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Date: 2018-06-28

Type of information: Positive opinion for the granting of a Market Authorisation in the EU

Product name: Duzallo®

Compound: lesinurad and allopurinol

Therapeutic area: Inflammatory diseases

Action mechanism:

  • uric acid reabsorption inhibitor/purine analog/selective uric acid re-absorption inhibitor (SURI). 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.
  • Allopurinol is a purine analog. It inhibits xanthine oxidase and blocks the conversion of the oxypurines hypoxanthine and xanthine to uric acid. This compound is the current standard of care for the treatment of hyperuricemia associated with gout.
  • Duzallo® combines allopurinol, with the most recent FDA-approved treatment for this condition, lesinurad. This fixed-dose combination provides a dual mechanism of action in a single tablet that can address both underlying causes of hyperuricemia – overproduction and underexcretion of serum uric acid.  Allopurinol reduces the production of uric acid ; lesinurad increases renal excretion of uric acid by selectively inhibiting the action of URAT1, the uric acid transporter responsible for the majority of renal uric acid reabsorption.

Company: Ironwood Pharmaceuticals (USA - MA) Gruenenthal (Germany)

Disease:

  • hyperuricemia associated with gout in patients who have not achieved target serum uric acid (sUA) levels with a medically appropriate daily dose of allopurinol alone

Latest news:

  • • On June 28, 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Duzallo®, intended for the treatment of hyperuricaemia in gout patients. The applicant for this drug is Gruenenthal. Duzallo® will be available as film-coated tablets (300 mg/200 mg and 200 mg/200 mg). The benefit of Duzallo® is its ability to lower the level of uric acid in plasma and urine through increased uric acid excretion and decreased uric acid production. The most common side effects are influenza, gastro-oesophageal reflux disease, headache and increased blood creatinine.
  • • On August 21, 2017, Ironwood Pharmaceuticals announced that Duzallo® (lesinurad and allopurinol) was approved by the FDA as a once-daily oral treatment for hyperuricemia associated with gout in patients who have not achieved target serum uric acid (sUA) levels with a medically appropriate daily dose of allopurinol alone. Duzallo® is not recommended for the treatment of asymptomatic hyperuricemia.
  • The FDA approval of Duzallo® was based on the clinical program supporting the Zurampic® (lesinurad) new drug application (NDA) and a pharmacokinetic study that evaluated the bioequivalence of the fixed-dose combination of lesinurad and allopurinol compared to co-administration of separate lesinurad and allopurinol tablets. The efficacy and safety of lesinurad plus allopurinol were demonstrated in two pivotal Phase III clinical trials, CLEAR 1 (n=402) and CLEAR 2 (n=410), which supported the Zurampic® NDA. In clinical trials of adult patients with gout who failed to achieve target sUA levels on allopurinol alone, lesinurad in combination with allopurinol nearly doubled the number of patients who achieved sUA target of <6 mg/dL at month 6, reduced the mean sUA level to <6 mg/dL by month 1 and maintained that level through month 12. The most common adverse reactions in clinical trials were headache, influenza, higher levels of blood creatinine (a measure of kidney function), and heartburn (acid reflux). Duzallo® has a boxed warning regarding the risk of acute renal failure.
  • The Duzallo® NDA was submitted by Ardea Biosciences, Inc. on behalf of Ironwood. Ironwood expects Duzallo® to be commercially available early in the fourth quarter of 2017.
 

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: 2017-08-21

UE authorization:

Favourable opinion UE: 2018-06-28

Favourable opinion USA:

Orphan status USA:

Orphan status UE:

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

Is general: Yes