Qilu Pharmaceutical Submits NDA for Its First Class 1 New Drug, Iruok Tablet (WX-0593), an ALK/ROS1 Inhibitor

Text | Jia Yi

On July 24, the CDE website indicated that Qilu Pharmaceutical's marketing authorization application for a Class 1 innovative drug, “Yiluaoke Tablets,” has been submitted and accepted. This is the first Class 1 new drug marketing application submitted by Qilu Pharmaceutical. According to Qilu Pharmaceutical's R&D pipeline, the drug is likely the ALK/ROS1 inhibitor WX-0593. Click here to view the acceptance number.

WX-0593: May be the second Chinese ALK inhibitor submitted for marketing approval

WX-0593 is a novel ALK/ROS1 inhibitor independently developed by Qilu Pharmaceutical. It inhibits the kinase activity of wild-type ALK and ALK inhibitor-resistant mutants across various fusion types, while effectively suppressing the kinase activity of ROS1 across different fusion variants. Studies have shown that WX-0593 exhibits antitumor activity in ALK-positive or ROS1-positive non-small cell lung cancer (NSCLC) with an acceptable safety profile. Dosing regimens up to 180 mg demonstrate highly favorable pharmacokinetic parameters and safety.

According to the Insight database, WX-0593 was first submitted for clinical trial approval in May 2016, and the initiation of its clinical trials was first publicly announced in October 2017. Currently, four clinical trials have been registered and initiated, including a Phase II clinical trial for the second-line treatment of ALK/ROS1-positive NSCLC and a Phase III clinical trial for the first-line treatment of ALK-positive NSCLC patients.

In October 2019, Qilu Pharmaceutical initiated a Phase III clinical trial (CTR20191231) comparing WX-0593 tablets with crizotinib for the treatment of ALK-positive non-small cell lung cancer, enrolling 330 patients in China who had not previously received any systemic antitumor therapy other than chemotherapy, with progression-free survival (PFS) as the primary endpoint and secondary endpoints including efficacy parameters such as OS, ORR, and DOR, as well as safety parameters such as AEs and TEAEs.

At the 2019 ESMO Congress, Qilu Pharmaceutical presented the Phase I clinical data for WX-0593. The study enrolled a total of 54 patients with advanced ALK/ROS1-positive solid tumors who were either treatment-naïve or had failed standard therapy. Patients were assigned to multiple dose cohorts ranging from 30 to 300 mg and administered WX-0593 tablets once daily to evaluate the safety and tolerability, pharmacokinetic profile, and preliminary efficacy of the drug.

The results demonstrated that WX-0593 exhibited significant antitumor activity at a starting dose of 30 mg, with the 120 mg and 180 mg doses showing the most pronounced efficacy. In ALK inhibitor-naïve patients, the ORRs were 85.7% (6/7) and 75% (3/4), respectively, while in crizotinib-resistant patients, the ORR was 50% (1/2 and 3/6). Among ROS1-positive patients, both of the two crizotinib-naïve patients enrolled in the 180 mg cohort achieved an objective response. These findings highlight the therapeutic advantages of WX-0593 tablets, including a low starting dose, rapid onset of action, and a wide safety window, offering a promising new treatment option for patients with advanced ALK-positive and ROS1-positive NSCLC.

Objective Response Rate (ORR) Results

Currently, four ALK inhibitors have been approved for marketing in China, including three imported drugs: crizotinib (Pfizer, January 2013), ceritinib (Novartis, May 2018), and alectinib (Roche, August 2018), as well as one domestically developed innovative drug, ensartinib (Betta Pharmaceuticals, October 2020). The first three have already been included in the Class B directory of the national medical insurance reimbursement list through negotiation. Additionally, Pfizer's lorlatinib and Takeda's brigatinib are currently under marketing application.

Additionally, several Chinese companies also have clinical-stage innovative drug programs for ALK inhibitors. Apart from Betta Pharmaceuticals, which has already secured approval, and Qilu Pharmaceutical, which has filed for marketing approval, Chia Tai Tianqing and Shouyuan Holdings are advancing the fastest and have already initiated Phase III clinical trials.

Qilu Pharmaceutical: 19 Innovative Drugs in Development

According to the Insight database, Qilu Pharmaceutical has now established an R&D pipeline comprising 19 innovative drugs. With the exception of two novel hepatitis B drugs and one anti-infective agent, the remainder are all anti-tumor drugs. With a strategic focus on biologics, these account for over 70% of the pipeline currently under development.

The three most advanced new drugs have entered Phase III clinical trials: the ALK/ROS1 inhibitor WX-0593, the PD-1 monoclonal antibody QL1604, and the EpCAM ADC moaozhu mAb.

WX-0593 is likely Yilu'aoke tablets, which is currently under marketing application. As the first innovative drug submitted for market approval by Qilu Pharmaceutical, Yilu'aoke represents a milestone. The PD-1 monoclonal antibody QL1604 has initiated five clinical trials targeting multiple malignancies, including liver cancer, gastric cancer, and MSI-H/dMMR solid tumors, and has also received clinical trial approvals for cancer types such as breast cancer and Hodgkin lymphoma. Oportuzumab monatox is an antibody-drug conjugate licensed by Qilu from Sessen Bio in July 2020 for USD 35 million, developed for the treatment of non-muscle invasive bladder cancer.

In the biologics sector, Qilu Pharmaceutical has established strategic development pipelines in monoclonal antibodies (mAbs), bispecific antibodies (bsAbs), and antibody-drug conjugates (ADCs), which feature several promising targets in the immuno-oncology field. For mAbs, the pipeline covers PD-1, TIGIT, 4-1BB, and Claudin18.2, while for bsAbs, it includes target combinations such as PD-1/CTLA-4, PD-L1/TGFβ, and PD-L1/4-1BB.