China's First Approved KRAS G12C Inhibitor: Innovent Announces the Approval of Dupert® (Fulzerasib) by the National Medical Products Administration of China

SAN FRANCISCO and SUZHOU, China, Aug. 22, 2024 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, announces that China's National Medical Products Administration (NMPA) has approved Dupert®（fulzerasib）for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harboring KRAS G12C mutation who have received at least one systemic therapy. As China's first approved KRAS G12C inhibitor, Dupert® is Innovent's eleventh product in its commercial portfolio and is anticipated to soon benefit more lung cancer patients with the KRAS G12C mutation.

Lung cancer has one of the highest incidence and mortality rates worldwide, with non-small cell lung cancer (NSCLC) being the most common type, comprising about 85% of all lung cancer cases. KRAS mutations are common driver gene mutations in NSCLC but rarely co-exist with other driver mutations like EGFR and ALK. As a result, patients with advanced NSCLC and KRAS G12C mutations often cannot benefit from the multiple drugs currently available that target these mutations or rearrangements. After the initial standard treatment for this population, there are limited second-line options, which have low effectiveness and poor prognosis.

The NDA approval is based on the results from a single-arm registrational Phase 2 clinical study (NCT05005234) intended to evaluate the efficacy and safety of fulzerasib monotherapy in advanced NSCLC patients with KRAS G12C mutation who failed or were intolerant to the standard treatment in China. The updated data from this registration study has been published in full manuscript in the Journal of Thoracic Oncology (JTO).

As of the data cutoff date (Dec 13, 2023), a total of 116 NSCLC subjects were enrolled and evaluable. Fulzerasib was generally well-tolerated and demonstrated encouraging antitumor activity. The confirmed objective response rate (ORR) assessed by the Independent Radiology Review Committee (IRRC) was 49.1% (95% CI: 39.7-58.6). Disease control rate (DCR) was 90.5% (95%CI: 83.7, 95.2). The median duration of response (DoR) was not reached. Median progression-free survival (PFS) was 9.7 months (95%CI: 5.6-11.0), and median overall survival (OS) was not yet reached.

Professor Yi-Long Wu from Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, stated: "KRAS has long been considered an 'undruggable' target despite being a common oncogenic driver mutation. The advent of KRAS G12C inhibitors has opened new avenues for precision medicine in cancers harboring this mutation. We are proud to be part of the clinical research and development of Dupert®, the first KRAS G12C inhibitor approved in China. We hope that Dupert® will soon benefit more patients with advanced lung cancer harboring KRAS G12C mutations, driving the progress of precision treatment for lung cancer."

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "Patients with advanced NSCLC harboring KRAS G12C mutations have limited treatment options, with traditional chemotherapy offering minimal benefits. We are excited that Dupert® has become the first KRAS G12C inhibitor approved in China, marking the beginning of a new era in targeted therapy for KRAS mutations. As Innovent's eleventh drug, Dupert® further strengthens our robust oncology portfolio. Innovent will continue to leverage its leadership and expertise in oncology to drive innovation in cancer treatment and serve more patients in need."

About Dupert^® (Fulzerasib, KRAS G12C Inhibitor)

RAS protein family can be divided into KRAS, HRAS and NRAS categories. KRAS mutation are detected in nearly 90% of pancreatic cancer, 30-40% of colon cancer, and 15-20% lung cancer patients. The occurrence of KRAS G12C mutation subset is more frequently observed than those with ALK, ROS1, RET and NTRK 1/2/3 mutations combined.

Fulzerasib is a novel, orally active, potent KRAS G12C inhibitor designed to effectively target the GTP/GDP exchange, an essential step in pathway activation, by modifying the cysteine residue of KRAS G12C protein covalently and irreversibly. Preclinical cysteine selectivity studies demonstrated high selectivity of fulzerasib towards G12C. Subsequently, fulzerasib effectively inhibits the downstream signal pathway to induce tumor cells' apoptosis and cell cycle arrest.

In September 2021, Innovent and GenFleet Therapeutics entered into an exclusive license agreement for the development and commercialization of fulzerasib (Innovent R&D code: IBI351, GenFleet R&D code: GFH925) in China (including mainland China, Hong Kong, Macau and Taiwan).

In January 2023, the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for fulzerasib for the treatment of patients with advanced NSCLC harboring KRAS G12C mutation who have received at least one systemic therapy. In May 2023, the CDE of China's NMPA granted another BTD for fulzerasib for the treatment of advanced CRC patients with KRAS G12C mutation who have received at least two systemic therapies.

In August 2024, the CDE of NMPA has approved fulzerasib for the treatment of advanced NSCLC adult patients harboring KRAS G12C mutation who have received at least one systemic therapy.

About Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 11 products in the market. It has 3 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center.

Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. 

For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

Forward-Looking Statements

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions.

source: Innovent Biologics