AMGEN PROVIDES REGULATORY UPDATE ON STATUS OF LUMAKRAS® (SOTORASIB)

Rhea-AI Summary

Amgen (AMGN) receives a Complete Response Letter from the FDA for LUMAKRAS, confirming the dosing at 960 mg once-daily for patients with KRAS G12C-mutated NSCLC under accelerated approval.

Insights

Pharmaceutical Analyst

An FDA Complete Response Letter (CRL) typically indicates that the agency has reviewed a drug application and determined that it cannot approve it in its current form. For Amgen, this CRL for LUMAKRAS® (sotorasib) implies that while the drug remains on the market under accelerated approval, further evidence is required to gain full approval.

The requirement for an additional confirmatory study, with a deadline set for February 2028, suggests a significant investment in further clinical research. Stakeholders should note the implications of this extended timeline for full approval and the associated costs. However, the fulfillment of the dose comparison PMR is a positive step, confirming the current dosage of 960 mg daily as the standard for treatment.

This development is pivotal for Amgen’s strategic planning and resource allocation. It also affects the competitive landscape of NSCLC treatments, potentially influencing market share and revenue projections. Investors should monitor Amgen's progress on the new PMR and any interim data that may emerge.

Oncology Clinical Researcher

The KRAS G12C mutation is a specific genetic alteration found in a subset of NSCLC patients. The progression from accelerated to full approval hinges on demonstrating sustained clinical benefit in this population. The CodeBreaK 200 trial results are central to this process.

For oncologists and patients, the confirmation of the 960 mg once-daily dose provides consistency in treatment protocols. However, the new PMR for a confirmatory study indicates that the FDA requires additional evidence to substantiate the long-term efficacy and safety of LUMAKRAS.

From a clinical perspective, the extended timeline for the confirmatory study may affect treatment decisions and guidelines. It is crucial for medical professionals to stay informed about the latest data and regulatory updates to provide the best patient care.

Healthcare Industry Analyst

Amgen's LUMAKRAS represents a significant advancement in the targeted treatment of NSCLC with the KRAS G12C mutation. The FDA's action, while not uncommon in the drug approval process, can influence investor confidence and the company's stock valuation.

Given the high unmet need in NSCLC and the novelty of KRAS G12C inhibition, LUMAKRAS has the potential to capture a meaningful market segment. However, the CRL and subsequent PMR may affect sales forecasts and market penetration rates. Analysts should assess the potential impact on Amgen's revenue growth and factor in the costs and duration of additional studies.

It is also important to consider the broader implications for the pharmaceutical industry, including regulatory trends and the evolving landscape of cancer therapies. These factors can influence strategic decisions across the sector.

FDA Has Issued New Postmarketing Requirement

LUMAKRAS Dosing Confirmed at 960 mg Once-Daily for Patients With KRAS G12C-Mutated NSCLC Under Accelerated Approval

THOUSAND OAKS, Calif., Dec. 26, 2023 /PRNewswire/ -- Amgen (NASDAQ:AMGN) announced today that the U.S. Food and Drug Administration (FDA) has completed its review of the company's supplemental New Drug Application seeking full approval of LUMAKRAS^® (sotorasib). This review, which resulted in a Complete Response Letter, was based on the CodeBreaK 200 trial results for the treatment of adults with previously treated locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC). The FDA also issued a new postmarketing requirement (PMR) for an additional confirmatory study to support full approval that will be completed no later than February 2028.

In addition, the FDA concluded that the dose comparison PMR issued at the time of LUMAKRAS accelerated approval, to compare the safety and efficacy of LUMAKRAS 960 mg daily dose versus a lower daily dose, has been fulfilled. The company said LUMAKRAS at 960 mg once-daily will remain the dose for patients with KRAS G12C-mutated NSCLC under accelerated approval.

In May 2021, LUMAKRAS was the first KRAS^G12C inhibitor to receive regulatory approval in the U.S., under accelerated approval. To date, over 15,000 patients worldwide have received LUMAKRAS/LUMYKRAS through the clinical development program, early access and commercial use.

About Advanced Non-Small Cell Lung Cancer and the KRAS G12C Mutation
Lung cancer is the leading cause of cancer-related deaths worldwide, and it accounts for more deaths worldwide than colon cancer, breast cancer and prostate cancer combined.¹ 

KRAS G12C is the most common KRAS mutation in NSCLC.² About 13% of patients with non-squamous NSCLC harbor the KRAS G12C mutation.³ Unmet medical need remains high and treatment options are limited for NSCLC patients with the KRAS G12C mutation whose first-line treatment has failed to work or has stopped working. 

LUMAKRAS^® (sotorasib) U.S. Indication
LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy. 

This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 

LUMAKRAS^® (sotorasib) Important U.S. Safety Information 

Hepatotoxicity 

• LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
• Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity.
• Monitor liver function tests (ALT, AST and total bilirubin) prior to the start of LUMAKRAS every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations.
• Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.

Interstitial Lung Disease (ILD)/Pneumonitis 

• LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients.
• Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified.

Most Common Adverse Reactions 

• The most common adverse reactions occurring in ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough.

Drug Interactions 

• Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products.
• Inform patients to avoid proton pump inhibitors and H₂ receptor antagonists while taking LUMAKRAS.
• If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid.

Please see LUMAKRAS full Prescribing Information. 

About Amgen 
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. 

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential. 

Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2023, Amgen was named one of "America's Greatest Workplaces" by Newsweek, one of "America's Climate Leaders" by USA Today and one of the "World's Best Companies" by TIME.

For more information, visit Amgen.com and follow us on X (formerly known as Twitter), LinkedIn, Instagram, TikTok, YouTube and Threads.

Amgen Forward-Looking Statements
This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa-Kirin Co., Ltd.), the performance of Otezla^® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), the Teneobio, Inc. acquisition, the ChemoCentryx, Inc. acquisition, or the Horizon Therapeutics plc acquisition (including the prospective performance and outlook of Horizon's business, performance and opportunities and any potential strategic benefits, synergies or opportunities expected as a result of such acquisition), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market.

Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such acquisition or integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.

The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates. Further, any scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses.

CONTACT: Amgen, Thousand Oaks
Elissa Snook, 609-251-1407 (media)
Jessica Akopyan, 805-440-5721 (media)
Justin Claeys, 805-313-9775 (investors) 

^{__________________________________
1} Sung H, et al. CA Cancer J Clin. 2021;71:209-249.
² Arbour KC, et al. Clin Cancer Res. 2018;24:334-340.
³ Nassar AF, et al. N Engl J. Med. 2021;384:185-187.

 

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SOURCE Amgen

FAQ

What is the latest update from Amgen (AMGN) regarding LUMAKRAS (sotorasib) and the FDA?

Amgen (AMGN) has received a Complete Response Letter from the FDA for the supplemental New Drug Application seeking full approval of LUMAKRAS (sotorasib) based on the CodeBreaK 200 trial results for the treatment of adults with previously treated locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC). The FDA has also issued a new postmarketing requirement for an additional confirmatory study to support full approval.

What is the confirmed dosing for LUMAKRAS for patients with KRAS G12C-mutated NSCLC?

The FDA has confirmed that LUMAKRAS at 960 mg once-daily will remain the dose for patients with KRAS G12C-mutated NSCLC under accelerated approval.

When was LUMAKRAS first approved and how many patients have received it to date?

LUMAKRAS was first approved in May 2021 as the first KRASG12C inhibitor to receive regulatory approval in the U.S. To date, over 15,000 patients worldwide have received LUMAKRAS/LUMYKRAS through the clinical development program, early access, and commercial use.