU centralized procedure. The European submission for Veltassa is supported by data from a comprehensive clinical development program that included:
- The pivotal Phase 3 OPAL-HK study, which was conducted under a FDA Special Protocol Assessment and evaluated
Veltassa in hyperkalemic patients with chronic kidney disease who were taking renin angiotensin aldosterone
system (RAAS) inhibitors;
- The Phase 2 AMETHYST-DN trial, which evaluated the use of Veltassa over 52 weeks in hyperkalemic patients with
CKD and type 2 diabetes who were taking RAAS inhibitors;
? An open-label, uncontrolled, Phase 1 study that evaluated the onset-of-action of Veltassa in hyperkalemic chronic kidney disease patients. The European submission will undergo a formal acceptance and validation phase by the EMA during May 2016.
- • On December 21, 2015, Relypsa announced that Veltassa™ (patiromer) for oral suspension is now available for prescription to patients with hyperkalemia in the United States. Veltassa was approved by the FDA on October 21, 2015 (See below). It is the first new medicine for the treatment of hyperkalemia, or elevated blood potassium levels, in more than 50 years.
- • On October 21, 2015, the FDA approved Veltassa™ (patiromer for oral suspension) to treat hyperkalemia. Potassium is needed for cells to function properly. The kidneys remove potassium from the blood to maintain a proper balance of potassium in the body. But when the kidneys are not able to remove enough potassium from the blood, the level of potassium can get too high. Hyperkalemia typically occurs in patients with acute or chronic kidney disease or heart failure, particularly in those who are taking drugs that inhibit the renin-angiotensin-aldosterone system, which regulates blood pressure and fluid balance in the body. Veltassa™, a powdered medication that patients mix with water and take by mouth, works by binding potassium in the gastrointestinal tract, decreasing its absorption. In clinical trials, Veltassa™ was effective in lowering potassium levels in hyperkalemic participants with chronic kidney disease on at least one drug that inhibited the renin-angiotensin-aldosterone system.
- In clinical trials, the most common adverse reactions reported by participants taking Veltassa were constipation, decreased magnesium levels in the blood (hypomagnesemia), diarrhea, nausea, abdominal discomfort, and flatulence. Veltassa should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.
- Veltassa™ has a boxed warning because it binds many 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. The drug must be dispensed with a patient Medication Guide that describes important information about its uses and risks.
- The FDA approval of Veltassa™ was based on a clinical development program that studied patients who are representative of people who typically experience high blood potassium levels, including people who had CKD, heart failure, diabetes and hypertension. The pivotal Phase 3 OPAL-HK study showed Veltassa™ significantly decreased potassium levels in hyperkalemic CKD patients taking RAAS inhibitors (mean decrease of -1.01 ± 0.03 mEq/L from baseline; p<0.001). At four weeks, 76 percent of patients had potassium levels in the target range (3.8 to <5.1 mEq/L). During the second part of the trial, patients taking Veltassa had no change in median potassium from baseline (0.00 mEq/L), whereas potassium levels significantly increased in the placebo group (0.72 mEq/L; p<0.001).
- The Phase 2 AMETHYST-DN trial evaluated use of Veltassa™ over 52 weeks in hyperkalemic patients with CKD and type 2 diabetes who were taking RAAS inhibitors. Throughout the year-long study, the majority of patients had potassium levels in the target range (3.8-5.0 mEq/L).
- An open-label, uncontrolled, Phase 1 study evaluated Veltassa™'s onset-of-action in 25 hyperkalemic CKD patients. The mean baseline blood potassium level was 5.9 mEq/L. A statistically significant reduction in blood potassium levels was first observed at 7 hours after the first dose. Potassium levels continued to decline during the 48-hour treatment period of the study (-0.8 mEq/L at 48 hours after the first dose).
- In the clinical trials, most adverse reactions were mild to moderate. The most common adverse reactions in all trials included constipation (7.2 percent: 5.4 percent mild and 1.8 percent moderate), hypomagnesemia (low magnesium levels; 5.3 percent), diarrhea (4.8 percent), nausea (2.3 percent), abdominal discomfort (2.0 percent) and flatulence (2.0 percent).
- • On October 22, 2014, Relypsa announced that the company has submitted a New Drug Application (NDA) to the FDA seeking approval to market Patiromer for Oral Suspension (Patiromer FOS) for the treatment of hyperkalemia, a serious condition defined as abnormally elevated levels of potassium in the blood.
The NDA is supported by eight clinical trials, including a Phase 3 program that was conducted under a Special Protocol Assessment as well as a Phase 2 trial that evaluated Patiromer FOS in patients for up to one year.
Patiromer has been evaluated in CKD patients with hyperkalemia, including a two part Phase 3 program, a 12-month Phase 2 trial and a 48-hour Phase 1 onset-of-action trial. In all of those trials , Patiromer FOS met its efficacy endpoints and the treatment was well tolerated. The pivotal clinical trial for Patiromer FOS was conducted under a Special Protocol Assessment with the FDA.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE: 2016-04-25
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2015-10-21
UE authorization: 2017-07-19
Favourable opinion UE: 2017-05-18
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
