Pfizer's Antifungal Drug Isavuconazole Capsules Granted Second Indication in China for Invasive Aspergillosis in Adults

On January 15, the latest announcement on the official website of China's National Medical Products Administration (NMPA) revealed that Pfizer's newly introduced anti-infective drug, Isavuconazole Sulfate Capsules, had received approval for another new indication. Notably, on December 16, 2021, this product was just approved in China for the treatment of adult invasive mucormycosis. Based on publicly available information, the newly approved indication for Isavuconazole in China is speculated to be: treatment of adult invasive aspergillosis.

Screenshot source: NMPA official website

Isavuconazole (Cresemba), jointly developed by Astellas and Basilea Pharmaceutica, is a triazole antifungal drug administered intravenously and orally. In 2015, Isavuconazole received approval from the U.S. FDA for the treatment of invasive aspergillosis and mucormycosis. On December 16, 2021, the drug was approved for marketing in China. According to a press release by Pfizer at the time, this made it the first oral antifungal medication approved in China for the treatment of adult invasive mucormycosis.

In terms of mechanism of action, isavuconazole inhibits cytochrome P450 (CYP)-mediated 14α-lanosterol demethylation, which suppresses ergosterol synthesis in the fungal cell membrane, leading to the accumulation of the toxic intermediate lanosterol. This causes disruption of the structure and function of the fungal cell membrane, increased permeability, and cell death. Compared with other azole drugs, the unique molecular structure of isavuconazole allows the triazole ring to orient and bind to the binding pocket of the fungal CYP51 protein, thereby providing it with a broad antifungal spectrum. It exhibits good antimicrobial activity against a variety of fungi, including azole-resistant strains.

According to literature reports, isavuconazole has a broad antibacterial spectrum. In vitro studies and clinical trials suggest it has antibacterial activity against molds, yeasts, dimorphic fungi, and some rare fungi. It is clinically effective for infections in special locations, such as the central nervous system. Its blood concentration is stable, with good safety and tolerability, and it has few drug-related adverse reactions with long-term use. Currently, several European guidelines have recommended isavuconazole as a first-line treatment for invasive aspergillosis in patients with hematological diseases.

In the United States, isavuconazole is marketed by Astellas, the authorized partner of Basilea Pharmaceutica. In July 2017, Pfizer reached an agreement with Basilea Pharmaceutica to obtain exclusive commercialization rights for isavuconazole in Europe (excluding Nordic countries). In December of the same year, Pfizer once again reached an agreement with Basilea Pharmaceutica to acquire exclusive rights for the research, distribution, and sale of isavuconazole in China and 16 other Asia-Pacific countries (excluding Japan).

Invasive Fungal Disease: A New Treatment Option with IsavuconazoleInvasive fungal disease is a common complication with high morbidity and mortality in immunocompromised patients, such as those with advanced HIV infection and cancer. The incidence of this disease has been increasing annually, making it one of the major public health challenges faced globally today. For patients diagnosed with invasive aspergillosis and mucormycosis, the currently available treatment options are very limited, and resistance to other existing therapies is also on the rise. The emergence of isavuconazole provides an important new treatment option for patients suffering from these life-threatening fungal infections.

References:

[1] Information on drug approval certificates pending collection from the National Medical Products Administration (NMPA) of China on January 5. Retrieved Jan 5, 2022, from https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20220105143701157.html

[2] Jiang Yingkui, Zhu Liping. Research Progress of the New Antifungal Drug Isavuconazole [J]. Progress in Pharmaceutical Sciences, 2021, 45(06): 427-432.

[3] Pfizer signs agreement for the development and sale of CRESEMBA® (isavuconazole) in China and the Asia-Pacific region. Retrieved Dec. 1, 2017, from https://mp.weixin.qq.com/s/JjsW-ENth9ky-hrVLBJWOw

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