Janssen Submits IND Application in China for Lazertinib, a Third-Generation EGFR-TKI Acquired for Over $1.25 Billion

Source | Medical Insights

Today, the latest public announcement from the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration revealed that Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, has submitted an Investigational New Drug (IND) application in China for lazertinib tablets, which has been accepted by the CDE. Lazertinib is a third-generation tyrosine kinase inhibitor (TKI) currently under development for the treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR gene mutations. Notably, Janssen Pharmaceuticals acquired the development and commercialization rights to this drug from a South Korean pharmaceutical company in 2018 for over USD 1.25 billion.

Data Source: CDE Official Website

As a third-generation tyrosine kinase inhibitor (TKI), lazertinib is being developed for the treatment of patients with non-small cell lung cancer (NSCLC) harboring EGFR gene mutations. It reportedly exhibits high specificity for EGFR with specific activating mutations and is capable of crossing the blood-brain barrier. This highly potent, oral, irreversible TKI is currently under clinical evaluation as a first-line and second-line therapy for patients with NSCLC.

This drug was initially developed by the South Korean pharmaceutical company Yuhan Corporation. In 2018, Janssen Pharmaceuticals entered into an agreement with Yuhan Corporation regarding lazertinib. Under the terms of the agreement, Yuhan received a $50 million upfront payment and is eligible to receive up to $1.205 billion in development and commercialization milestone payments, as well as royalties on future sales. Janssen Pharmaceuticals will assume responsibility for the development, manufacturing, and commercialization of lazertinib and holds exclusive global rights to the drug, excluding South Korea.

Results from the phase 1/2 clinical trial presented at the 2018 ASCO Annual Meeting demonstrated that lazertinib achieved an objective response rate (ORR) of 61% in patients with NSCLC who had developed resistance to EGFR-TKIs, and an intracranial ORR of 55% in patients with brain metastases.

As is well known, lung cancer is the leading cause of cancer-related mortality. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. About 75% of NSCLC patients are diagnosed at an advanced stage, with a five-year survival rate of only 5%. EGFR is a growth factor receptor protein that promotes cell growth and division; mutations in EGFR can lead to the formation of cancer cells and play a driving role in the development of lung cancer.

Public data indicate that EGFR mutations occur in 10%–35% of NSCLC cases globally, while approximately 50% of NSCLC patients in China harbor EGFR gene mutations. Consequently, many targeted therapies for lung cancer under development worldwide aim to suppress tumor growth by inhibiting the activity of mutant EGFR.

Several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have previously been marketed, bringing clinical benefits to many patients. However, acquired resistance following TKI therapy leads to disease progression in some patients, approximately half of whom harbor the T790M mutation in the EGFR gene. Consequently, the development of third-generation TKIs has focused on inhibiting kinase activity specifically targeting the EGFR T790M mutation. Currently, multiple third-generation TKIs have been approved worldwide. For instance, AstraZeneca’s small-molecule targeted therapy, Tagrisso (osimertinib), was the first drug globally approved for the treatment of lung cancer patients carrying the EGFR T790M mutation.

Lazertinib is also a third-generation TKI. It is reported that, due to its high efficacy, selectivity for EGFR mutations, irreversible binding, brain penetration, and oral activity, it is considered to have the potential as a first-line treatment. This marks the drug’s first clinical trial application in China; if approved, clinical studies in China are expected to be initiated.

We hope that the clinical development of this drug will proceed smoothly, bringing new treatment options to patients as soon as possible.

Original Title: Janssen’s Third-Generation TKI Lung Cancer Targeted Drug Files for Clinical Trial Approval in China, Securing Over $1.25 Billion!

▽Follow [WuXi AppTecDe】WeChat Official Account