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"These data show Nplate increased platelet counts in most patients formost of the time, and clinically relevant bleeding was reduced over time,"said David J. Kuter, M.D., Chief of Hematology, Massachusetts GeneralHospital, Boston. "This is significant because Nplate can be a long-termtreatment for adult chronic ITP patients, who are at risk of serious bleedingevents if their platelet counts drop to less than 30,000 per microliter.These patients have had limited availability to long term treatment options."
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These study results showed that overall 74 percent of patients (160/215)achieved a platelet response defined as a platelet count of 50,000 plateletsper microliter and doubling of the baseline platelet count (median:17,000platelets per microliter). A platelet response was achieved by 30 percent(61/207) of patients after the first dose and by 47 percent (94/199) ofpatients after the third dose. The average treatment period was 76 weeks andthe longest duration of treatment was 204 weeks.
Additional key findings from the Extension study show:
-- Platelet counts increased: Platelet counts of Nplate-treated patientswere increased from baseline by 20,000 platelets per microliter more than 80percent of the time in 47 percent of patients and more than half the time in67 percent of patients.
-- Platelet counts maintained: Platelet count increases of 50,000platelets per microliter were sustained for greater than or equal to 10,greater than or equal to 25, and greater than or equal to 52 consecutive weeksin 77 percent (127/164), 67 percent (95/141), and 41 percent (48/116) ofpatients, respectively.
In this study, adverse events (AEs) did not increase with time and werereported in 86 percent of patients, with most mild to moderate in severity.The most common were headache (34 percent), contusion (32 percent), andfatigue (31 percent). Treatment-related and serious AEs were reported in 28percent and 29 percent of patients, respectively. Treatment-related seriousAEs were reported in 7 percent of patients. Five percent of patients (11/215)discontinued treatment due to AEs.
Bone marrow reticulin was present or increased in eight patients with noevidence of progression to collagen fibrosis or chronic idiopathicmyelofibrosis. Thrombotic/thromboembolic events were reported in sevenpatients, of whom six had pre-existing risk factors. To date, one patientdeveloped a neutralizing antibody to Nplate; however, it did not cross reactwith thrombopoietin and it was absent upon re-testing four months after Nplatetreatment was stopped.
This ongoing, open-label study is assessing the safety and efficacy oflong-term administration of Nplate in both splenectomized andnon-splenectomized adult chronic ITP patients. As of July 2008, 223 patientshad enrolled and 215 were treated with Nplate. Sixty-one percent of patientswere female and, of the enrolled patients, 44 percent had undergone asplenectomy (removal of the spleen).
Eligible patients had completed a previous ITP Nplate study, with nosignificant change in medical history. The Nplate starting dose was 1 ug/kg bysubcutaneous injection and was adjusted to maintain a platelet count between50,000 and 200,000 platelets per microliter.
Interim Phase 2 Nplate MDS Data Also Presented (Abstract # 224)
Interim data from an ongoing Phase 2 multicenter, randomized,double-blind, placebo-controlled study evaluating Nplate in patients with lowor intermediate risk MDS receiving azacytidine were also presented (n=40).The interim analysis showed that Nplate reduced the incidence of clinicallysignificant, treatment-related thrombocytopenic events and platelettransfusions. Nplate also improved the platelet nadir, defined as the lowestperipheral blood count that occurs secondary to bone marrow suppression, inMDS patients receiving azacytidine.
Each study arm was in combination with azacytidine, and serious AEs wereobserved in 77 percent of the placebo group, 46 percent of the Nplate 500uggroup and 71 percent of the 750ug group. One incident of each of the followingevents was reported: arthralgia, rash, hypersensitivity, pulmonary hemorrhage,hemorrhage and epistaxis. Two patients in the placebo group died, one offungal pneumonia and the other of pulmonary hemorrhage. One case of diseaseprogression from MDS to acute myeloid leukemia was observed in the Nplate500ug treated group.
About Adult ITP
In patients with ITP, platelets -- or blood cells needed to preventbleeding -- are destroyed by the patient's own immune system. Low plateletcounts leave adult ITP patients open to sudden serious bleeding events, makingit impossible to arrest blood flow. The risk for serious bleeding eventsincreases when platelet counts drop to less than 30,000 platelets permicroliter; normal counts range from 150,000 to 400,000 platelets permicroliter. ITP has historically been considered a disease of only plateletdestruction although recent data suggest that the body's natural plateletproduction processes in ITP are also unable to compensate for low levels ofplatelets in the blood. Increasing the rate of platelet production may addresslow platelet levels associated with ITP.
Currently available treatments (i.e., corticosteroids, immunglobulins)have limited application due to poor tolerability or transient effects.Surgical therapy (removal of the spleen) is also available to adult patientswith chronic ITP, but does not work in all cases. Currently, there are140,000 treated chronic ITP patients in Europe and the United States (U.S.).ITP affects about twice as many adult women as men.
About Myelodysplastic Syndromes
MDS is a disorder in which the production of blood cells by the bonemarrow is disrupted and loses its ability to produce normal cells. There is nocurative treatment for MDS, with the exception of bone marrow transplantation,and roughly 70 percent of all patients with MDS encounter complications orprogression due to acute myeloid leukemia. MDS affects all ages, from childrento adults, with the highest prevalence in those over sixty years of age.
Nplate is not indicated for the treatment of thrombocytopenia due to MDSor any cause of thrombocytopenia other than chronic ITP.
About Nplate
Nplate, Amgen's first peptibody, is a novel engineered therapeutic fusionprotein with attributes of both peptides and antibodies, but is distinct fromeach. Nplate works similarly to thrombopoietin (TPO), a natural protein in thebody. Nplate stimulates the TPO receptor, which is necessary for growth andmaturation of bone marrow cells that produce platelets.
Nplate was granted approval for the treatment of adult chronic ITP by theregulatory bodies in Australia in July and the U.S. in August 2008. InNovember 2008, the European Committee for Medicinal Products for Human Use(CHMP) issued a positive opinion recommending marketing authorization ofNplate in the European Union (EU). Amgen has also filed for regulatoryapproval of Nplate in Canada and Switzerland, and these applications arecurrently under review. Nplate has received orphan designation for ITP in theU.S. (2003), EU (2005), Switzerland (2005) and Japan (2006).
Nplate is indicated for the treatment of thrombocytopenia in patients withchronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had aninsufficient response to corticosteroids, immunoglobulins or splenectomy.Nplate should be used only in patients with ITP whose degree ofthrombocytopenia and clinical condition increases the risk for bleeding.Nplate should not be used in an attempt to normalize platelet counts.
Important Safety Information
Serious adverse reactions associated with Nplate in clinical studies werebone marrow reticulin deposition and worsening thrombocytopenia after Nplatediscontinuation.
Bone Marrow Reticulin Formation and Risk for Bone Marrow Fibrosis
-- Nplate administration increases the risk for development or progressionof reticulin fiber deposition within the bone marrow.
-- In clinical studies, Nplate was discontinued in four of the 271patients because of bone marrow reticulin deposition. Six additional patientshad reticulin observed upon bone marrow biopsy. All 10 patients with bonemarrow reticulin deposition had received Nplate doses greater than or equal to5 mcg/kg, and 6 received doses greater than or equal to 10 mcg/kg.
-- Progression to marrow fibrosis with cytopenias was not reported in thecontrolled clinical studies. In the extension study, one patient with ITP andhemolytic anemia developed marrow fibrosis with collagen during Nplatetherapy.
-- Clinical studies have not excluded a risk of bone marrow fibrosis withcytopenias.
-- Prior to initiation of Nplate examine the peripheral blood smearclosely to establish a baseline level of cellular morphologic abnormalities.Following identification of a stable Nplate dose, examine peripheral bloodsmears and CBCs monthly for new or worsening morphological abnormalities(e.g., teardrop and nucleated red blood cells, immature white blood cells) orcytopenia(s).
-- If the patient develops new or worsening morphological abnormalities orcytopenia(s), discontinue treatment with Nplate and consider a bone marrowbiopsy, including staining for fibrosis.
Worsened Thrombocytopenia After Cessation of Nplate
-- Discontinuation of Nplate may result in thrombocytopenia of greaterseverity than was present prior to Nplate therapy. This worsenedthrombocytopenia may increase the patient's risk of bleeding, particularly ifNplate is discontinued while the patient is on anticoagulants or antiplateletagents.
-- In clinical studies of patients with chronic ITP who had Nplatediscontinued, four of 57 patients developed thrombocytopenia of greaterseverity than was present prior to Nplate therapy.
-- This worsened thrombocytopenia resolved within 14 days.
-- Following discontinuation of Nplate, obtain weekly CBCs, includingplatelet counts, for at least two weeks and consider alternative treatmentsfor worsening thrombocytopenia, according to current treatment guidelines.
Thrombotic/Thromboembolic Complications
-- Thrombotic/thromboembolic complications may result from excessiveincreases in platelet counts. Excessive doses of Nplate or medication errorsthat result in excessive Nplate doses may increase platelet counts to a levelthat produces thrombotic/thromboembolic complications. In controlled clinicalstudies, the incidence of thrombotic/thromboembolic complications was similarbetween Nplate and placebo.
-- To minimize the risk for thrombotic/thromboembolic complications, donot use Nplate in an attempt to normalize platelet counts. Follow the doseadjustment guidelines to achieve and maintain a platelet count of greater thanor equal to 50 x 10(9)/L.
Lack or Loss of Response to Nplate
-- Hyporesponsiveness or failure to maintain a platelet response withNplate should prompt a search for causative factors, including neutralizingantibodies 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 andthrombopoietin (TPO).
-- Discontinue Nplate if the platelet count does not increase to a levelsufficient to avoid clinically important bleeding after 4 weeks at the highestweekly dose of 10 mcg/kg.
Hematological Malignancies and Progression of Malignancy in Patients witha Pre-existing Hematological Malignancy or Myelodysplastic Syndromes (MDS)
-- Nplate stimulation of the TPO receptor on the surface of hematopoieticcells may increase the risk for hematologic malignancies. In controlledclinical studies among patients with chronic ITP, the incidence of hematologicmalignancy was low and similar between Nplate and placebo.
-- In a separate single-arm clinical study of 44 patients withmyelodysplastic syndromes (MDS), 11 patients were reported as having possibledisease progression, among whom 4 patients had confirmation of acutemyelogenous leukemia (AML) during follow-up.
-- Nplate is not indicated for the treatment of thrombocytopenia due toMDS or any cause of thrombocytopenia other than chronic ITP.
Laboratory Monitoring
-- Monitor CBCs, including platelet counts and peripheral blood smears,prior to initiation, throughout, and following discontinuation of Nplatetherapy.
-- Prior to the initiation of Nplate, examine the peripheral blooddifferential to establish the baseline extent of red and white blood cellabnormalities.
-- Obtain CBCs, including platelet counts and peripheral blood smears,weekly during the dose adjustment phase of Nplate therapy and then monthlyfollowing establishment of a stable Nplate dose. Obtain CBCs, includingplatelet counts, weekly for at least 2 weeks following discontinuation ofNplate.
Nplate Distribution Program
-- Nplate is available only through a restricted distribution programcalled Nplate(TM) NEXUS (Network of Experts Understanding and SupportingNplate(TM) and Patients) Program. Under the Nplate(TM) NEXUS Program, onlyprescribers and patients registered with the program are able to prescribe,administer, and receive Nplate. This program provides educational materialsand a mechanism for the proper use of Nplate. To enroll in the Nplate(TM)NEXUS Program, call 1-877-NPLATE1 (1-877-675-2831).
General Safety
-- In the placebo-controlled studies, headache was the most commonlyreported adverse drug reaction, occurring in 35 percent of patients receivingNplate and 32 percent of patients receiving placebo. Headaches were usuallyof mild or moderate severity.
-- Most common adverse reactions (greater than or equal to 5 percenthigher patient incidence in Nplate versus placebo) were Arthralgia (26percent, 20 percent), Dizziness (17 percent, 0 percent), Insomnia (16 percent,7 percent), Myalgia (14 percent, 2 percent), Pain in Extremity (13 percent, 5percent) , Abdominal Pain (11 percent, 0 percent), Shoulder Pain (8 percent, 0percent), Dyspepsia (7 percent, 0 percent), and Paresthesia (6 percent, 0percent).
-- As with all therapeutic proteins, patients may develop antibodies tothe therapeutic protein.
About Amgen
Amgen discovers, develops, manufactures and delivers innovative humantherapeutics. A biotechnology pioneer since 1980, Amgen was one of the firstcompanies to realize the new science's promise by bringing safe and effectivemedicines from lab, to manufacturing plant, to patient. Amgen therapeuticshave changed the practice of medicine, helping millions of people around theworld in the fight against cancer, kidney disorder, rheumatoid arthritis, andother serious illnesses. With a deep and broad pipeline of potential newmedicines, Amgen remains committed to advancing science to dramaticallyimprove people's lives. To learn more about our pioneering science and ourvital medicines, visit http://www.amgen.com.
Forward-Looking Statement
This news release contains forward-looking statements that are based onmanagement's current expectations and beliefs and are subject to a number ofrisks, uncertainties and assumptions that could cause actual results to differmaterially from those described. All statements, other than statements ofhistorical fact, are statements that could be deemed forward-lookingstatements, including estimates of revenues, operating margins, capitalexpenditures, cash, other financial metrics, expected legal, arbitration,political, regulatory or clinical results or practices, customer andprescriber patterns or practices, reimbursement activities and outcomes andother such estimates and results. Forward-looking statements involvesignificant risks and uncertainties, including those discussed below and morefully described in the Securities and Exchange Commission (SEC) reports filedby Amgen, including Amgen's most recent annual report on Form 10-K and mostrecent periodic reports on Form 10-Q and Form 8-K. Please refer to Amgen'smost recent Forms 10-K, 10-Q and 8-K for additional information on theuncertainties and risk factors related to our business. Unless otherwisenoted, Amgen is providing this information as of Dec. 8, 2008 and expresslydisclaims any duty to update information contained in this news release.
No forward-looking statement can be guaranteed and actual results maydiffer materially from those we project. Discovery or identification of newproduct candidates or development of new indications for existing productscannot be guaranteed and movement from concept to product is uncertain;consequently, there can be no guarantee that any particular product candidateor development of a new indication for an existing product will be successfuland become a commercial product. Further, preclinical results do notguarantee safe and effective performance of product candidates in humans. Thecomplexity of the human body cannot be perfectly, or sometimes, evenadequately modeled by computer or cell culture systems or animal models. Thelength of time that it takes for us to complete clinical trials and obtainregulatory approval for product marketing has in the past varied and we expectsimilar variability in the future. We develop product candidates internallyand through licensing collaborations, partnerships and joint ventures.Product candidates that are derived from relationships may be subject todisputes between the parties or may prove to be not as effective or as safe aswe may have believed at the time of entering into such relationship. Also, weor others could identify safety, side effects or manufacturing problems withour products after they are on the market. Our business may be impacted bygovernment investigations, litigation and products liability claims. Wedepend on third parties for a significant portion of our manufacturingcapacity for the supply of certain of our current and future products andlimits on supply may constrain sales of certain of our current products andproduct candidate development.
In addition, sales of our products are affected by the reimbursementpolicies imposed by third-party payors, including governments, privateinsurance plans and managed care providers and may be affected by regulatory,clinical and guideline developments and domestic and international trendstoward managed care and healthcare cost containment as well as U.S.legislation affecting pharmaceutical pricing and reimbursement. Governmentand others' regulations and reimbursement policies may affect the development,usage and pricing of our products. In addition, we compete with othercompanies with respect to some of our marketed products as well as for thediscovery and development of new products. We believe that some of our newerproducts, product candidates or new indications for existing products, mayface competition when and as they are approved and marketed. Our products maycompete against products that have lower prices, established reimbursement,superior performance, are easier to administer, or that are otherwisecompetitive with our products. In addition, while we routinely obtain patentsfor our products and technology, the protection offered by our patents andpatent applications may be challenged, invalidated or circumvented by ourcompetitors and there can be no guarantee of our ability to obtain or maintainpatent protection for our products or product candidates. We cannot guaranteethat we will be able to produce commercially successful products or maintainthe commercial success of our existing products. Our stock price may beaffected by actual or perceived market opportunity, competitive position, andsuccess or failure of our products or product candidates. Further, thediscovery of significant problems with a product similar to one of ourproducts that implicate an entire class of products could have a materialadverse effect on sales of the affected products and on our business andresults of operations.
The scientific information discussed in this news release related to ourproduct candidates is preliminary and investigative. Such product candidatesare not approved by the U.S. Food and Drug Administration (FDA), and noconclusions can or should be drawn regarding the safety or effectiveness ofthe product candidates. Only the FDA can determine whether the productcandidates are safe and effective for the use(s) being investigated. Further,the scientific information discussed in this news release relating to newindications for our products is preliminary and investigative and is not partof the labeling approved by the FDA for the products. The products are notapproved for the investigational use(s) discussed in this news release, and noconclusions can or should be drawn regarding the safety or effectiveness ofthe products for these uses. Only the FDA can determine whether the productsare safe and effective for these uses. Healthcare professionals should referto and rely upon the FDA-approved labeling for the products, and not theinformation discussed in this news release.CONTACT: Amgen, Thousand Oaks Trish Hawkins, 805-447-5631 (US media) Sabeena Ahmad, +41 41 3692 530 (EU media, oncology) Arvind Sood: 805 447-1060 (investors) (Logo: http://www.newscom.com/cgi-bin/prnh/20081015/AMGENLOGO)
SOURCE Amgen Inc.
