Full Press Release Details
THOUSAND OAKS, Calif. , May 18, 2016 /PRNewswire/ -- Amgen (NASDAQ: AMGN ) today announced that new clinical data from across the oncology portfolio, including Kyprolis ® (carfilzomib), IMLYGIC ® (talimogene laherparepvec), Vectibix ® (panitumumab) and Neulasta ® (pegfilgrastim) will be presented at the 52 nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago , June 3-7, 2016 .
"As a leader in patient-focused oncology research, Amgen is committed to translating innovative science into treatments that make a difference in the lives of people suffering from cancer," said Sean E. Harper , M.D., executive vice president of Research and Development at Amgen. "The breadth and depth of data we're presenting at ASCO demonstrates our commitment to finding solutions to some of the toughest cancers. We are thankful for our research partners who help us achieve this mission, and we look forward to sharing these results at ASCO."
Amongst the Kyprolis abstracts to be presented at the meeting will be a new subgroup analysis from the Phase 3 ASPIRE trial which compared Kyprolis in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in relapsed multiple myeloma patients who had early disease progression following prior therapy (including transplant).
Presentations highlighting Kyprolis data include:
Two abstracts on the MASTERKEY-265 trial of IMLYGIC in combination with pembrolizumab in patients with unresectable Stage IIIB-IV melanoma will be presented:
Key data from two abstracts and one publication will be presented on Vectibix, including the final results from a Phase 3 trial of Vectibix and best supportive care (BSC) versus BSC in chemorefractory wild-type KRAS exon 2 and wild-type RAS metastatic colorectal cancer ( mCRC):
Three abstracts will be presented on Neulasta and NEUPOGEN ® (filgrastim), providing new insights into their role in supportive care, including:
One abstract will be presented on investigational agent ABP 215, which is being developed as a biosimilar to bevacizumab:
Abstracts are currently available on the ASCO website.
About Kyprolis ® (carfilzomib) Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed. 1 Kyprolis has been shown to block proteasomes, leading to an excessive build-up of proteins within cells. 2 In some cells, Kyprolis can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins. 2 The irreversibility of Kyprolis' binding has also been shown to offer a more sustained inhibition of the targeted enzymes. 3
Kyprolis is approved in the U.S. for the following:
Kyprolis is also approved in Argentina , Israel , Kuwait , Mexico , Thailand , Colombia , Korea, Canada and the European Union. Additional regulatory applications for Kyprolis are underway and have been submitted to health authorities worldwide.
Kyprolis is a product of Onyx Pharmaceuticals, Inc. Onyx Pharmaceuticals is a subsidiary of Amgen and holds development and commercialization rights to Kyprolis globally, excluding Japan .
For more information, please visit www.kyprolis.com .
Important Safety Information Regarding Kyprolis ® (carfilzomib) for Injection
IMPORTANT SAFETY INFORMATION
Cardiac Toxicities
Acute Renal Failure
Tumor Lysis Syndrome
Pulmonary Toxicity
Pulmonary Hypertension
Venous Thrombosis
Infusion Reactions
Thrombocytopenia
Hepatic Toxicity and Hepatic Failure
Thrombotic Microangiopathy
Posterior Reversible Encephalopathy Syndrome (PRES)
Embryo-fetal Toxicity
ADVERSE REACTIONS
Please see full Prescribing Information at www.kyprolis.com .
About IMLYGIC™ (talimogene laherparepvec) IMLYGIC is a genetically modified herpes simplex type 1 virus that is injected directly into tumors. IMLYGIC replicates inside tumor cells and produces GM-CSF, an immunostimulatory protein. IMLYGIC then causes the cell to rupture and die in a process called lysis. The rupture of the cancer cells causes the release of tumor-derived antigens, which together with virally derived GM-CSF may help to promote an anti-tumor immune response. However, the exact mechanism of action is unknown.
IMLYGIC is the first oncolytic viral therapy approved by the U.S. Food and Drug Administration (FDA) based on therapeutic benefit demonstrated in a pivotal study. IMLYGIC is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. IMLYGIC has not been shown to improve overall survival or have an effect on visceral metastases.
Important Safety Information
Contraindications
Warnings and Precautions
Adverse Reactions
Please see full Prescribing Information and Medication Guide for IMLYGIC™ at www.IMLYGIC.com .
About Vectibix ® (panitumumab) Vectibix is the first fully human monoclonal anti-epidermal growth factor receptor (EGFR) antibody approved by the 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) metastatic colorectal cancer (mCRC) as determined by an FDA-approved test for this use:
Limitation of Use: Vectibix ® is not indicated for the treatment of patients with RAS -mutant mCRC or for whom RAS mutation status is unknown.
WARNING: DERMATOLOGIC TOXICITY Dermatologic Toxicity: Dermatologic toxicities occurred in 90 percent of patients and were severe (NCI-CTC grade 3 or higher) in 15% of patients receiving Vectibix monotherapy.
In Study 1, 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 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 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 3, 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 2) 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 1, 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 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.
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.
Advise patients of the need for adequate contraception in both males and females while receiving Vectibix ® and for 6 months after the last dose of Vectibix ® therapy. Vectibix ® may be transmitted from the mother to the developing fetus, and has the potential to cause fetal harm when administered to pregnant women.
Women who become pregnant during Vectibix ® treatment are encouraged to enroll in Amgen's Pregnancy Surveillance Program. Women who are nursing during Vectibix ® treatment are encouraged to enroll in Amgen's Lactation Surveillance Program. Patients or their physicians should call 1-800-77-AMGEN (1-800-772-6436) to enroll.
In Study 1, the most common adverse reactions ( > 20%) with Vectibix ® were skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea. The most common (> 5%) serious adverse reactions in the Vectibix ® arm were general physical health deterioration and intestinal obstruction.
In Study 3, the most commonly reported adverse reactions (> 20%) in patients with wild-type KRAS mCRC receiving Vectibix ® (6 mg/kg every 2 weeks) and FOLFOX therapy (N = 322) were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus and dry skin. Serious adverse reactions (> 2% difference between treatment arms) in Vectibix ® -treated patients with wild-type KRAS mCRC were diarrhea and dehydration.
To see the Vectibix ® Prescribing Information, including Boxed Warning visit www.vectibix.com .
In the EU, Vectibix is currently indicated for the treatment of adult patients with wild-type RAS mCRC:
About Neulasta ® (pegfilgrastim) Neulasta is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. Neulasta is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.
In a pivotal clinical trial, in patients with nonmyeloid malignancies undergoing myelosuppressive chemotherapy associated with a clinically significant incidence of febrile neutropenia, treatment with Neulasta was shown to significantly reduce the incidence of febrile neutropenia..
Neulasta is administered by manual injection and is also available via the Neulasta ® Onpro TM kit, which was approved by the FDA in 2014 and includes a specially designed, single-use prefilled syringe co-packaged with an on-body injector for Neulasta. For more information about Neulasta, visit www.Neulasta.com and www.NeulastaHCP.com .
Important Safety Information Regarding Neulasta ®
Contraindication Do not administer Neulasta ® to patients with a history of serious allergic reactions to pegfilgrastim or filgrastim.
Splenic Rupture Splenic rupture, including fatal cases, can occur following the administration of Neulasta ® . Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after receiving Neulasta ® .
Acute Respiratory Distress Syndrome Acute respiratory distress syndrome (ARDS) can occur in patients receiving Neulasta ® . Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving Neulasta for ARDS. Discontinue Neulasta ® in patients with ARDS.
Serious Allergic Reactions
Serious allergic reactions, including anaphylaxis, can occur in patients receiving Neulasta ® . The majority of reported events occurred upon initial exposure. Allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue Neulasta ® in patients with serious allergic reactions.
Allergies to Acrylics The on-body injector for Neulasta ® uses acrylic adhesive. For patients who have reactions to acrylic adhesives, use of this product may result in a significant reaction.
Use in Patients with Sickle Cell Disorders Severe sickle cell crises can occur in patients with sickle cell disorders receiving Neulasta ® . Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving filgrastim, the parent compound of pegfilgrastim.
Glomerulonephritis Glomerulonephritis has been reported in patients receiving Neulasta®. The diagnoses were based upon azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Generally, events of glomerulonephritis resolved after withdrawal of Neulasta®. If glomerulonephritis is suspected, evaluate for cause. If causality is likely, consider dose‐reduction or interruption of Neulasta ® .
Leukocytosis White blood cell counts of 100 x 109/L or greater have been observed in patients receiving pegfilgrastim. Monitoring of CBCs during pegfilgrastim therapy is recommended.
Capillary Leak Syndrome Capillary leak syndrome has been reported after granulocyte colony‐stimulating factor (G‐CSF) administration, including Neulasta ® , and is characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration. Episodes vary in frequency, severity and may be life‐threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care.
Potential for Tumor Growth Stimulatory Effects on Malignant Cells The granulocyte colony-stimulating factor (G-CSF) receptor, through which pegfilgrastim and filgrastim act, has been found on tumor cell lines. The possibility that pegfilgrastim acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim is not approved, cannot be excluded.
The most common adverse reactions (≥ 5% difference in incidence) in placebo-controlled clinical trials are bone pain and pain in extremity.
Please see additional Neulasta ® Safety Information, by visiting www.amgen.com/medpro/products.html .
Please see the Neulasta Full Prescribing Information by clicking here.