Amgen’s Efficacy of AMG 510 to KRAS G12C Mutant Critical for Future Directions and Business Investments

At the 2019 World Conference on Lung Cancer (WCLC), Amgen declared the efficacy of AMG 510 for treating non-small cell lung cancer (NSCLC) with KRAS G12 C-mutated solid tumors. Amgen also announced prospective directions for AMG510 through academic scholars and reports the few limitations on official drug release as evidence for potential investors to consider the value of AMG 510. KRAS is part of the RAS gene family which contains “the most frequently mutated oncogenes in human cancers” (PRNewswire, 2019). KRAS, in particular, is responsible for 3~5% of colorectal cancer, 13% of non-small cell lung cancers, and 1~2% of many other solid tumors. KRAS G12 C-mutated solid tumor is especially difficult to treat because its protein structure omits small molecule binding pocket. In other words, targeting KRAS G12C protein at a specific site to inhibit mutant gene’s deteriorating effects to patients is not possible. Fortunately, Amgen has overcome this challenge through substantial data collection and analysis. In closing their comments at WCLC, Amgen elaborated on the company’s future and any possible issues that AMG 510’s experimental success on lung cancer treatment might have.

Proof of Correlated Response of KRAS G12C Mutant Patients to AMG 510

Amgen presented proof of AMG 510’s efficacy at both the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) and the 2019 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer. The 55th Annual Meeting showed the data from Phase I Study in which patients with KRAS G12C mutant solid tumors and pretreated with at least two lines of treatments based upon their tumor types and stages of disease. The Phase I data primarily tested on the safety of different concentrations of drug at 180mg, 360mg, 720mg, and 960 mg for four different groups of eligible patients, respectively, once a day. Phase I also presented data on the “pharmacokinetics, objective response rate, duration of response and progression-free survival” (PRNewswire, 2019). The data presented at WCLC are from the follow-up experiment done with a larger group of 34 eligible patients. This additional study showed a disease control rate of 100% with over 50% of the 23 evaluable patients from the original sample population of 34 patients. Among the total 34 patients who participated in the experiment, they all responded with low or no dose-limiting toxicities and adverse effects when discontinuing administration of AMG 510.

These findings for AMG 510 on NSCLC with KRAS G12C mutant genes fascinate academics. RamaswamyGovindan, M.D., principle investigator and professor at WashingtonUniversity School of Medicine in St. Louis, confirms AMG 510 has the potential to bridge the knowledge gap of treating KRAS G12C mutant apparent in the absence of approved therapy for specific driver mutations of cancer since AMG 510 has the potential to become a form of treatment. Channing Der, professor at the Lineberger Comprehensive Cancer Center at the University of North Carolina Chapel Hill echoes Govindan’s evaluation of AMG 510; he comments that the data presented by Amgen is “a clear breakthrough” (Cortez, 2019). However, he questions the extent of the benefit on patients, for example, of how AMG 510 can genuinely help patients live longer; without evidence of this, AMG 510 should not be considered a success.

Medical, Political, Economic, and Legislative Challenges on Post-Experimental Success of AMG 510

Aside from only experimental proof of increasing KRAS G12C patients’ life expectancy, other questions and uncertainties prevent AMG 510’sofficial release, including medical, political, economic and legislative impediments. For example, the limitations on applying AMG510 safely and effectively on all patients with KRAS G12C mutant can be attributed to the sheer complexity of human bodies and the inability to holistically model them with computers, cell culture systems, or animal models (PRNewswire, 2019). As for political and economic challenges, Amgen has to confront regulations and cater marketing both internationally and domestically. Specific situations might entail “difficulties or delays in manufacturing products and global economic conditions,” “the adoption of tax legislation or exposure to additional tax liabilities,” or “the length of time [required] for [Amgen] to complete clinical trial[s] [to] obtain regulatory approval for product marketing” (PRNewswire, 2019). In terms of legislative restriction, Amgen may encounter government investigation, litigation, product liability claims, and disputes over product and technological patents from Amgen’s competitors can possibly affect the effectiveness of AMG 510 to be released (PRNewswire, 2019). Therefore, Amgen will face more challenges if it continues toward an ambitious commitment: to unlock “the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics” and to grow “to be one of the world’s leading independent biotechnology companies” (PRNewswire, 2019).

Reference

1. https://wwwext.amgen.com/media/news-releases/2019/09/amgen-announces-new-clinical-data-evaluating-novel-investigational-krasg12c-inhibitor-in-larger-patient-group-at-wclc-2019/

2. https://wwwext.amgen.com/media/news-releases/2019/09/amgen-announces-new-clinical-data-evaluating-novel-investigational-krasg12c-inhibitor-in-larger-patient-group-at-wclc-2019/

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