Takeda Submits European Marketing Authorisation Application for Azilsartan Medoxomil

Takeda Pharmaceutical Company Limited (Takeda) today announced that Takeda Global Research & Development Centre (Europe), Ltd. submitted a Marketing Authorisation Application (MAA) for azilsartan medoxomil (development code: TAK-491), an angiotensin II receptor blocker (ARB), to the European Medicines Agency (EMA) for the treatment of essential hypertension. The EMA has confirmed that the submission has been validated for assessment.
High blood pressure, or hypertension, was responsible for 7.6 million preventable deaths worldwide in 2001. Almost half (44 percent) of the adult population in Europe is affected by hypertension - much (approximately 60 percent) higher than in the United States and Canada. Discovered by Takeda, azilsartan medoxomil is a prodrug of the active moiety azilsartan, which lowers blood pressure by blocking the action of a vasopressor hormone, angiotensin II. The discovery and development of azilsartan medoxomil continues Takeda's commitment to the treatment of hypertension, and builds upon the company's long-standing clinical experience with its previously discovered antihypertensive agent candesartan.
The MAA submission for azilsartan medoxomil monotherapy was supported by positive results from a clinical development program which included nine phase 3 clinical trials in which approximately 7000 subjects with essential hypertension were enrolled of whom 4814 unique subjects received at least 1 dose of azilsartan medoxomil. The safety and efficacy of azilsartan medoxomil was studied for initial therapy as a once-daily oral monotherapy or for co-administration with other antihypertensive medications, including the diuretics chlorthalidone and hydrochlorothiazide, and the calcium channel blocker, amlodipine. It was also studied in comparison with olmesartan medoxomil, valsartan and ramipril.
Results from the phase 3 clinical trials showed azilsartan medoxomil successfully met the primary endpoints: change in 24-hour mean systolic blood pressure (SBP) by ambulatory blood pressure monitoring (ABPM) and key secondary endpoint, clinic SBP, producing a statistically significant and clinically meaningful lowering of blood pressure in subjects with essential hypertension.(4) The most commonly reported treatment-related adverse reactions in phase 3 monotherapy placebo-controlled clinical trials were dizziness, increased blood creatine phosphokinase, diarrhoea, fatigue and peripheral oedema.(8)
In April 2010, Takeda submitted a New Drug Application for azilsartan medoxomil to the U.S. Food and Drug Administration. The filing is currently under regulatory review.
"This MAA represents a significant milestone for our company and carries positive clinical implications for both physicians and patients for the treatment of essential hypertension," said Suhail Nurbhai, M.D., vice president & head of Clinical Science, Takeda Global Research & Development Centre (Europe), Ltd. "Based on the encouraging results of phase 3 clinical studies demonstrating the compound's efficacy, safety and tolerability, we believe azilsartan medoxomil, once approved, will provide clinicians in Europe with an important additional treatment for patients with essential hypertension."
"Takeda is committed to developing treatments for patients with cardiovascular disease and for use by healthcare providers for their patients," said Steve Coles, Ph.D., managing director, Takeda Global Research & Development Centre (Europe), Ltd. "We are proud to continue expanding our cardiovascular expertise in Europe to potentially address this serious health problem."