Takeda's Vonoprazan (Takecab) Submits Second New Indication Application in China Within Six Months of Initial Approval

By Xiao Yaowan

On June 4, the official website of the Center for Drug Evaluation (CDE) showed that Takeda Pharmaceutical Company Limited had submitted a marketing application in China for new indications of its drug Vonoprazan Fumarate Tablets (brand name: Vocinti), involving two acceptance numbers, which have been accepted by the CDE. Notably, this is the second application for new indications of Takeda’s Vonoprazan Fumarate Tablets in China within less than six months after its initial approval, reflecting an unusually rapid pace of market expansion among foreign pharmaceutical companies.

Source: CDE

The First P-CAB Approved for Entry into the Chinese Market

In February 2015, Takeda’s vonoprazan fumarate tablets were launched in Japan for the treatment of acid-related disorders, including reflux esophagitis, gastric ulcers, duodenal ulcers, prevention of recurrence of gastric or duodenal ulcers during treatment with low-dose aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs), and eradication of Helicobacter pylori. According to Takeda Pharmaceutical Company Limited’s performance report, sales of vonoprazan fumarate tablets reached USD 668 million in 2019, representing a year-on-year increase of 24.9%.

In March 2018, the Center for Drug Evaluation of the National Medical Products Administration (NMPA) officially accepted Takeda’s first marketing application in China for Vonoprazan Fumarate Tablets. On December 18, 2019, Vonoprazan Fumarate Tablets were officially approved by the National Medical Products Administration (NMPA) for the treatment of reflux esophagitis (RE), under the brand name Vocinti.

Vonoprazan Fumarate Tablets belong to the class of potassium-competitive acid blockers (P-CABs). By blocking the K+ channel of H+,K+-ATPase, they competitively inhibit the binding of K+ to this enzyme. The drug remains in gastric parietal cells for an extended period, thereby rapidly suppressing gastric acid secretion. With a novel mechanism of action, it is the first potassium-competitive acid blocker (P-CAB) approved for entry into the Chinese market.

A New Choice for Patients in China

Reflux Esophagitis (RE) is a common disease of the digestive system, characterized by heartburn and acid regurgitation caused by the reflux of gastric contents. It may be accompanied by extra-esophageal symptoms and involves erosion of the esophageal mucosa, significantly affecting patients' quality of life and sleep.

Prior to the domestic approval of Takeda’s vonoprazan fumarate tablets, proton pump inhibitors (PPIs) were the most widely used acid-suppressing agents. However, these drugs demonstrated suboptimal clinical efficacy, failing to meet the acid suppression requirements for the treatment of reflux esophagitis (RE).

As an acid-suppressive drug with a novel mechanism of action, vonoprazan fumarate tablets have demonstrated numerous advantages in clinical studies, characterized by full efficacy from the first dose, sustained acid suppression, and convenient administration. The approval and market launch of vonoprazan fumarate tablets in China provide a new therapeutic option for the clinical management of reflux esophagitis (RE), holding promise for alleviating patient symptoms, promoting mucosal healing, and ultimately achieving a substantial improvement in quality of life.

Takeda’s Clinical Development Strategy in the Chinese Market

In China’s clinical trial registry, Takeda has six clinical trials of vonoprazan fumarate tablets, with indications covering duodenal ulcer, erosive esophagitis, and gastric ulcer. Among the three completed Phase III clinical trials, Takeda developed this new drug for the treatment and maintenance therapy of erosive esophagitis, as well as for duodenal ulcer. It is speculated that these trials included the new indications submitted in two separate marketing authorization applications in April and June 2020, respectively.

Source: CHINADRUGTRIALS

Currently, another clinical study of Takeda’s vonoprazan fumarate tablets is in Phase III, planning to enroll 425 subjects in China to compare the efficacy of Helicobacter pylori (HP) eradication therapy using bismuth-containing quadruple therapy combined with vonoprazan versus esomeprazole in HP-positive subjects with clarithromycin resistance.

P-CABs Under Development in China

According to investigations, the compound patent for Takeda’s vonoprazan fumarate tablets in China is set to expire in 2026. Currently, the development of investigational drugs based on potassium-competitive acid blockers (P-CABs) in China can be broadly categorized into two types: one focuses on the development of generic vonoprazan, and the other on the development of novel drugs within the same class.

In the first scenario, Chia Tai Tianqing and Shandong New Time Pharmaceutical have completed their respective human bioequivalence studies for generic vonoprazan fumarate tablets. Bioequivalence trials for Hangzhou Huadong Medicine and Shandong Fuchuang Pharmaceutical are currently ongoing. The indications involved include: treatment of gastric ulcers, duodenal ulcers, and reflux esophagitis; prevention of recurrence of gastric or duodenal ulcers during low-dose aspirin therapy; prevention of recurrence of gastric or duodenal ulcers during non-steroidal anti-inflammatory drug (NSAID) therapy; and combination therapy for Helicobacter pylori infection associated with the following conditions: gastric ulcers, duodenal ulcers, gastric MALT lymphoma, idiopathic thrombocytopenic purpura, endoscopic treatment of early gastric cancer, and gastritis with Helicobacter pylori infection.

In the development of new drugs, Luoxin Pharmaceutical entered into a collaboration agreement with CJ Health Care in 2015, obtaining the rights to develop, manufacture, and commercialize CJ Health Care’s investigational P-CAB drug LXI-15028 in mainland China. In December 2019, LXI-15028 demonstrated non-inferiority to esomeprazole in a multicenter, randomized, double-blind, parallel-group Phase III clinical trial.

In addition to Luoxin Pharmaceutical, X842, jointly developed by Tairuishengnuo and Switzerland’s Cinclus Pharma AG, and Kefei Ping Pharmaceutical’s new drug, konorazan hydrochloride tablets, are currently in Phase II clinical trials.