FDA Approves New Kyprolis Combination Therapy

Amgen announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) of Kyprolis^® (carfilzomib) for Injection in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy. The FDA also approved Kyprolis as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy. This FDA decision converts to full approval the initial accelerated approval Kyprolis received in July 2012 as a single agent.

This new indication for Kyprolis is the second in six months. In July 2015, the FDA approved another expanded indication for Kyprolis in combination with lenalidomide and dexamethasone (KRd) for the treatment of patients with multiple myeloma who have received one to three prior lines of therapy.

Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse.  It is a rare and very aggressive disease that accounts for approximately one percent of all cancers. In the U.S., there are nearly 90,000 people living with, or in remission from, multiple myeloma. Approximately, 26,850 Americans are diagnosed with multiple myeloma each year and 11,240 patient deaths are reported on an annual basis.

European Commission Approves IMLYGIC As First Oncolytic Immunotherapy

Amgen announced that the European Commission has approved the use of IMLYGIC™ (talimogene laherparepvec) for the treatment of adults with unresectable melanoma that is regionally or distantly metastatic (Stage IIIB, IIIC and IVM1a), with no bone, brain, lung or other visceral disease. IMLYGIC is the first oncolytic immunotherapy to demonstrate therapeutic benefit for patients with metastatic melanoma in a Phase 3 clinical trial. 

IMLYGIC is derived from the herpes simplex type 1 virus (HSV-1) , commonly called the cold sore virus. IMLYGIC has been modified to replicate within tumors and to produce the immune stimulatory protein human granulocyte-macrophage colony-stimulating factor (GM-CSF). Administered via intralesional injection, IMLYGIC is designed to cause the death of tumor cells and initiate an anti-tumor immune response.  

Melanoma remains a significant public health concern in the European Union (EU), with an estimated 22,000 deaths from the disease in 2012. While melanoma is curable when detected in the early stages, metastatic melanoma continues to be one of the most difficult-to-treat cancers because it is highly aggressive and complex. Even with recent new options in immune-oncology, a large number of patients with metastatic melanoma still do not respond to treatment.

The most commonly reported treatment-related adverse events were fatigue, chills, pyrexia, nausea, influenza-like illness and injection-site pain. Overall, 98 percent of these adverse reactions reported were mild or moderate in severity. The most common grade 3 or higher adverse reaction was cellulitis. No fatal treatment-related adverse events occurred.

Amgen to Present IMLYGIC Data

Amgen announced that the Company will present eight IMLYGIC (talimogene laherparepvec) abstracts, including data from the Phase 3 trial and new data from its Phase 1b combination trial with Merck's anti-PD-1 therapy, at the 12^th International Congress of the Society for Melanoma Research (SMR), to be held on Nov. 18-21 in San Francisco. 

The Phase 1b data on IMLYGIC in combination with an investigational use of Merck's anti-PD-1 therapy, KEYTRUDA^® (pembrolizumab), in patients with unresectable metastatic melanoma has been accepted as a late-breaking abstract.

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 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.

Amgen present data on REPATHA

Amgen announced that it will present 14 abstracts at the American Heart Association (AHA) Scientific Sessions 2015, from Nov. 7–11 in Orlando, Fla. New data analyses evaluating Repatha™ (evolocumab), an injectable proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor approved for certain patients with high low-density lipoprotein cholesterol (LDL-C), or "bad" cholesterol, and Corlanor^® (ivabradine), an oral medicine for certain people who have chronic (long-lasting) heart failure caused by the lower-left part of their heart not contracting well, will be presented at the meeting. 

Repatha, approved by the U.S. Food and Drug Administration (FDA) on Aug. 27, is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD), who require additional lowering of LDL-C; and as an adjunct to diet and other LDL-lowering therapies for the treatment of patients with homozygous familial hypercholesterolemia (HoFH), who require additional lowering of LDL-C. The effect of Repatha on cardiovascular morbidity and mortality has not been determined.  

Corlanor, approved by the FDA on April 15, is indicated to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction <35 percent, who are in sinus rhythm with resting heart rate >70 beats per minute and either are on maximally tolerated doses of beta blockers or have a contraindication to beta blocker use.

In addition to Repatha and Corlanor clinical trial analyses, data from Amgen's Center for Observational Research will be presented, including a poster and oral presentation on findings from the REGARDS (REasons for Geographic And Racial Differences in Stroke) study, and an oral presentation on the benefits of initiating beta blocker treatment in heart failure patients within seven days following hospital discharge. A global health economics study on the association between achievement of LDL-C reduction targets and cardiovascular disease risk among patients with familial hypercholesterolemia will also be presented.

Amgen Receives CHMP Positive Opinions For Kyprolis

Amgen announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted positive opinions recommending marketing authorization for: Kyprolis (carfilzomib) in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. BLINCYTO^® (blinatumomab) as a conditional marketing authorization for the treatment of adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL).

Kyprolis is a proteasome inhibitor for use in the treatment of patients with relapsed multiple myeloma. Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed. Kyprolis blocks proteasomes, which leads to an excessive build-up of proteins within cells. 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.

BLINCYTO is the first clinical validation of the bispecific T cell engager (BiTE^®) platform, an innovative approach that can help the body's own immune system fight cancer. 

The CHMP positive opinions will now be reviewed by the European Commission and if granted, the two products will have marketing authorization in the 28 member countries of the European Union (EU), as well as Iceland, Lichtenstein and Norway.

Amgen Submits Application To FDA For New Delivery Option For Monthly Administration Of Repatha

Amgen announced the submission of an application to the U.S. Food and Drug Administration (FDA) seeking approval of a single-dosing option for the monthly administration of Repatha (evolocumab) Injection, allowing the 420 mg monthly dose to be administered as a single injection. Approved by the FDA on Aug. 27, 2015, Repatha is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protein that reduces the liver's ability to remove low-density lipoprotein cholesterol (LDL-C), or "bad" cholesterol, from the blood.

Repatha is approved as an adjunct to diet and maximally tolerated statins in patients with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD), who require additional lowering of LDL-C; and as an adjunct to diet and other LDL-lowering therapies for the treatment of patients with homozygous familial hypercholesterolemia (HoFH), who require additional lowering of LDL-C. The effect of Repatha on cardiovascular morbidity and mortality has not been determined.

Repatha (evolocumab) is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9).1 Repatha binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, Repatha increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.

Amgen Submits Marketing Authorization Application Etelcalcetide (AMG 416)

Amgen announced the submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) via the centralized procedure for etelcalcetide (formerly AMG 416) for the treatment of secondary hyperparathyroidism (SHPT) in adult patients with chronic kidney disease (CKD) on hemodialysis therapy. If approved, etelcalcetide will be the first calcimimetic agent that can be administered intravenously.

 

Etelcalcetide is a novel calcimimetic agent that suppresses the secretion of parathyroid hormone and is in clinical development for the treatment of SHPT in patients with CKD on hemodialysis. Etelcalcetide is administered intravenously three times per week at the end of each dialysis session. It acts by binding to and activating the calcium-sensing receptor on the parathyroid gland, thereby causing decreases in parathyroid hormone (PTH). Sustained elevations in PTH are known to be associated with significant clinical consequences for patients with CKD.

The MAA submission for etelcalcetide includes data from three Phase 3 studies, all of which met their primary endpoints, including two pooled placebo-controlled trials in more than 1,000 patients and a head-to-head study evaluating etelcalcetide compared with cinacalcet.

SHPT is a common and serious condition that is often progressive among patients with CKD, and it affects many of the approximately two million people throughout the world who are receiving dialysis, including approximately 350,000 people in Europe. The disorder develops early in the course of CKD and usually manifests as increased levels of PTH as a result of increased production from the parathyroid glands (four small glands in the neck). Patients with end stage renal disease who require maintenance dialysis often have substantial elevations of PTH that are commonly associated with abnormal calcium and phosphorus and an increased risk of significant clinical consequences.