FDA Apprves Nplate
FDA Approves Nplate for Long-Term Treatment of Adult Chronic ITP
THOUSAND OAKS, Calif.--(BUSINESS WIRE)--Aug 22, 2008 - Amgen Inc. (NASDAQ: AMGN) today announced that the United States (U.S.) Food and Drug Administration (FDA) has approved Nplate (romiplostim), the first and only platelet producer for the treatment of thrombocytopenia in splenectomized (spleen removed) and non-splenectomized adults with chronic immune thrombocytopenic purpura (ITP). Nplate, the first FDA-approved peptibody protein, works by raising and sustaining platelet counts, representing a novel approach for the long-term treatment of this chronic disease.
Chronic ITP is a serious autoimmune disorder characterized by low platelet counts in the blood (thrombocytopenia), which can lead to serious bleeding events. Recognized as an orphan disease, chronic ITP affects an estimated 60,000 adult patients in the U.S. and is considered an unmet need by the FDA.
"Until now, patients suffering from chronic ITP have had limited available treatment options, many of which are often unsuitable for long-term use due to side effects and tolerability issues," said David J. Kuter, M.D., Chief of Hematology, Massachusetts General Hospital, Boston. "Nplate represents the first long-term treatment for adult chronic ITP patients, providing a new treatment approach for this chronic disease."
The FDA approval of Nplate was based on efficacy and safety results from two pivotal Phase 3 studies of adult patients with chronic ITP, including both splenectomized and non-splenectomized patients. The overall response rate for Nplate was 83 percent (n=69/83, p less than 0.0001) of treated splenectomized and non-splenectomized patients, and platelet counts were raised and sustained in these six month studies. Additionally, patients treated with Nplate were able to reduce or discontinue their use of concomitant ITP medications and emergency medications (i.e., corticosteroids, IVIG, Win-Rho, Anti-D therapy).
Specifically, in the Phase 3 studies, non-splenectomized patients had an 88 percent (n=36/41, p less than 0.0001) overall platelet response and splenectomized patients had a 79 percent (n=33/42, p less than 0.0001) overall platelet response rate. Combined data from both trials shows clinically relevant bleeding events were significantly reduced by half in patients treated with Nplate compared to placebo (15 percent vs. 34 percent, p=0.018). Amgen continues to study the long-term efficacy and safety of Nplate for which there is more than three years of follow up safety and efficacy data.
"For those suffering from ITP, the daily fear of experiencing a serious bleeding episode can be emotionally stressful and extremely difficult for both patients and their families. We welcome the addition of new treatment options which offer new hope for the treatment of this serious disease," said Craig Conway, executive director of the Platelet Disorder Support Association.
In addition to improved clinical benefits, described in the FDA labeling, Amgen believes Nplate offers patients a positive net health benefit with fewer hospitalizations from bleeding events, as well as reduced need for emergency medications (IVIG and Win-Rho). Amgen expects the total costs of care for chronic ITP patients managed with Nplate to be less than or comparable to the total costs of care with standard treatment regimens.
Amgen also announced it will launch the Nplate NEXUS (Network of EXperts Understanding and Supporting Nplate and Patients) Program, a multi-faceted program designed to provide comprehensive access, support and education for chronic ITP patients, their caregivers and healthcare providers. The Nplate NEXUS Program is part of the Risk Evaluation and Mitigation Strategy (REMS) developed by Amgen in partnership with the FDA to assure safe use of Nplate while minimizing risk. The program will facilitate appropriate use of Nplate, provide patient support through education and resources and help with ongoing follow up through safety data collection.
Through the Nplate NEXUS Program, eligible patients who are uninsured, underinsured, or unable to afford their insurance co-payments may be able to receive reimbursement support and other assistance from Amgen. For example, one such program helps cover up to 50 percent of an eligible, commercially-insured patient's co-payments for Nplate. Recognizing that some patients may not have healthcare coverage, Amgen continues to offer another program for all of its innovative products, including Nplate, which provides product free of charge to eligible, low-income patients without insurance.
"Amgen is committed to advancing the discovery and development of new therapies for grievous illnesses where there is unmet medical need," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "The FDA approval of Nplate is the result of more than 15 years of research and represents an important biotechnology milestone as it is the first FDA-approved peptibody protein, an innovative platform for delivering targeted therapies."
Nplate was also approved for ITP by Australia's Therapeutic Goods Administration (TGA) in July 2008. Amgen has filed for regulatory approval of Nplate in the European Union (EU), Canada, and Switzerland and these applications are currently under review. Nplate has also received orphan designation for ITP in the EU (2005), Switzerland (2005) and Japan (2006).
More information about the Nplate NEXUS Program is available by calling 1-877-NPLATE1 (1-877-675-2831), or by visiting www.nplate.com.
About Adult ITP
Platelets are blood cells needed to prevent bleeding. Low platelet counts leave adult ITP patients open to sudden serious bleeding events, making it impossible to arrest blood flow. The risk for serious bleeding events increases when platelet counts drop to less than 30,000 platelets per microliter.
There are limited approved treatments (i.e., corticosteroids, immunoglobulins) or surgical therapy (removal of the spleen) available to adult patients with chronic ITP. Currently, there are 140,000 treated chronic ITP patients in the U.S. and Europe. ITP affects about twice as many adult women as men.
With ITP, platelets are destroyed by the patient's own immune system. ITP has historically been considered a disease of platelet destruction. However, recent data also suggest that the body's natural platelet production processes are unable to compensate for low levels of platelets in the blood. Increasing the rate of platelet production may address low platelet levels associated with ITP.
Nplate, Amgen's first peptibody protein, is a novel engineered therapeutic fusion protein with attributes of both peptides and antibodies, but is distinct from each. Nplate works similarly to thrombopoietin (TPO), a natural protein in the body. Nplate stimulates the TPO receptor, which is necessary for growth and maturation of bone marrow cells that produce platelets.
Important Safety Information
Serious adverse reactions associated with Nplate in clinical studies were bone marrow reticulin deposition and worsening thrombocytopenia after Nplate discontinuation.
Bone Marrow Reticulin Formation and Risk for Bone Marrow Fibrosis
-- Nplate administration increases the risk for development or progression of reticulin fiber deposition within the bone marrow.
-- In clinical studies, Nplate was discontinued in four of the 271 patients because of bone marrow reticulin deposition. Six additional patients had reticulin observed upon bone marrow biopsy. All 10 patients with bone marrow reticulin deposition had received Nplate doses greater than or equal to 5 mcg/kg, and 6 received doses greater than or equal to 10 mcg/kg.
-- Progression to marrow fibrosis with cytopenias was not reported in the controlled clinical studies. In the extension study, one patient with ITP and hemolytic anemia developed marrow fibrosis with collagen during Nplate therapy.
-- Clinical studies have not excluded a risk of bone marrow fibrosis with cytopenias.
-- Prior to initiation of Nplate examine the peripheral blood smear closely to establish a baseline level of cellular morphologic abnormalities. Following identification of a stable Nplate dose, examine peripheral blood smears and CBCs monthly for new or worsening morphological abnormalities (eg, teardrop and nucleated red blood cells, immature white blood cells) or cytopenia(s).
-- If the patient develops new or worsening morphological abnormalities or cytopenia(s), discontinue treatment with Nplate and consider a bone marrow biopsy, including staining for fibrosis.
Worsened Thrombocytopenia After Cessation of Nplate
-- Discontinuation of Nplate may result in thrombocytopenia of greater severity than was present prior to Nplate therapy. This worsened thrombocytopenia may increase the patient's risk of bleeding, particularly if Nplate is discontinued while the patient is on anticoagulants or antiplatelet agents.
-- In clinical studies of patients with chronic ITP who had Nplate discontinued, four of 57 patients developed thrombocytopenia of greater severity than was present prior to Nplate therapy.
-- This worsened thrombocytopenia resolved within 14 days.
-- Following discontinuation of Nplate, obtain weekly CBCs, including platelet counts, for at least two weeks and consider alternative treatments for worsening thrombocytopenia, according to current treatment guidelines.
-- Thrombotic/thromboembolic complications may result from excessive increases in platelet counts. Excessive doses of Nplate or medication errors that result in excessive Nplate doses may increase platelet counts to a level that produces thrombotic/thromboembolic complications. In controlled clinical studies, the incidence of thrombotic/thromboembolic complications was similar between Nplate and placebo.
-- To minimize the risk for thrombotic/thromboembolic complications, do not use Nplate in an attempt to "normalize" platelet counts. Follow the dose adjustment guidelines to achieve and maintain a platelet count of greater than or equal to 50 x 10 to the ninth/L.
Lack or Loss of Response to Nplate
-- Hyporesponsiveness or failure to maintain a platelet response with Nplate should prompt a search for causative factors, including neutralizing antibodies to Nplate or bone marrow fibrosis.
-- To detect antibody formation, submit blood samples to Amgen (1-800-772-6436). Amgen will assay these samples for antibodies to Nplate and thrombopoietin (TPO).
-- Discontinue Nplate if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks at the highest weekly dose of 10 mcg/kg.
Hematological Malignancies and Progression of Malignancy in Patients with a Pre-existing Hematological Malignancy or Myelodysplastic Syndrome (MDS)
-- Nplate stimulation of the TPO receptor on the surface of hematopoietic cells may increase the risk for hematologic malignancies. In controlled clinical studies among patients with chronic ITP, the incidence of hematologic malignancy was low and similar between Nplate and placebo.
-- In a separate single-arm clinical study of 44 patients with myelodysplastic syndromes (MDS), 11 patients were reported as having possible disease progression, among whom 4 patients had confirmation of acute myelogenous leukemia (AML) during follow-up.
-- Nplate is not indicated for the treatment of thrombocytopenia due to MDS or any cause of thrombocytopenia other than chronic ITP.
-- Monitor CBCs, including platelet counts and peripheral blood smears, prior to initiation, throughout, and following discontinuation of Nplate therapy.
-- Prior to the initiation of Nplate, examine the peripheral blood differential to establish the baseline extent of red and white blood cell abnormalities.
-- Obtain CBCs, including platelet counts and peripheral blood smears, weekly during the dose adjustment phase of Nplate therapy and then monthly following establishment of a stable Nplate dose. Obtain CBCs, including platelet counts, weekly for at least 2 weeks following discontinuation of Nplate.
Nplate Distribution Program
-- Nplate is available only through a restricted distribution program called Nplate NEXUS (Network of Experts Understanding and Supporting Nplate and Patients) Program. Under the Nplate NEXUS Program, only prescribers and patients registered with the program are able to prescribe, administer, and receive Nplate. This program provides educational materials and a mechanism for the proper use of Nplate. To enroll in the Nplate NEXUS Program, call 1-877-NPLATE1 (1-877-675-2831).
-- In the placebo-controlled studies, headache was the most commonly reported adverse drug reaction, occurring in 35 percent of patients receiving Nplate and 32 percent of patients receiving placebo. Headaches were usually of mild or moderate severity.
-- Most common adverse reactions (greater than or equal to 5 percent higher patient incidence in Nplate versus placebo) were Arthralgia (26 percent, 20 percent), Dizziness (17 percent, 0 percent), Insomnia (16 percent, 7 percent), Myalgia (14 percent, 2 percent), Pain in Extremity (13 percent, 5 percent) , Abdominal Pain (11 percent, 0 percent), Shoulder Pain (8 percent, 0 percent), Dyspepsia (7 percent, 0 percent), and Paresthesia (6 percent, 0 percent).
-- As with all therapeutic proteins, patients may develop antibodies to the therapeutic protein.
Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com.
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Posted: August 2008
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