Press Release Details

THOUSAND OAKS, Calif., Jan. 15, 2015 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced new data from the Phase 2 PEAK and Phase 3 PRIME studies that support the first-line use of Vectibix^® (panitumumab) in combination with FOLFOX, an oxaliplatin-based chemotherapy regimen, in patients with wild-type RAS (absence of exons 2, 3, or 4 KRAS or NRAS mutations) metastatic colorectal cancer (mCRC). The data will be presented during a poster session at the 2015 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium taking place in San Francisco from January 15 to 17.

In an exploratory analysis from the PEAK study (abstract #660), treatment with Vectibix compared to bevacizumab (Avastin^®) resulted in a significantly higher proportion of patients with earlier tumor shrinkage at week eight (64 percent vs. 45 percent, respectively; 95 percent CI, p=0.0232), and among responding patients, a significantly longer duration of response (11.4 vs. 8.5 months, respectively; 95 percent CI, p=0.0142) and greater depth of response (65 percent vs. 46 percent, respectively; p=0.0007). Overall response rates (ORR) appeared to be similar between Vectibix and bevacizumab. This is consistent with observed overall survival (OS) and progression-free survival (PFS) rates, and with data previously reported. The safety profile of Vectibix was consistent with previously reported studies.

"These analyses help deepen our understanding of how Vectibix works when added to a standard first-line chemotherapy for the treatment of wild-type RAS metastatic colorectal cancer," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Our Vectibix clinical trial program continues to yield new insights regarding biomarkers and drug sequencing."

While the primary analysis from PEAK showed similar ORR between the Vectibix- and bevacizumab-based regimens, this exploratory analysis demonstrates that Vectibix produces early, sustained anti-tumor activity, which may in part explain the OS and PFS benefits seen with Vectibix versus bevacizumab in this trial.

A separate analysis from the Phase 3 PRIME study (abstract #537), demonstrated that there were no significant differences in quality of life among patients treated with Vectibix plus FOLFOX versus FOLFOX alone despite the incidence of adverse events associated with each treatment regimen. The quality of life analysis included a scale that assessed mobility, self-care, usual activities, pain/discomfort and anxiety/depression.

Colorectal cancer is the third most common cancer found in both men and women in the U.S. and is the second leading cause of cancer deaths.^1,2 Approximately 1.2 million cases of colorectal cancer are expected to occur globally each year.³

About the PEAK Study
The PEAK (Panitumumab Efficacy in Combination with mFOLFOX6 Against bevacizumab plus mFOLFOX6 in mCRC subjects with wild-type KRAS tumors) ('509) study is a global, multicenter, randomized, interventional Phase 2 trial designed to compare efficacy of first-line Vectibix (panitumumab) in combination with mFOLFOX6 versus bevacizumab in combination with mFOLFOX6 in 285 previously untreated patients with wild-type KRAS exon 2 metastatic colorectal cancer (mCRC). Primary endpoints include progression-free survival (PFS), and secondary endpoints include overall survival (OS), percentage of patients with objective response (OR), duration of response (DoR), depth of response (DpR) and safety.

Patients were randomized in a 1:1 ratio to receive 6 mg/kg of intravenous panitumumab and mFOLFOX6, or 5 mg/kg of intravenous bevacizumab and mFOLFOX6 every 14 days.

In the exploratory analyses of tumor assessments, DpR was defined as the percentage of tumor shrinkage at nadir (point in time between chemotherapy cycles in which a patient experiences low blood counts) or progression. Early tumor shrinkage (ETS) was defined as the proportion of patients with >30 percent tumor shrinkage at week eight.      

About the PRIME Study
The PRIME (Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy) ('203) study is a global, multicenter, randomized Phase 3 study designed to evaluate Vectibix (panitumumab) in combination with FOLFOX versus FOLFOX alone in 1,183 patients with wild-type KRAS exon 2 metastatic colorectal cancer (mCRC). Primary endpoints include progression-free survival (PFS), and secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DoR) and safety.

Patients were randomized in a 1:1 ratio to receive 6 mg/kg of panitumumab (day 1) and FOLFOX (day 1 and 2), or FOLFOX (day 1 and 2) alone of each 14-day cycle.

In this analysis, quality of life (QoL) was assessed every four weeks until disease progression, and once at a safety follow-up, using the EuroQoL 5-domain health state index and overall health rating (OHR; 0-100 visual analogue scale).

About Vectibix^® (panitumumab)
Vectibix is the first fully human anti-EGFR antibody approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic colorectal cancer (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 for patients with wild-type KRAS mCRC.

Important U.S. Product Information
Vectibix is indicated for the treatment of patients with wild-type KRAS (exon 2 in codons 12 or 13) mCRC as determined by an FDA-approved test for this use:

• As first-line therapy in combination with FOLFOX
• As monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy

Vectibix is not indicated for the treatment of patients with KRAS-mutant mCRC or for whom KRAS mutation status is unknown. Vectibix in combination with oxaliplatin-based chemotherapy is not indicated for the treatment of patients with RAS-mutant mCRC or for whom RAS mutation status is unknown.

RAS is defined as 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 hereon is referred to as "RAS."

WARNING: DERMATOLOGIC TOXICITY
Dermatologic Toxicity: Dermatologic toxicities occurred in 90 percent of patients and were severe (NCI-CTC grade 3 or higher) in 15 percent of patients receiving Vectibix monotherapy. [See Dosage and Administration (2.1), Warnings and Precautions (5.1), and Adverse Reactions (6.1)]

A predefined retrospective subset analysis of a clinical study further identified a shortening of progression-free survival (PFS) and overall survival (OS) in patients with RAS-mutant tumors who received Vectibix and FOLFOX versus FOLFOX alone. Determination of RAS-mutant tumor status should be performed by an experienced laboratory.

Determination of KRAS mutational status in colorectal tumors using an FDA-approved test indicated for this use is necessary for selection of patients for treatment with Vectibix.  Patients with KRAS-mutant mCRC tumors receiving Vectibix in combination with FOLFOX experienced shorter OS compared to FOLFOX alone.

Progressively decreasing serum magnesium levels leading to severe (Grade 3-4) hypomagnesemia occurred in up to 7% 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.

In a clinical trial, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grade 3-4).

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 non-fatal 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.

The most common adverse reactions of Vectibix are skin rash with variable presentations, paronychia, fatigue, nausea and diarrhea. The most frequently reported serious, adverse reactions of Vectibix are general physical health deterioration, and intestinal obstruction.

The most commonly reported adverse reactions of Vectibix in combination with FOLFOX are diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. The most frequently reported serious adverse reactions are diarrhea and dehydration.

To see the full Vectibix Safety Information, visit www.vectibix.com.

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 biologics manufacturing 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.

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 Inc. and its subsidiaries (Amgen, we or us) and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including 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 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 (SEC) reports filed by Amgen Inc., including Amgen Inc.'s most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and Form 8-K. Please refer to Amgen Inc.'s most recent Forms 10-K, 10-Q and 8-K for additional information on the uncertainties and risk factors related to our business. Unless otherwise noted, Amgen is providing this information as of Jan. 15, 2015, and expressly disclaims any duty to update information contained in this news release.

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Avastin^® is a registered trademark of Genentech, Inc.

CONTACT: Amgen
Kristen Davis, 805-447-3008 (media)
Cuyler Mayer, 805-447-6332 (media)
Arvind Sood, 805-447-1060 (investors)

References

¹    Colorectal Cancer Facts and Figures. American Cancer Society website. http://www.cancer.org/cancer/colonandrectumcancer/detailedguide/colorectal-cancer-key-statistics. Accessed December 23, 2014.
²    Colorectal Cancer Prevention (PDQ^®). National Cancer Institute website.    http://www.cancer.gov/cancertopics/pdq/prevention/colorectal/HealthProfessional/page3. Accessed December 23, 2014.
³   Jemal. Global Cancer Statistics. CA Cancer J Clin. 2011;61:69-90.

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