In last year, according to data collated from the National Medical Products Administration (NMPA) official website, a total of more than 80 new drugs were granted inaugural approval within the domestic market. Observing the molecular categorization of these approved entities, small molecule therapeutics constituted the majority, representing an overwhelming 75%. Among these, which compounds are considered significant breakthroughs, and what ramifications have their approvals engendered?
Mobocertinib (Brand Name: Exkivity)
Approval Date: January 13, 2023
Pharmaceutical Company: Takeda
Indications: Indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) exhibiting progression during or subsequent to platinum-containing chemotherapy, who harbor epidermal growth factor receptor (EGFR) exon 20 insertion mutations (EGFR ex20ins)
Within the domestic landscape, the incidence of EGFR ex20ins mutations constitutes approximately 2.3% of all NSCLC cases in China, positioning it as the third most common EGFR mutation. Compared to more prevalent EGFR mutations, patients with advanced NSCLC harboring the EGFR ex20ins mutation exhibit inferior survival outcomes, with a 5-year survival rate mere at 8%. Currently, there exists a significant void in effective targeted therapeutic strategies for this mutation in clinical settings.
The market introduction of Mobocertinib provides a novel therapeutic option for patients with advanced NSCLC harboring the EGFR ex20ins mutation in China. Specifically engineered for EGFR ex20ins, Mobocertinib incorporates an innovative isopropyl ester structure, forming a flexible monocyclic core, enabling more efficacious binding with EGFR ex20ins, thereby offering precise selectivity and heightened affinity.
Mobocertinib received accelerated approval from the FDA (September 15, 2021) and conditional approval from the NMPA, predicated on the outcomes of the EXKIVITY I/II phase single-arm trial.
This trial encompassed 114 patients with EGFR ex20ins mutation NSCLC who had previously undergone platinum-based treatment. The data revealed that the median Overall Survival (OS) in the platinum-based chemotherapy cohort (PPP) achieved an impressive 24 months. Despite its remarkable efficacy, the necessity for phase III confirmatory trials remains, due to its single-arm trial design.
However, the phase III confirmatory trial, Exclaim-2, was terminated due to Mobocertinib's lack of efficacy. Consequently, on October 2 of this year, Takeda announced its intention to collaborate with the FDA to voluntarily withdraw Mobocertinib in the United States. Its potential withdrawal from the Chinese market remains uncertain.
Keverprazan Hydrochloride (Brand Name: Beiwen)
Approval Date: February 15, 2023
Pharmaceutical Company: Jiangsu Carephar Medicine/Fosun Pharma
Indications: For the treatment of duodenal ulcers and reflux esophagitis
Acid-related disorders (ARDs) denote gastrointestinal diseases arising from excessive gastric acid secretion or abnormal sensitivity to gastric acid, including gastroesophageal reflux disease (GERD) and peptic ulcer disease (PUD). The suppression of gastric acid secretion stands as the cornerstone of current ARD therapeutic strategies.
Since the market debut of the first proton pump inhibitor (PPI), Omeprazole, in 1988, the treatment paradigm for ARDs such as reflux esophagitis has witnessed a milestone breakthrough. Nevertheless, PPIs exhibit limitations such as slow onset of action, elevated incidence of nocturnal acid breakthrough, and stringent preparation requirements, hence the pressing demand for the introduction of next-generation acid-suppressive medications.
Keverprazan Hydrochloride represents a pioneering class of potassium-competitive acid blockers (P-CABs), inhibiting gastric acid secretion by binding to the potassium binding site on the H+-K+-ATPase. Owing to its ability to bind both active and resting proton pumps, Keverprazan Hydrochloride demonstrates rapid onset of action and potent acid-suppressive effects. Moreover, it accumulates in high concentrations within gastric parietal cells and dissociates slowly, ensuring sustained and potent anti-secretory activity, unaffected by food intake.
To date, three P-CAB medicat...
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