Takeda's Class 1 New Drug Azilsartan Medoxomil Potassium Tablets Nears NMPA Approval for Essential Hypertension

Author: Shibe

Source: PharmCube Info

Recently, Takeda Pharmaceutical’s marketing application for Azilsartan Medoxomil Potassium Tablets, filed under Category 5.1 (Acceptance Number: JXHS1800028), is currently in the “under review” stage and is expected to receive approval from the National Medical Products Administration (NMPA) in the near future. The drug is indicated for the treatment of essential hypertension.

Angiotensin II is converted from angiotensin I under the catalytic action of angiotensin-converting enzyme. As the primary pressor agent of the renin-angiotensin system, angiotensin II exerts various physiological effects, including promoting vasoconstriction, stimulating the synthesis and release of aldosterone, activating the heart, and enhancing renal sodium reabsorption.

Azilsartan medoxomil potassium is an angiotensin II receptor blocker independently developed by Takeda. It is an oral prodrug that is rapidly metabolized by esterases in the body to its active component, azilsartan, during absorption. Azilsartan selectively blocks the binding of angiotensin II to AT1 receptors in various tissues, such as vascular smooth muscle and the adrenal glands, thereby inhibiting the vasoconstrictive and aldosterone-secreting effects of angiotensin II. Consequently, its mechanism of action is independent of the angiotensin II synthesis pathway. The affinity of azilsartan for AT1 receptors is more than 10,000 times greater than that for AT2 receptors.

Chemical Structural Formula of Azilsartan Medoxomil Potassium

At the 13th Oriental Cardiology Conference in 2019, Takeda announced the results of a Phase III clinical study (NCT02480764) of azilsartan medoxomil potassium in Chinese patients with hypertension. The study enrolled a total of 612 patients with primary hypertension, who were randomly assigned to receive double-blind treatment for 8 weeks with either azilsartan medoxomil potassium 80 mg (n=209), azilsartan medoxomil potassium 40 mg (n=199), or valsartan 160 mg (n=204). Study endpoints included changes from baseline in seated systolic blood pressure (scSBP) and seated diastolic blood pressure (scDBP) at trough levels (22–24 hours after the previous dose) at Week 8, as well as safety.

The study results showed that at week 8, the reduction in trough seated systolic blood pressure (scSBP) was significantly greater in the azilsartan medoxomil potassium 80 mg group than in the valsartan group (-24.2 vs. -20.6 mm Hg; P=0.01), and the reduction in trough scSBP in the azilsartan medoxomil potassium 40 mg group was non-inferior to that in the valsartan group (-22.5 vs. -20.6 mm Hg; P=0.18).

A total of 257 eligible subjects were included in the ABPM (ambulatory blood pressure monitoring) subgroup analysis. The analysis results showed that at Week 8, the mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) over the 0–24 hour period (8 a.m.–7 a.m.) in the azilsartan medoxomil potassium 40 mg and 80 mg groups were both lower than those in the valsartan 160 mg group.

In terms of safety, the incidence of treatment-emergent adverse events (TEAEs) was similar across all treatment groups (52.8%–56.5%), and TEAEs were generally mild or moderate in severity. The most common treatment-related TEAE was dizziness (1.9% in the azilsartan medoxomil potassium 80 mg group; 1.5% in the azilsartan medoxomil potassium 40 mg group; 1.0% in the valsartan group).

Based on the above research results, Takeda submitted a marketing application for azilsartan medoxomil potassium to the NMPA in July 2018.

Azilsartan medoxomil potassium was first approved by the FDA for marketing in 2011. It is currently marketed in more than 15 countries worldwide, including the United States, Canada, France, and the United Kingdom. According to the NextPharma database of Medicine Cube, azilsartan medoxomil potassium generated JPY 76.7 billion in revenue for Takeda in 2019, equivalent to approximately RMB 4.8 billion.