Full Press Release Details
THOUSAND OAKS, Calif. , June 21, 2017 /PRNewswire/ -- Amgen (NASDAQ: AMGN ) today announced that new clinical data and analyses from its hematology portfolio will be presented at the 22 nd Congress of the European Hematology Association (EHA) in Madrid, June 22-25, 2017. Key data will be presented from studies evaluating KYPROLIS ® (carfilzomib), BLINCYTO ® (blinatumomab), XGEVA ® (denosumab) and Nplate ® (romiplostim).
"Helping patients live longer is the ultimate goal of all of our oncology therapeutic research and development," said Sean E. Harper , M.D., executive vice president of Research and Development at Amgen. "The KYPROLIS and BLINCYTO overall survival data at EHA are impressive and give us confidence that we are making significant progress finding effective new therapies for these difficult-to-treat cancers."
KYPROLIS ® is the first-and-only multiple myeloma therapy to demonstrate superior overall survival in a head-to-head comparison with a current standard of care, extending survival by 7.6 months over Velcade ® (bortezomib). 1 These results from the ENDEAVOR trial will be featured in an oral presentation at EHA.
A new analysis will be presented from the Phase 3 TOWER study, which demonstrated that in adult patients treated with no prior salvage therapy, BLINCYTO more than doubled median overall survival compared to standard of care chemotherapy in Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). These data come from a subgroup analysis, and TOWER was not powered to assess overall survival efficacy in this subgroup.
New XGEVA data will be presented during an oral session, highlighting results from a post-hoc, 15-month landmark analysis of the Phase 3 '482 study, the largest international multiple myeloma trial ever conducted. This analysis demonstrated an improved delay in time to first skeletal-related event for the XGEVA treated patients. The study endpoint and the analysis were not powered to determine efficacy.
On June 16 , the U.S. Food and Drug Administration (FDA) accepted for review the XGEVA supplemental Biologics License Application that seeks to expand the currently approved indication for the prevention of skeletal-related events in patients with bone metastases from solid tumors to include patients with multiple myeloma. The Prescription Drug User Fee Act (PDUFA) target action date is Feb. 3, 2018 . Data from the '482 study are also the basis of an application for a variation to the marketing authorization submitted to the European Medicines Agency. Currently, XGEVA is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.
The Nplate abstracts to be presented at EHA include data from an ongoing, open-label extension study evaluating the safety and efficacy of Nplate in children with immune thrombocytopenia (ITP):
Abstracts are currently available on the EHA 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. 2 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. 2,3
KYPROLIS is approved in the U.S. for the following:
KYPROLIS is also approved in Argentina , Australia , Bahrain , Canada , Hong Kong , Israel , Japan , Kuwait , Lebanon , Macao , Mexico , Thailand , Colombia , S. Korea, Canada , Qatar , Switzerland , United Arab Emirates , Turkey , Russia , Brazil , India and the European Union. Additional regulatory applications for KYPROLIS are underway and have been submitted to health authorities worldwide.
For more U.S. information, please visit www.kyprolis.com .
Important EU Product Safety Information
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
Kyprolis treatment should be supervised by a physician experienced in the use of anti-cancer therapy. The most serious side effects that may occur during Kyprolis treatment include: Cardiac toxicity, pulmonary toxicities, pulmonary hypertension, dyspnea, hypertension including hypertensive crises, acute renal failure, tumor lysis syndrome, infusion reactions, thrombocytopenia, hepatic toxicity, posterior reversible encephalopathy syndrome (PRES) and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). The most common side effects are anemia, fatigue, diarrhea, thrombocytopenia, nausea, pyrexia, dyspnea, respiratory tract infection, cough and peripheral edema.
Please refer to the Summary of Product Characteristics for full European prescribing information.
Important U.S. Product 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)
Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant ‐ ineligible Patients
Embryo-fetal Toxicity
ADVERSE REACTIONS
Please see full prescribing information at www.kyprolis.com .
About BLINCYTO ® (blinatumomab) BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE ® ) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.
BLINCYTO was granted breakthrough therapy and priority review designations by the FDA, and is now approved in the U.S. for the treatment of Ph- relapsed or refractory B-cell precursor ALL. This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.
In November 2015 , BLINCYTO was granted conditional marketing authorization in the European Union for the treatment of adults with Ph- relapsed or refractory B-cell precursor ALL.
Important EU BLINCYTO ® (blinatumomab) Safety Information
This product is subject to additional monitoring in the EU. All suspected adverse reactions should be reported in accordance with the national reporting system.
The adverse reactions described in this section were identified in the pivotal clinical study (N=189).The most serious adverse reactions that may occur during blinatumomab treatment include: infections (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%), cytokine release syndrome (0.5%), and tumor lysis syndrome (0.5%). The most common adverse reactions were: infusion-related reactions (67.2%), infections (63.0%), pyrexia (59.8%), headache (34.4%), febrile neutropenia (28%), peripheral edema (25.9%), nausea (24.3%), hypokalaemia (23.8%), constipation (20.6%), anaemia (20.1%), cough (18.5%), diarrhea (18.0%), tremor (17.5%), neutropenia (17.5%), abdominal pain (16.9%), insomnia (15.3%), fatigue (15.3%), and chills (15.3%).
Please refer to the Summary of Product Characteristics for full European prescribing information.
Important Safety Information Regarding BLINCYTO ® (blinatumomab) U.S. Indication
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES
Contraindications BLINCYTO ® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.
Warnings and Precautions
Adverse Reactions
U.S. Dosage and Administration Guidelines
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide, for BLINCYTO ® at www.BLINCYTO.com .
About XGEVA ® (denosumab) XGEVA targets the RANK Ligand pathway to prevent the formation, function and survival of osteoclasts, which break down bone. XGEVA is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors and for treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. XGEVA is also indicated in the U.S. for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. XGEVA is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.
Important EU Product Safety Information
Special Warnings and Precautions: Pre-existing hypocalcaemia must be corrected prior to initiating therapy with XGEVA. Hypocalcaemia can occur at any time during therapy. Monitor calcium prior to initial dose, within two weeks of initial dose and if suspected symptoms of hypocalcaemia occur. Severe symptomatic hypocalcaemia has been reported. Consider additional monitoring of calcium level in patients with risk factors for hypocalcaemia or if otherwise indicated based on clinical condition of the patient. If hypocalcaemia occurs while receiving XGEVA, additional calcium supplementation and additional monitoring may be necessary.
Patients with severe renal impairment (creatinine clearance < 30ml/min) or receiving dialysis are at greater risk of developing hypocalcaemia; this risk and accompanying elevations in parathyroid hormone increases with increasing degree of renal impairment. Regular monitoring of calcium levels in these patients is especially important.
Osteonecrosis of the jaw (ONJ) has occurred commonly in patients treated with XGEVA. Delay treatment in patients with unhealed open soft tissue lesions in the mouth. A dental examination with preventive dentistry and an individual benefit-risk assessment is recommended prior to treatment. Refer to the SmPC for risk factors for ONJ. Patients should be encouraged to maintain good oral hygiene, receive routine dental check-ups and immediately report oral symptoms during treatment with XGEVA. While on treatment, invasive dental procedures should be performed only after careful consideration and avoided in close proximity to XGEVA administration. The management plan of patients who develop ONJ should be set up in close collaboration between the treating physician and a dentist or oral surgeon with expertise in ONJ.
Atypical femoral fracture (AFF) has been reported in patients receiving XGEVA. Discontinuation of XGEVA therapy in patients suspected to have AFF should be considered pending evaluation of the patient based on an individual benefit risk assessment. XGEVA is not recommended in patients with growing skeletons. Clinically significant hypercalcaemia has been reported in XGEVA-treated patients with growing skeletons weeks to months following treatment discontinuation. Patients being treated with XGEVA should not be treated concomitantly with other denosumab containing medicinal products (for osteoporosis indications) or with bisphosphonates. Patients with rare hereditary problems of fructose intolerance should not use XGEVA.
Adverse reactions in patients receiving XGEVA to prevent the occurrence of skeletal related events: very common (≥ 1/10) dyspnea, diarrhea and musculoskeletal pain; common (≥ 1/100 to < 1/10) hypocalcaemia, hypophosphatemia, tooth extraction, hyperhidrosis and osteonecrosis of the jaw; rare (≥ 1/10,000 to < 1/1000) drug hypersensitivity, anaphylactic reaction, atypical femoral fracture. In three phase III clinical trials, ONJ was confirmed in 1.8% of patients treated with XGEVA and 1.3% of patients treated with zoledronic acid (primary treatment phase). Among subjects with confirmed ONJ, most (81% in both treatment groups) had a history of tooth extraction, poor oral hygiene, and/or use of a dental appliance. Hypocalcaemia was reported in 9.6% of patients treated with XGEVA and 5.0% of patients treated with zoledronic acid. Neutralizing antibodies have not been observed in clinical studies. In the postmarketing setting, severe symptomatic hypocalcaemia (including fatal cases), hypersensitivity (including rare events of anaphylactic reaction) and musculoskeletal pain (including severe cases) have been reported. Please consult the SmPC for a full description of undesirable effects.
Contraindications: Severe, untreated hypocalcaemia; hypersensitivity to the active substance or to any of the excipients; unhealed lesions from dental or oral surgery.
U.S. Important Safety Information
Hypocalcemia Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA ® . XGEVA ® can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Monitor calcium levels, especially in the first weeks of initiating therapy, and administer calcium, magnesium, and vitamin D as necessary. Monitor levels more frequently when XGEVA ® is administered with other drugs that can also lower calcium levels. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.
An increased risk of hypocalcemia has been observed in clinical trials of patients with increasing renal dysfunction, most commonly with severe dysfunction (creatinine clearance less than 30 mL/minute and/or on dialysis), and with inadequate/no calcium supplementation. Monitor calcium levels and calcium and vitamin D intake.
Hypersensitivity XGEVA ® is contraindicated in patients with known clinically significant hypersensitivity to XGEVA ® , including anaphylaxis that has been reported with use of XGEVA ® . Reactions may include hypotension, dyspnea, upper airway edema, lip swelling, rash, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue XGEVA ® therapy permanently.
Drug Products with Same Active Ingredient Patients receiving XGEVA ® should not take Prolia ® (denosumab).
Osteonecrosis of the Jaw Osteonecrosis of the jaw (ONJ) has been reported in patients receiving XGEVA ®, manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion. Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ. In clinical trials in patients with osseous metastasis, the incidence of ONJ was higher with longer duration of exposure.
Patients with a history of tooth extraction, poor oral hygiene, or use of a dental appliance are at a greater risk to develop ONJ. Other risk factors for the development of ONJ include immunosuppressive therapy, treatment with angiogenesis inhibitors, systemic corticosteroids, diabetes, and gingival infections.
Perform an oral examination and appropriate preventive dentistry prior to the initiation of XGEVA ® and periodically during XGEVA ® therapy. Advise patients regarding oral hygiene practices. Avoid invasive dental procedures during treatment with XGEVA ® . Consider temporarily interrupting XGEVA ® therapy if an invasive dental procedure must be performed.
Patients who are suspected of having or who develop ONJ while on XGEVA ® should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.
Atypical Subtrochanteric and Diaphyseal Femoral Fracture Atypical femoral fracture has been reported with XGEVA ® . These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution.
Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture. During XGEVA ® treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patients presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of XGEVA ® therapy should be considered, pending a risk/benefit assessment, on an individual basis.
Hypercalcemia Following Treatment Discontinuation in Patients with Growing Skeletons Clinically significant hypercalcemia has been reported in XGEVA ® treated patients with growing skeletons, weeks to months following treatment discontinuation. Monitor patients for signs and symptoms of hypercalcemia and treat appropriately.
Embryo-Fetal Toxicity XGEVA ® can cause fetal harm when administered to a pregnant woman. Based on findings in animals, XGEVA ® is expected to result in adverse reproductive effects. Advise females of reproductive potential to use highly effective contraception during therapy, and for at least 5 months after the last dose of XGEVA ® . Apprise the patient of the potential hazard to a fetus if XGEVA ® is used during pregnancy or if the patient becomes pregnant while patients are exposed to XGEVA ® .
Adverse Reactions The most common adverse reactions in patients receiving XGEVA ® with bone metastasis from solid tumors were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction was dyspnea.
The most common adverse reactions resulting in discontinuation were osteonecrosis and hypocalcemia. The most common adverse reactions in patients receiving XGEVA ® for giant cell tumor of bone were arthralgia, headache, nausea, back pain, fatigue, and pain in extremity. The most common serious adverse reactions were osteonecrosis of the jaw and osteomyelitis. The most common adverse reactions resulting in discontinuation of XGEVA ® were osteonecrosis of the jaw and tooth abscess or tooth infection. The most common adverse reactions in patients receiving XGEVA ® for hypercalcemia of malignancy were nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea.
Denosumab is also marketed as Prolia ® in other indications.
Please visit www.amgen.com or www.xgeva.com for Full U.S. Prescribing Information.
About Nplate ® (romiplostim) Nplate is approved in over 50 countries worldwide, including the U.S., European Union (EU), Canada , Australia , Russia , Mexico , Switzerland , Lichtenstein, Japan , Argentina , Israel , South Korea , Hong Kong , and Chile . Nplate also has received orphan designation for chronic ITP in the U.S. (2003), the EU (2005) and other parts of the world.
Nplate is the first FDA-approved treatment specifically for adult chronic ITP.
In the U.S., Nplate is indicated for the treatment of thrombocytopenia in patients with chronic ITP who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy. Nplate is not indicated for the treatment of thrombocytopenia due to myelodysplastic syndrome (MDS) or any cause of thrombocytopenia other than chronic ITP. Nplate should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. Nplate should not be used in an attempt to normalize platelet counts.
In the EU, Nplate is indicated for adult chronic-immune (idiopathic)-thrombocytopenic-purpura (ITP) patients who are refractory to other treatments (e.g. corticosteroids, immunoglobulins).
Nplate was named as a recipient of the U.S. Prix Galien 2009 "Best Biotechnology Product" award and also received the 2009 Scrip Awards for "Best New Drug." Nplate has also been honored with numerous awards throughout the EU, including a 2010 Prix Galien in France in the category of "Drugs for Rare Diseases," and the 2011 Prix Galien in Germany in the category of "Specialist Care." In September 2010 , Nplate was awarded the 2010 International Prix Galien Award, an award granted every two years which recognizes the "best of the best" selected from previous national Prix Galien award recipients.
For more information about Nplate, please visit www.Nplate.com .
Important EU Nplate ® Safety Information The EU Summary of Product Characteristics for Nplate lists the following Special Warnings and Precautions: Reoccurrence of thrombocytopenia and bleeding after cessation of treatment, increased bone marrow reticulin, thrombotic/thromboembolic complications, progression of existing MDS (in patients with MDS), medication errors, loss of response to Nplate, and effects on red and white blood cells.
The most common adverse reactions observed include hypersensitivity reactions (including cases of rash, urticarial and angioedema) and headache. As with all therapeutic proteins, there is a potential for immunogenicity.
Please refer to the Summary of Product Characteristics for full European prescribing information.