First Prospective Study of Treatment in Patients with Wild-Type

RAS

Colorectal Cancer and Left-Sided Primary Tumor

Results From the Phase 3 PARADIGM Trial Being Featured During ASCO 2022 Plenary Session

THOUSAND OAKS, Calif.

and

OSAKA, Japan


,


June 5, 2022


/PRNewswire/ — Amgen (NASDAQ:AMGN) and Takeda Pharmaceutical Company (TSE: 4502) today announced that new data from the Phase 3 PARADIGM clinical trial of Vectibix

^®

(panitumumab) in Japanese patients with previously untreated unresectable wild-type

RAS

metastatic colorectal cancer (mCRC) are being featured during the

June 5

Plenary Session (Abstract #LBA1) of the American Society of Clinical Oncology (ASCO) Annual Meeting being held in

Chicago

and online.

PARADIGM is a randomized trial conducted in

Japan

comparing the efficacy and safety of Vectibix plus mFOLFOX6 compared to bevacizumab plus mFOLFOX6 in chemotherapy-naive patients with unresectable advanced mCRC (n=823). This trial was conducted by Takeda. This is the first prospective trial to evaluate treatment options for patients with wild-type

RAS

mCRC and left-side primary tumor (descending colon, sigmoid colon, and rectum).

“Data from the PARADIGM study demonstrate the superiority of Vectibix over bevacizumab, both with chemotherapy, further establishing this Vectibix combination regimen as a standard of care for first-line treatment of wild-type

RAS

metastatic colorectal cancer,” said

David M. Reese

, M.D., executive vice president of Research and Development at Amgen. “These study results build on the long history of Vectibix in the treatment of advanced colorectal cancer and reinforce the importance of comprehensive biomarker testing to identify all eligible patients.”

The results of the trial showed that the mFOLFOX6 + Vectibix combination provides a statistically significant improvement in overall survival (OS) over the mFOLFOX6 + bevacizumab combination in patients with a left-sided primary tumor or regardless of tumor locations (median OS for left-sided tumors: 37.9 vs. 34.3 months, HR=0.82 [95.798% CI: 0.68-0.99], p=0.031, overall median OS: 36.2 vs. 31.3 months, HR=0.84 [95% CI: 0.72-0.98], p=0.030). The safety profile of Vectibix in this study was similar to clinical study results previously published.

“This is the first prospective Phase 3 study of treatment in patients with wild-type

RAS,

unresectable metastatic colorectal cancer and left-sided primary tumor,” said Dr.

Takayuki Yoshino

, chief for the Department of Gastrointestinal Oncology, and deputy director at the National Cancer Center Hospital East. “These results provide further evidence of the benefits Vectibix provides for treatment in wild-type

RAS

, left-sided mCRC.”

“These results further our understanding of the value Vectibix plus chemotherapy as a first-line treatment may provide for this patient population,” said

Takafumi Horii

, head of the Japan Oncology BU, Global Oncology Unit at Takeda Pharmaceutical. “We are grateful to the patients, families and physicians in

Japan

who have contributed to this trial as we strive to deliver new therapeutic options for patients with unmet needs around the world.”

For more detailed results of the study, please refer to

ASCO.org

.

The PARADIGM Trial

About Vectibix

^®

(panitumumab)

Vectibix is the first fully human monoclonal anti-EGFR antibody approved by the FDA for the treatment of mCRC. Vectibix was approved in the U.S. in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.

In May 2014, the FDA approved Vectibix for use in combination with FOLFOX, as first-line treatment in patients with wild-type

KRAS

(exon 2) mCRC. With this approval, Vectibix became the first-and-only biologic therapy indicated for use with FOLFOX, one of the most commonly used chemotherapy regimens, in the first-line treatment of mCRC specifically for patients with wild-type

KRAS

mCRC.

In June 2017, the FDA approved a refined indication for Vectibix for use in in patients with wild-type

RAS

(defined as wild-type in both

KRAS

and

NRAS

as determined by an FDA-approved test for this use

)

mCRC.

INDICATION AND LIMITATION OF USE

Vectibix

^®

is indicated for the treatment of patients with wild-type

RAS

(defined as wild-type in both

KRAS

and

NRAS

as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC): as first-line therapy in combination with FOLFOX, and as monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.

Limitation of Use: Vectibix

^®

is not indicated for the treatment of patients with

RAS

mutant mCRC or for whom

RAS

mutation status is unknown.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: DERMATOLOGIC TOXICITY

Dermatologic Toxicity:

Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients receiving Vectibix monotherapy

[see Dosage and Administration (2.3), Warnings and Precautions (5.1), and Adverse Reactions (6.1)].

• In Study 20020408, dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients with mCRC receiving Vectibix
  
  ^®
  
  . The clinical manifestations included, but were not limited to, acneiform dermatitis, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures.
• Monitor patients who develop dermatologic or soft tissue toxicities while receiving Vectibix
  
  ^®
  
  for the development of inflammatory or infectious sequelae. Life-threatening and fatal infectious complications including necrotizing fasciitis, abscesses, and sepsis have been observed in patients treated with Vectibix
  
  ^®
  
  . Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has also been observed in patients treated with Vectibix
  
  ^®
  
  . It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune- related effects (e.g., Stevens Johnson syndrome or toxic epidermal necrolysis). Withhold or discontinue Vectibix
  
  ^®
  
  for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications. Dose modifications for Vectibix
  
  ^®
  
  concerning dermatologic toxicity are provided in the product labeling.
• Vectibix
  
  ^®
  
  is not indicated for the treatment of patients with colorectal cancer that harbor somatic
  
  RAS
  
  mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either
  
  KRAS
  
  or
  
  NRAS
  
  and hereafter is referred to as ”
  
  RAS.
  
  ”
• Retrospective subset analyses across several randomized clinical trials were conducted to investigate the role of
  
  RAS
  
  mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies (panitumumab or cetuximab). Anti-EGFR antibodies in patients with tumors containing
  
  RAS
  
  mutations resulted in exposing those patients to anti-EGFR related adverse reactions without clinical benefit from these agents. Additionally, in Study 20050203, 272 patients with
  
  RAS
  
  -mutant mCRC tumors received Vectibix
  
  ^®
  
  in combination with FOLFOX and 276 patients received FOLFOX alone. In an exploratory subgroup analysis
  
  ,
  
  OS was shorter (HR = 1.21, 95% CI: 1.01-1.45) in patients with
  
  RAS
  
  -mutant mCRC who received Vectibix
  
  ^®
  
  and FOLFOX versus FOLFOX alone.
• Progressively decreasing serum magnesium levels leading to severe (grade 3-4) hypomagnesemia occurred in up to 7% (in Study 20080763) of patients across clinical trials. Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix
  
  ^®
  
  treatment, periodically during Vectibix
  
  ^®
  
  treatment, and for up to 8 weeks after the completion of treatment. Other electrolyte disturbances, including hypokalemia, have also been observed. Replete magnesium and other electrolytes as appropriate.
• In Study 20020408, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grade 3-4). Infusion reactions, manifesting as fever, chills, dyspnea, bronchospasm, and hypotension, can occur following Vectibix
  
  ^®
  
  administration. Fatal infusion reactions occurred in postmarketing experience. Terminate the infusion for severe infusion reactions.
• Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix
  
  ^®
  
  in combination with chemotherapy.
• Fatal and nonfatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix
  
  ^®
  
  . Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix
  
  ^®
  
  . In the event of acute onset or worsening of pulmonary symptoms interrupt Vectibix
  
  ^®
  
  therapy. Discontinue Vectibix
  
  ^®
  
  therapy if ILD is confirmed.
• In patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis, the benefits of therapy with Vectibix
  
  ^®
  
  versus the risk of pulmonary complications must be carefully considered.
• Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix
  
  ^®
  
  .
• Keratitis and ulcerative keratitis, known risk factors for corneal perforation, have been reported with Vectibix
  
  ^®
  
  use. Monitor for evidence of keratitis or ulcerative keratitis. Interrupt or discontinue Vectibix
  
  ^®
  
  for acute or worsening keratitis.
• In an interim analysis of an open-label, multicenter, randomized clinical trial in the first-line setting in patients with mCRC, the addition of Vectibix
  
  ^®
  
  to the combination of bevacizumab and chemotherapy resulted in decreased OS and increased incidence of NCI-CTC grade 3-5 (87% vs 72%) adverse reactions. NCI-CTC grade 3-4 adverse reactions occurring at a higher rate in Vectibix
  
  ^®
  
  -treated patients included rash/acneiform dermatitis (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs < 1%), and hypomagnesemia (4% vs 0).
• NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix
  
  ^®
  
  -treated patients (7% vs 3%) and included fatal events in three (< 1%) Vectibix
  
  ^®
  
  -treated patients. As a result of the toxicities experienced, patients randomized to Vectibix
  
  ^®
  
  , bevacizumab, and chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-FU, and/or infusional 5-FU) over the first 24 weeks on study compared with those randomized to bevacizumab and chemotherapy.
• Vectibix
  
  ^®
  
  can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment, and for at least 2 months after the last dose of Vectibix
  
  ^®
  
  .
• In monotherapy, the most commonly reported adverse reactions (≥ 20%) in patients with Vectibix
  
  ^®
  
  were skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea.
• The most commonly reported adverse reactions (≥ 20%) with Vectibix
  
  ^®
  
  + FOLFOX were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. The most common serious adverse reactions (≥ 2% difference between treatment arms) were diarrhea and dehydration.

To see the Vectibix

^®

Prescribing Information, including Boxed Warning visit

www.vectibix.com

.

About Colorectal Cancer

Colorectal cancer is the second most common cancer in women worldwide and the third most common cancer in men. Approximately 1.2 million cases of colorectal cancer are expected to occur globally. With more than 630,000 deaths worldwide per year, it is the third leading cause of cancer-related death in the Western world. The highest incidence rates are found in Japan, North America, parts of Europe, New Zealand, and Australia, and rates are low in Africa and Southeast Asia.[1] Using molecular approaches to identify unique genetic signatures in mCRC has the potential to help improve treatment outcomes.[2]

About Amgen Oncology

At Amgen Oncology, our mission to serve patients drives all that we do. That’s why we’re relentlessly focused on accelerating the delivery of medicines that have the potential to empower all angles of care and transform lives of people with cancer.

For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company’s history, moving with great speed to advance those innovations for the patients who need them.

For more information, follow us on

www.twitter.com/amgenoncology

.

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 2021, Amgen was named one of the 25 World’s Best Workplaces™ by Fortune and Great Place to Work™ and one of the 100 most sustainable companies in the world by

Barron’s

.

For more information, visit

www.amgen.com

and follow us on

www.twitter.com/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., Kyowa-Kirin Co., Ltd., or any collaboration to manufacture therapeutic antibodies against COVID-19), the performance of Otezla

^®

(apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), the Five Prime Therapeutics, Inc. acquisition, or the Teneobio, Inc. 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 such as the ongoing COVID-19 pandemic on our business, 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. A breakdown, cyberattack or information security breach 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.

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CONTACT:

Amgen, Thousand Oaks


Megan Fox

, 805-447-1423 (media)


Jessica Akopyan

, 805-440-5721 (media)


Arvind Sood

, 805-447-1060 (investors)

¹

Jemal A, et al. Global Cancer Statistics. CA

CANCER J CLIN

2011;61:69-90.

²

Fight Colorectal Cancer. Biomarker Fact Sheet. Available at:

https://fightcolorectalcancer.org/fight/diagnosis/

. Accessed

May 9, 2022

.

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