We aspire to be the best human therapeutics company. Achieving our goal starts with building the best R&D organization. Our R&D is led by dedicated, creative scientists who are attracted to Amgen by our intellectual vigor, our commitment to world-class research, and most importantly, by the many opportunities we offer to make a dramatic difference in the lives of patients. Four principles guide our R&D efforts.
The first is to focus on developing therapies that benefit patients with the greatest unmet medical needs.
The second is to be modality independent—to fit the tool to the task. We are not driven to work in a disease area by our drug development capabilities. For us, the question is always: What’s the best therapeutic approach for a particular disease?
Our third major emphasis is to study disease in patients. All too often, our industry has found that experimental models have little predictive value with respect to human disease, which often results in the failure of clinical trials and escalating drug-development costs.
Our fourth guiding principle, seamless integration, informs everything we do. We strive to integrate our organization, incorporating perspectives from sales and marketing, clinical development and basic research into all of our drug-development programs.
These four guiding principles, together with hard work, intelligence, intuition, and some luck, will help us achieve our aspiration to become the best human therapeutics company.
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Vectibix® is indicated as a single agent for the treatment of EGFR-expressing, metastatic colorectal carcinoma (mCRC) with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
The effectiveness of Vectibix® as a single agent for the treatment of EGFR-expressing mCRC is based on progression-free survival. Currently no data are available that demonstrate an improvement in disease related symptoms or increased survival with Vectibix®.
Important Safety Information
Safety data are available from 15 clinical trials in which 1,467 patients received Vectibix®; of these, 1,293 received Vectibix® monotherapy and 174 received Vectibix® in combination with chemotherapy.
WARNING Infusion Reactions: Severe infusion reactions occurred with the administration of Vectibix® in approximately 1% of patients. Severe infusion reactions were identified by reports of anaphylactic reaction, bronchospasm, fever, chills, and hypotension. Although fatal infusion reactions have not been reported with Vectibix®, fatalities have occurred with other monoclonal antibody products. Stop infusion if a severe infusion reaction occurs. Depending on the severity and/or persistence of the reaction, permanently discontinue Vectibix®.
Dermatologic Toxicity:Dermatologic toxicities, related to Vectibix® blockade of EGF binding and subsequent inhibition of EGFR-mediated signaling pathways, were reported in 89% of patients and were severe (NCI-CTC grade 3 and higher) in 12% of patients receiving Vectibix® monotherapy. The clinical manifestations included, but were not limited to, dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures. Severe dermatologic toxicities were complicated by infection including sepsis, septic death, and abscesses requiring incisions and drainage. Withhold or discontinue Vectibix® and monitor for inflammatory or infectious sequelae in patients with severe dermatologic toxicities.
Vectibix® is not indicated for use in combination with chemotherapy with or without bevacizumab. In an interim analysis of a randomized (1:1) clinical trial of patients with previously untreated metastatic colorectal cancer, the addition of Vectibix® to the combination of bevacizumab and chemotherapy resulted in decreased progression-free survival (n=947) and increased incidence of NCI-CTC grade 3-5 (87% vs. 72%) adverse reactions (n=926).
In a single-arm study of 19 patients receiving Vectibix® in combination with IFL, the incidence of NCI-CTC grade 3-4 diarrhea was 58%; in addition, grade 5 diarrhea occurred in 1 patient. In a single-arm study of 24 patients receiving Vectibix® plus FOLFIRI, the incidence of NCI-CTC grade 3 diarrhea was 25%.
Pulmonary fibrosis occurred in less than 1% (2/1,467) of patients in clinical trials of Vectibix®. Following the initial fatality, patients with a history of interstitial pneumonitis, pulmonary fibrosis, and evidence of interstitial pneumonitis were excluded from clinical studies. Therefore, the estimated risk in such patients is uncertain. Permanently discontinue Vectibix® therapy in patients developing interstitial lung disease, pneumonitis, or lung infiltrates.
In the randomized, controlled clinical trial, median magnesium levels decreased by 0.1 mmol/L in the Vectibix® arm. Additionally, hypomagnesemia (NCI-CTC grade 3 or 4) requiring electrolyte repletion occurred in 2% of patients 6 weeks or longer after the initiation of Vectibix®. In some patients, hypomagnesemia was associated with hypocalcemia. Patients should be periodically monitored, and treated appropriately, for hypomagnesemia and hypocalcemia during and for 8 weeks after the completion of Vectibix® therapy.
It is recommended that patients wear sunscreen and hats and limit sun exposure while receiving Vectibix®, since sunlight can exacerbate any skin reactions that may occur.
In women of childbearing potential, appropriate contraceptive measures must be used during, and for 6 months after, treatment with Vectibix®.
The most common adverse events observed in clinical studies of Vectibix® (n = 1,467) were skin rash with variable presentations, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea, and diarrhea, including diarrhea resulting in dehydration. The most serious adverse events observed were pulmonary fibrosis, severe dermatologic toxicity complicated by infectious sequelae and septic death, infusion reactions, abdominal pain, hypomagnesemia, nausea, vomiting, and constipation.
