Date: 2016-02-19
Type of information: Granting of a Market Authorisation in the EU
Product name: Zurampic®
Compound: lesinurad
Therapeutic area: Metabolic diseases
Action mechanism: uric acid reabsorption inhibitor. Lesinurad is a selective uric acid reabsorption inhibitor (SURI) that inhibits the URAT1 transporter and is being studied as an investigational agent for the treatment of gout. URAT1 is responsible for the majority of the reabsorption of filtered uric acid from the renal tubular lumen. By inhibiting URAT1, lesinurad increases uric acid excretion and thereby lowers sUA. Lesinurad also inhibits OAT4, a uric acid transporter involved in diuretic-induced hyperuricaemia.
Lesinurad has been developed by Ardea Biosciences, a member of the AstraZeneca Group.
Company: AstraZeneca (UK)
Disease: hyperuricaemia associated with gout
Latest news:
- • On February 19, 2016, AstraZeneca announced that the European Commission has granted marketing authorisation for Zurampic® (lesinurad) 200mg in combination with a xanthine oxidase inhibitor (XOI) for the adjunctive treatment of hyperuricemia in adult gout patients (with or without tophi) who have not achieved target serum uric acid (sUA) levels with an adequate dose of an XOI alone. In combination with the current standard of care, XOIs allopurinol or febuxostat, Zurampic® provides a dual mechanism of action to increase excretion and decrease production of uric acid, enabling more patients with inadequately controlled gout to achieve target treatment goals. As part of the European Union (EU) approval, AstraZeneca will conduct a Non-Interventional Post-Authorisation Safety Study (PASS) to investigate the cardiovascular safety profile (mainly in patients with history of cardiovascular disorder) exposed to Zurampic. In addition to the PASS, AstraZeneca also agreed to conduct an EU renal study to assess efficacy and safety in patients with creatinine clearance of 30-45mL/min.
- • On December 22, 2015, the FDA approved Zurampic® (lesinurad) to treat high levels of uric acid in the blood (hyperuricemia) associated with gout, when used in combination with a xanthine oxidase inhibitor (XOI), a type of drug approved to reduce the production of uric acid in the body. Zurampic® works by helping the kidney excrete uric acid. It does this by inhibiting the function of transporter proteins involved in uric acid reabsorption in the kidney.
The safety and efficacy for Zurampic® were evaluated in three randomized, placebo-controlled studies in combination with a XOI involving 1,537 participants for up to 12 months. Participants treated with Zurampic® in combination with a XOI experienced reduced serum uric acid levels compared to placebo.
The most common adverse reactions in clinical trials were headache, influenza, increased blood creatinine, and gastroesophageal reflux disease.
Zurampic® has a boxed warning that provides important safety information for health care professionals, including the risk for acute kidney (renal) failure, which is more common when used without an XOI and with higher than approved doses of Zurampic®. The FDA is also requiring a postmarketing study to further evaluate the renal and cardiovascular safety of Zurampic®.
- • On 17 December 2015, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Zurampic®, as adjunctive treatment of hyperuricaemia in combination with a xanthine oxidase inhibitor in adults with gout. Zurampic® will be available as 200 mg film-coated tablets. The benefit of Zurampic® is its ability to increase uric acid excretion and thereby lower serum uric acid levels. The most common side effects are headache, influenza, increased blood creatinine and gastrooesophageal reflux.
AstraZeneca anticipates a final decision by the EC in the first quarter of 2016. If approved, lesinurad will be the first selective uric acid reabsorption inhibitor (SURI) to treat patients with inadequately controlled gout in Europe. Lesinurad is also under review in the United States.
- • On October 23, 2015, AstraZeneca announced that the FDA Arthritis Advisory Committee (AAC) voted 10 to 4 to recommend the approval of lesinurad 200mg tablets for the treatment of hyperuricemia associated with gout, in combination with a xanthine oxidase inhibitor (XOI). The AAC reviewed safety and efficacy data from the pivotal Phase III combination therapy programme trials, representing the largest clinical trial data set of gout patients treated with combination urate lowering therapy. If approved, lesinurad will be the first selective uric acid reabsorption inhibitor, or SURI, in the US. It inhibits the urate transporter, URAT1, which is responsible for the majority of the renal reabsorption of uric acid.
- • On January 22, 2015, AstraZeneca announced the European Medicines Agency has accepted the Marketing Authorisation Application (MAA) for lesinurad 200mg tablets. Lesinurad is a selective uric acid reabsorption inhibitor (SURI) developed for the chronic treatment of hyperuricaemia in combination with xanthine oxidase (XO) inhibitors allopurinol or febuxostat in gout patients when additional therapy is warranted. The MAA filing was based on data from the CLEAR1, CLEAR2 and CRYSTAL pivotal Phase III combination therapy studies. CLEAR1 and CLEAR2 were 12-month, multicentre, randomised, placebo-controlled studies that evaluated the efficacy and safety of a once daily dose of lesinurad in combination with allopurinol versus allopurinol alone, in symptomatic gout patients not achieving target serum uric acid (sUA) levels on their current allopurinol therapy. CRYSTAL was a 12-month, multicentre, randomised, placebo-controlled study that evaluated the efficacy and safety of a once daily dose of lesinurad in combination with febuxostat compared to febuxostat alone in gout patients with tophi (deposits of uric acid crystals in joints and skin). The CLEAR1, CLEAR2 and CRYSTAL studies were conducted by Ardea Biosciences, a member of the AstraZeneca Group.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2015-12-22
UE authorization: 2016-02-19
Favourable opinion UE: 2015-12-17
Favourable opinion USA: 2015-10-23
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
