Johnson & Johnson, Sanofi, Pfizer, and Novartis Submit Clinical Trial Applications in China for Four Innovative Imported Drugs

Source: Pharma Horizon

On June 3, the latest information on the website of the Center for Drug Evaluation (CDE) under China’s National Medical Products Administration (NMPA) showed that multiple drugs had been submitted for clinical trial approval, including four imported innovative drugs: Johnson & Johnson’s NKG2D monoclonal antibody JNJ-6430450, Sanofi’s lipid-lowering drug ezetimibe/rosuvastatin calcium tablets, Pfizer’s PDE4 inhibitor crisaborole, and Novartis’s CFTR modulator QBW251.

1. Johnson & Johnson: JNJ-64304500 Injection

JNJ-64304500 (JNJ-4500/IPH-2301/NN-8555) is an anti-NKG2D monoclonal antibody developed by Janssen, a subsidiary of Johnson & Johnson, and has not yet been approved in any country or region worldwide. This marks the first clinical trial application for this drug in China.

NKG2D is an activating receptor expressed on the surface of human natural killer cells, CD56+ T cells, and CD8+ T cells. Activation of the NKG2D receptor promotes cell proliferation and cytokine production. By inhibiting NKG2D activity, JNJ-4500 can reduce inflammatory responses in patients with Crohn's disease.

According to information on the ClinicalTrials.gov website, Janssen has completed a Phase 1 dose-escalation study of JNJ-64304500. The company is currently conducting a randomized, double-blind, placebo-controlled, multicenter Phase 2b study to evaluate the safety and efficacy of JNJ-64304500 in patients with moderate-to-severe Crohn's disease.

2. Sanofi: Ezetimibe and Rosuvastatin Calcium Tablets

Ezetimibe is a cholesterol absorption inhibitor that effectively reduces intestinal cholesterol absorption by selectively inhibiting the intestinal cholesterol transporter, thereby lowering plasma cholesterol levels and hepatic cholesterol stores. Rosuvastatin is a selective HMG-CoA reductase inhibitor; as a statin medication, it can be used in conjunction with exercise, dietary control, and weight loss to treat hypercholesterolemia and other related conditions, as well as to prevent cardiovascular disease.

Ezetimibe and Rosuvastatin Combination Drug is a lipid-lowering medication with dual action, used to treat chronic conditions caused by excessive blood lipids, such as fats, cholesterol, and triglycerides.

3. Pfizer: crisaborole (Eucrisa, Crisaborole)

Crisaborole is a non-steroidal topical PDE4 inhibitor under Pfizer. It was approved in the United States in 2016 for the treatment of mild-to-moderate eczema (also known as atopic dermatitis) in patients aged two years and older. In March this year, the FDA again approved the drug’s supplemental new drug application, expanding the minimum age limit for treating pediatric patients with mild-to-moderate atopic dermatitis from 24 months to 3 months. The drug has also been approved in Canada, Australia, and Israel.

In China, crisaborole has been included in the “Second Batch of Overseas New Drugs Urgently Needed for Clinical Use,” with the indication being mild-to-moderate atopic dermatitis in patients aged 2 years and older. The marketing application for this product was accepted by the Center for Drug Evaluation (CDE) on February 10 this year.

Atopic Dermatitis (AD) is a chronic inflammatory skin disease, commonly referred to as “eczema”—a general term for several types of skin inflammation. Atopic dermatitis is the most common form of eczema and typically onset in childhood, potentially persisting into adulthood. The pathogenesis of atopic dermatitis results from a combination of genetic, immune, and environmental factors. In atopic dermatitis, the skin develops red, scaly, and crusted raised lesions that are often intensely pruritic; scratching by patients can lead to skin swelling, cracking, and exudation of clear fluid; ultimately, the patient’s skin becomes roughened and thickened.

4. Novartis: QBW251

QBW251, a candidate drug under Novartis, is a CFTR modulator, also known as a potentiator. It stimulates the cystic fibrosis transmembrane conductance regulator (CFTR), leading to an influx of chloride ions. Chloride ions facilitate water transport, thereby reducing mucus viscosity. The drug acts on the cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C member 7, or cAMP-dependent chloride channel). QBW251 is being developed for the treatment of cystic fibrosis (CF). In early clinical trials, QBW251 has demonstrated favorable safety and efficacy profiles. This marks the second Investigational New Drug (IND) application for QBW251 in China.

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), resulting in the absence or functional impairment of the CFTR protein. Approximately 2,000 known mutations have been identified in the CFTR gene. The functional defect or absence of the CFTR protein leads to an imbalance in salt and water transport across the membranes of cells in multiple organs. In the lungs, this causes the accumulation of abnormally viscous mucus, leading to chronic pulmonary infections and progressive lung damage, ultimately resulting in death. CF is a rare, life-shortening genetic disease.

References:

[1] Center for Drug Evaluation, National Medical Products Administration of China. Retrieved June 01, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=3

[2] Ten Blockbuster New Drugs to Launch in the Next Four Years: What Is in Janssen’s Latest R&D Pipeline? Retrieved May 16, 2020, from https://mp.weixin.qq.com/s?__biz=MzAwMDA5NTIxNQ==&mid=2649983783&idx=1&sn=299407867c047ac815ecfa7f4b76f247

[3] ClinicalTrials.gov website. From https://clinicaltrials.gov/ct2/home

[4] FDA Approves New Eczema Drug Eucrisa Today. Retrieved Nov 15, 2016, from https://chuansongme.com/n/1739162752343

[5]QBW251 Is a Safe andEfficacious CFTR Potentiator for Patients with Cystic Fibrosis. Retrieved Jun 3，2020, from https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2016.193.1_MeetingAbstracts.A7789

(Original Title: Today, Four Imported New Drugs Submitted for Clinical Trial Approval in China, from Johnson & Johnson, Sanofi, Pfizer, and Novartis!)

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