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Home LUMYKRAS® (Sotorasib) Receives Positive CHMP Opinion for KRAS G12C-Mutated Advanced NSCLC in the EU

LUMYKRAS® (Sotorasib) Receives Positive CHMP Opinion for KRAS G12C-Mutated Advanced NSCLC in the EU

Nov 13, 2021 03:28 CST Updated 03:28
Amgen

Developer of Treatment Drugs for Serious Diseases

Committee for Medicinal Products for Human Use

Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.

European Commission

The European Commission, abbreviated as the EU Commission, is a supranational body under the European Union. Within the EU political system, the European Commission primarily undertakes executive tasks, thus being roughly equivalent to the government in a national system. However, the European Commission has other functions as well. In particular, except for the few circumstances specified in the treaties, the European Commission is the only institution with legislative power in the EU legislative process.


November 12, 2021 /BioValleyBIOON/ -- Amgen recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending conditional approval.Targeted anticancer drug Lumykras (sotorasib): For the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) whose disease has progressed after receiving at least one prior systemic therapy and who carry the KRAS G12C mutation.. Now, the CHMP opinion will be submitted to the European Commission (EC) for review, which typically makes a final decision within 2 months. If approved,Lumykras Will Become the First Targeted Therapy for KRAS G12C Mutation in the EU, which is the most common in NSCLCBiomarkerOne. It is estimated that approximately 13-15% of European NSCLC patients carry the KRAS G12C mutation.

Sotorasib is the first KRAS G12C inhibitor to enter clinical development and was approved by the U.S. FDA in May 2021 (brand name: Lumakras) for the treatment of patients who have previously received at least one systemic therapy.FDAApproved testing methods confirm the presence of KRAS G12C mutations in adult patients with locally advanced or metastatic NSCLC.Clinical TrialIn China, sotorasib treatment demonstrated rapid, deep, and durable anti-cancer activity with a positive benefit-risk profile.

In ChinaSotorasib was approved by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in February this year.Included in "Breakthrough Therapy Designation"This designation is for its use in treating patients with locally advanced or metastatic NSCLC who have previously received at least one systemic therapy and carry the KRAS G12C mutation.

It is worth mentioning that,Lumakras is the first KRAS-targeted therapy approved after nearly 40 years of research, and is the first and only targeted therapy approved for the treatment of patients with locally advanced or metastatic NSCLC harboring the KRAS G12C mutation.NSCLC is the most common type of lung cancer, accounting for approximately 2.2 million new cases globally each year.Diagnosis84% of lung cancer cases. KRAS mutation is the most common driver mutation in NSCLC and has now become a "druggable" target. KRAS mutations account for approximately 25% of NSCLC mutations; among them, KRAS G12C is the most common type of KRAS mutation in NSCLC. About 13% of non-squamous NSCLC patients carry the KRAS G12C mutation.

The positive review opinion of the CHMP is based on the positive results of the Phase 2 CodeBreaK 100 study cohort of patients with advanced NSCLC. This study is the largest to date in the patient population carrying the KRAS G12C mutation.Clinical TrialData from a cohort of 124 patients with KRAS G12C mutation-positive NSCLC whose disease progressed after receiving immunotherapy and/or chemotherapy showed that Lumakras has good efficacy and tolerability.

In this cohort, patients treated with 960mg of Lumakras orally once daily,The objective response rate (ORR) was 37.1% (95% CI: 28.6-46.2), the median duration of response (DoR) was 11.1 months, the disease control rate (DCR) was 80.6%, and the median overall survival (mOS) was 12.5 months.The most common treatment-related adverse reactions were diarrhea (32%), nausea (19%), and elevated transaminase (ALT and AST) levels (each 15%). The most common severe (≥Grade 3) treatment-relatedAdverse ReactionsIncluding elevated alanine aminotransferase (ALT; 6%) levels, elevated aspartate aminotransferase (AST; 6%) levels, and diarrhea (4%). Only 7% of patients discontinued treatment due to treatment-related adverse events.

Sotorasib (AMG510) Chemical Structure (Image Source: selleck.cn)

KRAS is one of the first oncogenes discovered, with mutations present in approximately 1/4 of human tumors, making it one of the most well-defined targets in the field of oncology drug development. However, despite its promising potential, KRAS has long been nearly impossible to target due to the protein's featureless, nearly spherical structure, which lacks obvious binding sites, making it difficult to synthesize a compound that can specifically bind to and inhibit its activity. This has also made KRAS a...TumorA synonym for "undruggable" targets in the field of drug development.

Sotorasib (AMG 510) is one of the first small-molecule inhibitors to successfully target KRAS and enter clinical development in humans, specifically inhibiting KRAS proteins with the G12C mutation.Sotorasib specifically and irreversibly inhibits the pro-proliferative activity of the G12C mutant KRAS protein by locking it in an inactive GDP-bound state.

By developing sotorasib, Amgen has taken on one of the most formidable challenges in cancer research over the past 40 years. Sotorasib is the first KRASG12C inhibitor to enter clinical trials. Currently, Amgen is advancing the largest and most extensive global KRASG12C inhibitor development program at an unparalleled speed, exploring more than 10 drug combinations.Clinical TrialSpanning five continents, Lumakras/Lumykras has treated more than 3,000 patients worldwide through clinical development programs and commercial use to date. (Bioon.com)