On December 5, 2015 CTI BioPharma Corp. (CTI BioPharma) (NASDAQ and MTA: CTIC) and Baxalta Incorporated (Baxalta) (NYSE: BXLT) reported results from a new analysis of the pivotal Phase 3 trial, PERSIST-1, evaluating pacritinib versus best available therapy, excluding treatment with JAK2 inhibitors (BAT), in patients with myelofibrosis (Press release, CTI BioPharma, DEC 5, 2015, View Source;p=RssLanding&cat=news&id=2120391 [SID:1234508415]). Data examining patient outcomes across baseline demographic factors that are associated with prognosis – including age, baseline hemoglobin, baseline platelet count, ECOG status, JAK2 mutation status and red blood cell transfusion dependency – showed that treatment with pacritinib resulted in consistent rates of spleen volume reduction and control of disease-related symptoms across all intermediate or high-risk myelofibrosis subgroups. These findings were presented by Alessandro M. Vannucchi, M.D., associate professor of Hematology, University of Florence, Italy, during an oral presentation at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) (ASH 2015) Annual Meeting & Exposition in Orlando (Abstract #58).

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Pacritinib is an investigational oral multikinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R, which are kinases found to be involved in the growth and spread of myelofibrosis and other blood-related cancers such as acute myeloid leukemia (AML).

"Reducing the burden of myelofibrosis-related symptoms is an important goal of treatment. However, for patients diagnosed with this rare blood cancer, there are limited therapeutic options – a gap that is even more significant for patients with low platelet counts," said Prof. Vannucchi. "These data presented at ASH (Free ASH Whitepaper) 2015 are important and clinically meaningful as they demonstrate pacritinib’s potential to achieve treatment goals across intermediate or high-risk patients with myelofibrosis, regardless of baseline characteristics including starting platelet count."

Myelofibrosis is a rare blood cancer associated with significantly reduced quality of life and shortened survival. Most patients with the disease present with enlarged spleens (splenomegaly), as well as many other potentially devastating physical symptoms such as abdominal discomfort, bone pain, feeling full after eating little, severe itching, night sweats and extreme fatigue.

"The results from this analysis add to the growing body of data for pacritinib suggesting it is a unique JAK inhibitor with a differentiated efficacy and safety profile that is not limited by the baseline characteristics of patients with myelofibrosis," said James Bianco, M.D., President and Chief Executive Officer, CTI BioPharma. "We believe pacritinib has the potential to fill a gap that exists for many patients whose lives are profoundly impacted by myelofibrosis, particularly those patients with low platelet counts."

"We are developing pacritinib with particular focus on targeting the underlying biology of myelofibrosis to improve the treatment landscape for patients with this underserved, progressive disease, including those in intermediate and high-risk subgroups," said David Meek, Executive Vice President and President, Oncology at Baxalta. "We look forward to working with worldwide regulatory authorities to advance treatment options for all patients with myelofibrosis as we begin our registration submissions for pacritinib in the coming months."

About the Subgroup Analysis
Findings presented at ASH (Free ASH Whitepaper) 2015 were based on the analysis of baseline patients’ characteristics from PERSIST-1, a randomized Phase 3 registration-directed trial comparing the efficacy and safety of pacritinib to BAT that included a broad range of currently utilized treatments. As previously reported, the trial met its primary endpoint of spleen volume reduction (35 percent or greater from baseline to Week 24 by MRI/CT scan) in the intent-to-treat population.

The subgroup analysis discussed above assessed results observed in patients achieving 35 percent or greater spleen volume reduction from baseline or a decrease of 50 percent or more in Total Symptom Score (TSS) by baseline characteristics or risk factors, including initial platelet count, JAK2V617F mutation status, red blood cell transfusions and bone pain. Findings showed that results (from the primary analysis) were consistent across all subgroups evaluated. Achievement of 35 percent or greater spleen volume reduction was independent of most risk factors assessed and a 50 percent or more decrease in TSS was independent of characteristics evaluated, except bone pain score greater than three at baseline.

The most common adverse events in the pacritinib arm vs. BAT that showed more than 5 percent difference were diarrhea (57 percent vs. 12 percent), nausea (29 percent vs. 6 percent) and vomiting (19 percent vs. 5 percent). No Grade 4 gastrointestinal events were reported.

Additional Pacritinib Data Presented at ASH (Free ASH Whitepaper)
Also presented today were patient-reported outcome data that examined the relationship between myelofibrosis-associated symptoms (based on the TSS) and changes in splenomegaly and health-related quality of life (HRQoL) outcomes in the PERSIST-1 overall patient population and in patients with baseline thrombocytopenia. The analysis showed TSS response was associated with improvements in spleen volume response and perceived Overall Health State; this trend was also observed in patients with low baseline platelet counts (<50,000/µL and <100,000/ µL). In all patient populations analyzed, TSS response was significantly associated with improvements in fatigue, a major contributor to poor HRQoL in patients with myelofibrosis. Significant improvements in social functioning, appetite loss and insomnia were also observed in patients with baseline thrombocytopenia. These data were presented in a poster presentation by Ruben Mesa, M.D., Chair, Hematology and Medical Oncology Division, Mayo Clinic, Scottsdale, AZ (Abstract #1609).

About PERSIST-1
PERSIST-1 is a randomized (2:1), controlled Phase 3 registration-directed trial comparing the efficacy and safety of pacritinib to BAT – which included a broad range of currently utilized treatments – in 327 patients with myelofibrosis (primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis), regardless of the patients’ platelet counts. At study entry, 46 percent of patients were thrombocytopenic; 32 percent of patients had platelet counts less than 100,000 per microliter (<100,000/µL); and 16 percent of patients had platelet counts less than 50,000 per microliter (<50,000/µL); normal platelet counts range from 150,000 to 450,000 per microliter. The median duration of treatment was 16.2 months in patients treated with pacritinib, compared to 5.9 months in patients treated with BAT. The majority (79 percent) of patients on the BAT arm eventually crossed over to receive pacritinib therapy.

About Pacritinib
Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. In August 2014, pacritinib was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of intermediate and high-risk myelofibrosis, including but not limited to patients with disease-related thrombocytopenia, patients experiencing treatment-emergent thrombocytopenia on other JAK2 inhibitor therapy or patients who are intolerant of, or whose symptoms are sub-optimally managed on other JAK2 inhibitor therapy.

CTI BioPharma and Baxalta are parties to a worldwide license agreement to develop and commercialize pacritinib. CTI BioPharma and Baxalta will jointly commercialize pacritinib in the U.S. while Baxalta has exclusive commercialization rights for all indications outside the U.S.

The companies recently announced the initiation of a rolling new drug application (NDA) to the FDA for pacritinib. The companies are seeking accelerated approval and priority review of pacritinib for the treatment of patients with intermediate and high-risk myelofibrosis with low platelet counts of less than 50,000 per microliter (<50,000/μL).

About Myelofibrosis and Myeloproliferative Neoplasms
Myelofibrosis is one of three main types of myeloproliferative neoplasms (MPN), which are a closely related group of hematological blood cancers. The three main types of MPNs are myelofibrosis, polycethemia vera and essential thrombocythemia.1 Myelofibrosis is a serious and life-threatening chronic bone marrow disorder caused by the accumulation of malignant bone marrow cells that triggers an inflammatory response and scars the bone marrow. The replacement of bone marrow with scar tissue limits its ability to produce red blood cells, prompting the spleen and liver to take over this function. Symptoms that arise from this disease include enlargement of the spleen, anemia, extreme fatigue and pain. As the disease progresses, the body slows production of important blood cells, and within one year of diagnosis, the incidence of disease-related thrombocytopenia (very low blood platelet counts), anemia and red blood cell transfusion requirements increase significantly.

The estimated prevalence of MPNs suggest there are approximately 300,000 people living with the disease in the U.S., of which myelofibrosis accounts for approximately 18,000 patients.2 In Europe, there is a wide variation of prevalence observed across data sources. Myelofibrosis has a median age of 64 at the time of diagnosis2 and is a progressive disease with approximately 20 percent of patients eventually developing AML.3 The median survival for high-risk myelofibrosis patients is less than one and a half years, while the median survival for myelofibrosis patients overall is approximately six years.4

On December 5, 2015 Celgene Corporation (NASDAQ:CELG) reported that the addition of bortezomib to REVLIMID (lenalidomide) and low-dose dexamethasone (RVd), the standard of myeloma therapy, significantly improved progression-free survival (PFS) compared to lenalidomide and low-dose dexamethasone (Rd) in patients newly-diagnosed with multiple myeloma (Press release, Celgene, DEC 5, 2015, View Source [SID:1234508414]). The phase 3 study was conducted by SWOG, a publicly funded international cancer clinical trials network and presented at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

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In the 471-patient study, patients receiving RVd achieved a median PFS of 43 months compared to a median PFS of 30 months for patients who received Rd alone (HR = 0.712, 96% CI, one-sided p=0.0018 (two-sided p=0.0037)). The data also show that overall survival (OS) was improved for RVd compared to Rd. Patients who received RVd had a median OS of 75 months compared to a median 64 months for patients receiving Rd (HR=0.709, 96% CI, one-sided p=0.0125 (two-sided p=0.250)).

Grade 3 or higher adverse events by common toxicity criteria category seen in patients receiving RVd vs. Rd, respectively, were neurologic (33% vs. 11%), pain (12% vs. 4%), sensory (23% vs. 3%), and gastrointestinal (22% vs. 8%). Second primary malignancies occurred in 20 patients, including 10 (4%) on RVd and 10 (4%) on Rd.

"This study is a great example of how new combinations are building on the backbone of myeloma research with REVLIMID and low-dose dexamethasone," said Markus Renschler, M.D., Senior Vice President, Global Head of Hematology & Oncology Medical Affairs for Celgene. "The study demonstrated that adding bortezomib to standard care REVLIMID and dexamethasone improved remission rates and extended the duration of disease control."

The combination of REVLIMID, low-dose dexamethasone and bortezomib is not approved for any indication in any country.

About REVLIMID

In the United States, REVLIMID is approved in combination with dexamethasone for the treatment of patients with multiple myeloma. REVLIMID is also approved in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy in nearly 70 countries, encompassing Europe, the Americas, the Middle East and Asia, and in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy in Australia and New Zealand.

REVLIMID is also approved in the United States, Canada, Switzerland, Australia, New Zealand and several Latin American countries, as well as Malaysia and Israel, for transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities and in Europe for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate.

In addition, REVLIMID is approved in the United States for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib.

U.S. Regulatory Information for REVLIMID

REVLIMID (lenalidomide) in combination with dexamethasone (dex) is indicated for the treatment of patients with multiple myeloma (MM)

REVLIMID is indicated for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities

REVLIMID is indicated for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib

REVLIMID is not indicated and not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials

REVLIMID is a registered trademark of Celgene Corporation.

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity

Do not use REVLIMID during pregnancy. Lenalidomide, a thalidomide analogue, caused limb abnormalities in a developmental monkey study. Thalidomide is a known human teratogen that causes severe life-threatening human birth defects. If lenalidomide is used during pregnancy, it may cause birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting REVLIMID treatment. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after REVLIMID treatment. To avoid embryo-fetal exposure to lenalidomide, REVLIMID is only available through a restricted distribution program, the REVLIMID REMS program (formerly known as the "RevAssist"program).

Information about the REVLIMID REMS program is available at www.celgeneriskmanagement.com or by calling the manufacturer’s toll-free number 1-888-423-5436.

Hematologic Toxicity (Neutropenia and Thrombocytopenia)

REVLIMID can cause significant neutropenia and thrombocytopenia. Eighty percent of patients with del 5q MDS had to have a dose delay/reduction during the major study. Thirty-four percent of patients had to have a second dose delay/reduction. Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled in the study. Patients on therapy for del 5q MDS should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter. Patients may require dose interruption and/or reduction. Patients may require use of blood product support and/or growth factors.

Venous and Arterial Thromboembolism

REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as risk of myocardial infarction and stroke in patients with MM who were treated with REVLIMID and dexamethasone therapy. Monitor for and advise patients about signs and symptoms of thromboembolism. Advise patients to seek immediate medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. Thromboprophylaxis is recommended and the choice of regimen should be based on an assessment of the patient’s underlying risks.

CONTRAINDICATIONS

Pregnancy: REVLIMID can cause fetal harm when administered to a pregnant female and is contraindicated in females who are pregnant. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus

Allergic Reactions: REVLIMID is contraindicated in patients who have demonstrated hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis) to lenalidomide

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity:

REVLIMID is an analogue of thalidomide, a known human teratogen that causes life-threatening human birth defects or embryo-fetal death. An embryo-fetal development study in monkeys indicates that lenalidomide produced malformations in offspring of female monkeys who received drug during pregnancy, similar to birth defects observed in humans following exposure to thalidomide during pregnancy

Females of Reproductive Potential: Must avoid pregnancy for at least 4 weeks before beginning REVLIMID therapy, during therapy, during dose interruptions and for at least 4 weeks after completing therapy. Must commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control beginning 4 weeks prior to initiating treatment with REVLIMID, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of REVLIMID. Must obtain 2 negative pregnancy tests prior to initiating therapy

Males: Lenalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking REVLIMID and for up to 28 days after discontinuing REVLIMID, even if they have undergone a successful vasectomy. Male patients taking REVLIMID must not donate sperm
Blood Donation: Patients must not donate blood during treatment with REVLIMID and for 1 month following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to REVLIMID
REVLIMID REMS Program

Because of embryo-fetal risk, REVLIMID is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) the REVLIMID REMS Program (formerly known as the "RevAssist" Program). Prescribers and pharmacies must be certified with the program and patients must sign an agreement form and comply with the requirements. Further information about the REVLIMID REMS program is available at www.celgeneriskmanagement.com or by telephone at 1-888-423-5436

Hematologic Toxicity: REVLIMID can cause significant neutropenia and thrombocytopenia. Monitor patients with neutropenia for signs of infection. Advise patients to observe for bleeding or bruising, especially with use of concomitant medications that may increase risk of bleeding. MM: Patients taking REVLIMID/dex should have their complete blood counts (CBC) assessed every 7 days for the first 2 cycles, on days 1 and 15 of cycle 3, and every 28 days thereafter. MCL: Patients taking REVLIMID for MCL should have their CBCs monitored weekly for the first cycle (28 days), every 2 weeks during cycles 2-4, and then monthly thereafter. Patients may require dose interruption and/or dose reduction. MDS: See Boxed WARNINGS

Venous and Arterial Thromboembolism: Venous thromboembolic events (DVT and PE) and arterial thromboses are increased in patients treated with REVLIMID. A significantly increased risk of DVT (7.4%) and PE (3.7%) occurred in patients with MM after at least one prior therapy, treated with REVLIMID/dex compared to placebo/dex (3.1% and 0.9%) in clinical trials with varying use of anticoagulant therapies. In NDMM study, in which nearly all patients received antithrombotic prophylaxis, DVT (3.6%) and PE (3.8%) were reported in the Rd continuous arm. Myocardial infarction (MI,1.7%) and stroke (CVA,2.3%) are increased in patients with MM after at least 1 prior therapy who were treated with REVLIMID/dex therapy compared with placebo/dex (0.6%, and 0.9%) in clinical trials. In NDMM study, MI (including acute) was reported (2.3%) in the Rd Continuous arm. Frequency of serious adverse reactions of CVA was (0.8%) in the Rd Continuous arm. Patients with known risk factors, including prior thrombosis, may be at greater risk and actions should be taken to try to minimize all modifiable factors (e.g. hyperlipidemia, hypertension, smoking). In controlled clinical trials that did not use concomitant thromboprophylaxis, 21.5% overall thrombotic events occurred in patients with refractory and relapsed MM who were treated with REVLIMID/dex compared to 8.3% thrombosis in the placebo/dex group. Median time to first thrombosis event was 2.8 months. In NDMM study, which nearly all patients received antithrombotic prophylaxis, overall frequency of thrombotic events was 17.4% in combined Rd continuous and Rd18 arms. Median time to first thrombosis event as 4.37 months. Thromboprophylaxis is recommended and regimen is based on patients underlying risks. ESAs and estrogens may further increase the risk of thrombosis and their use should be based on a benefit-risk decision. See Boxed WARNINGS

Increased Mortality in Patients With CLL: In a clinical trial in the first line treatment of patients with CLL, single agent REVLIMID therapy increased the risk of death as compared to single agent chlorambucil. In an interim analysis, there were 34 deaths among 210 patients on the REVLIMID treatment arm compared to 18 deaths among 211 patients in the chlorambucil treatment arm, and hazard ratio for overall survival was 1.92 [95% CI: 1.08-3.41] consistent with a 92% increase in risk of death. Serious adverse cardiovascular reactions, including atrial fibrillation, myocardial infarction, and cardiac failure occurred more frequently in the REVLIMID treatment arm. REVLIMID is not indicated and not recommended for use in CLL outside of controlled clinical trials

Second Primary Malignancies: In clinical trials in patients with MM receiving REVLIMID, an increase of invasive second primary malignancies notably AML and MDS have been observed. The increase of AML and MDS occurred predominantly in NDMM patients receiving REVLIMID in combination with oral melphalan (5.3%) or immediately following high dose intravenous melphalan and ASCT (up to 5.2%). The frequency of AML and MDS cases in the Revlimid/dex arms was observed to be 0.4%. Cases of B-cell malignancies (including Hodgkin’s Lymphomas) were observed in clinical trials where patients received lenalidomide in the post-ASCT setting. Patients who received REVLIMID-containing therapy until disease progression did not show a higher incidence of invasive SPM than patients treated in the fixed duration REVLIMID-containing arms. Monitor patients for the development of second primary malignancies. Take into account both the potential benefit and risk of second primary malignancies when considering treatment with REVLIMID

Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with lenalidomide in combination with dex. The mechanism of drug-induced hepatotoxicity is unknown. Pre-existing viral liver disease, elevated baseline liver enzymes, and concomitant medications may be risk factors. Monitor liver enzymes periodically. Stop REVLIMID upon elevation of liver enzymes.

After return to baseline values, treatment at a lower dose may be considered

Allergic Reactions: Angioedema and serious dermatologic reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported. These events can be fatal. Patients with a prior history of Grade 4 rash associated with thalidomide treatment should not receive REVLIMID. REVLIMID interruption or discontinuation should be considered for Grade 2-3 skin rash. REVLIMID must be discontinued for angioedema, Grade 4 rash, exfoliative or bullous rash, or if SJS or TEN is suspected and should not be resumed following discontinuation for these reactions. REVLIMID capsules contain lactose. Risk-benefit of REVLIMID treatment should be evaluated in patients with lactose intolerance

Tumor Lysis Syndrome: Fatal instances of tumor lysis syndrome (TLS) have been reported during treatment with lenalidomide. The patients at risk of TLS are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken

Tumor Flare Reaction: Tumor flare reaction (TFR) has occurred during investigational use of lenalidomide for CLL and lymphoma, and is characterized by tender lymph node swelling, low grade fever, pain and rash.

Monitoring and evaluation for TFR is recommended in patients with MCL. Tumor flare may mimic the progression of disease (PD). In patients with Grade 3 or 4 TFR, it is recommended to withhold treatment with lenalidomide until TFR resolves to ≤ Grade 1. In the MCL trial, approximately 10% of subjects experienced TFR; all reports were Grade 1 or 2 in severity. All of the events occurred in cycle 1 and one patient developed TFR again in cycle 11. Lenalidomide may be continued in patients with Grade 1 and 2 TFR without interruption or modification, at the physician’s discretion. Patients with Grade 1 or 2 TFR may also be treated with corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and/or narcotic analgesics for management of TFR symptoms. Patients with Grade 3 or 4 TFR may be treated for management of symptoms per the guidance for treatment of Grade 1 and 2 TFR

Impaired Stem Cell Mobilization: A decrease in the number of CD34+ cells collected after treatment ( > 4 cycles) with REVLIMID has been reported. In patients who are autologous stem cell transplant (ASCT) candidates, referral to a transplant center should occur early in treatment to optimize timing of the stem cell collection.

ADVERSE REACTIONS

Multiple Myeloma

In newly diagnosed patients the most frequently reported Grade 3 or 4 adverse reactions in Arm Rd Continuous included neutropenia (27.8%), anemia (18.2%), thrombocytopenia (8.3%), pneumonia (11.1%), asthenia (7.7.%), fatigue (7.3%), back pain (7%), hypokalemia (6.6%), rash (7.3%), cataract (5.8%), dyspnea (5.6%), DVT (5.5%), hyperglycemia (5.3%), lymphopenia and leukopenia. The frequency of infections in Arm Rd Continuous was 75%

Adverse reactions reported in ≥20% of NDMM patients in Arm Rd Continuous: diarrhea (45.5%), anemia (43.8%), neutropenia (35%), fatigue (32.5%), back pain (32%), insomnia (27.6%), asthenia (28.2%), rash (26.1%), decreased appetite (23.1%), cough (22.7%), pyrexia (21.4%), muscle spasms (20.5%), and abdominal pain (20.5%). The frequency of onset of cataracts increased over time with 0.7% during the first 6 months and up to 9.6% by the second year of treatment with Arm Rd
Continuous

After at least one prior therapy most adverse reactions and Grade 3/4 adverse reactions were more frequent in MM patients who received the combination of REVLIMID/dex compared to placebo/dex. Grade 3 or 4 adverse reactions included neutropenia 33.4% vs 3.4%, febrile neutropenia 2.3% vs 0%, DVT 8.2% vs 3.4% and PE 4% vs 0.9% respectively
Adverse reactions reported in ≥15% of MM patients (REVLIMID/dex vs dex/placebo): fatigue (44% vs 42%), neutropenia (42% vs 6%), constipation (41% vs 21%), diarrhea (39% vs 27%), muscle cramp (33% vs 21%), anemia (31% vs 24%), pyrexia (28% vs 23%), peripheral edema (26% vs 21%), nausea (26% vs 21%), back pain (26% vs 19%), upper respiratory tract infection (25% vs 16%), dyspnea (24% vs 17%), dizziness (23% vs 17%), thrombocytopenia (22% vs 11%), rash (21% vs 9%), tremor (21% vs 7%), weight decreased (20% vs 15%), nasopharyngitis (18% vs 9%), blurred vision (17% vs 11%), anorexia (16% vs 10%), and dysgeusia (15% vs 10%)

Myelodysplastic Syndromes

Grade 3 and 4 adverse events reported in ≥ 5% of patients with del 5q MDS were neutropenia (53%), thrombocytopenia (50%), pneumonia (7%), rash (7%), anemia (6%), leukopenia (5%), fatigue (5%), dyspnea (5%), and back pain (5%)
Adverse events reported in ≥15% of del 5q MDS patients (REVLIMID): thrombocytopenia (61.5%), neutropenia (58.8%), diarrhea (49%), pruritus (42%), rash (36%), fatigue (31%), constipation (24%), nausea (24%), nasopharyngitis (23%), arthralgia (22%), pyrexia (21%), back pain (21%), peripheral edema (20%), cough (20%), dizziness (20%), headache (20%), muscle cramp (18%), dyspnea (17%), pharyngitis (16%), epistaxis (15%), asthenia (15%), upper respiratory tract infection (15%)

Mantle Cell Lymphoma

Grade 3 and 4 adverse events reported in ≥5% of patients treated with REVLIMID in the MCL trial (N=134) included neutropenia (43%), thrombocytopenia (28%), anemia (11%), pneumonia (9%), leukopenia (7%), fatigue (7%), diarrhea (6%), dyspnea (6%), and febrile neutropenia (6%)

Serious adverse events reported in ≥2 patients treated with REVLIMID monotherapy for MCL included chronic obstructive pulmonary disease, clostridium difficile colitis, sepsis, basal cell carcinoma, and supraventricular tachycardia
Adverse events reported in ≥15% of patients treated with REVLIMID in the MCL trial included neutropenia (49%), thrombocytopenia (36%), fatigue (34%), anemia (31%), diarrhea (31%), nausea (30%), cough (28%), pyrexia (23%), rash (22%), dyspnea (18%), pruritus (17%), peripheral edema (16%), constipation (16%), and leukopenia (15%)

DRUG INTERACTIONS

Periodic monitoring of digoxin plasma levels, in accordance with clinical judgment and based on standard clinical practice in patients receiving this medication, is recommended during administration of REVLIMID. It is not known whether there is an interaction between dex and warfarin. Close monitoring of PT and INR is recommended in MM patients taking concomitant warfarin. Erythropoietic agents, or other agents, that may increase the risk of thrombosis, such as estrogen containing therapies, should be used with caution after making a benefit-risk assessment in patients receiving REVLIMID

USE IN SPECIFIC POPULATIONS

Pregnancy: If pregnancy does occur during treatment, immediately discontinue the drug. Under these conditions, refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Any suspected fetal exposure to REVLIMID must be reported to the FDA via the MedWatch program at 1-800-332-1088 and also to Celgene Corporation at 1-888-423-5436

Nursing Mothers: It is not known whether REVLIMID is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother

Pediatric Use: Safety and effectiveness in patients below the age of 18 have not been established

Renal Impairment: Since REVLIMID is primarily excreted unchanged by the kidney, adjustments to the starting dose of REVLIMID are recommended to provide appropriate drug exposure in patients with moderate (CLcr 30-60 mL/min) or severe renal impairment (CLcr < 30 mL/min) and in patients on dialysis

Please see accompanying full Prescribing Information, including Boxed WARNINGS.

About SWOG is a publicly funded worldwide network of researchers that design and conduct cancer clinical trials. The group’s goal is to change medical practice so it improves the lives of people with cancer. SWOG trials test new ways to diagnose, treat, and prevent cancer. SWOG researchers also study ways to improve the care cancer patients receive, and improve quality of life for both patients and survivors. The approximately 6,000 physician-researchers in the network practice at more than 950 institutions nationwide, including 32 NCI-designated cancer centers, as well as cancer centers in six other countries. Formerly the Southwest Oncology Group, SWOG is part of the NCI’s National Clinical Trials Network and is supported primarily through NCI research funding. The group is headquartered at the Knight Cancer Institute at Oregon Health & Science University in Portland, Oregon, has an operations office in San Antonio, Texas, and has a statistical center in Seattle, Washington. Learn more at swog.org.

On December 5, 2015 Amgen (NASDAQ:AMGN) reported that The Lancet Oncology published results from the pivotal Phase 3 head-to-head ENDEAVOR study comparing Kyprolis (carfilzomib) plus dexamethasone to Velcade (bortezomib) plus dexamethasone in patients with relapsed multiple myeloma (Press release, Amgen, DEC 5, 2015, View Source;p=RssLanding&cat=news&id=2120388 [SID:1234508408]). The data showed that patients treated with Kyprolis plus dexamethasone achieved progression-free survival (PFS) of 18.7 months compared to 9.4 months in those receiving bortezomib plus dexamethasone (HR=0.53; 95 percent CI: 0.44,0.65 p<0.0001), a current standard of care in relapsed multiple myeloma.

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These findings demonstrate that patients with relapsed multiple myeloma treated with Kyprolis lived twice as long without disease worsening as those treated with bortezomib. The most common adverse events (greater than 25 percent) in the Kyprolis arm were diarrhea, anemia, fatigue, dyspnea, pyrexia and insomnia. Treatment discontinuation due to adverse events and on-study deaths were comparable between the two arms.

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"In this head-to-head comparison, carfilzomib plus dexamethasone resulted in a twofold decrease in the risk of progression or death, compared with bortezomib plus dexamethasone, a result that was consistent regardless of age or prior bortezomib exposure," said study co-author and investigator, Meletios A. Dimopoulos, M.D., professor of Clinical Therapeutics at the National and Kapodistrian University of Athens, School of Medicine. "For patients with multiple myeloma, these results are clinically meaningful and translate to more than nine months without disease progression."

"Coupled with results previously seen in the ASPIRE pivotal trial, data from the ENDEAVOR study support the use of Kyprolis as a backbone therapy for the management of relapsed multiple myeloma, a difficult-to-treat blood cancer," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "This is an important publication because it provides clinical evidence of Kyprolis’ potential to extend the time patients live without their disease progressing and improve the depth and duration of a response."

Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse, and while new therapies have become available, a significant unmet need still remains for patients no longer responding to treatment.1,2 Multiple myeloma is an orphan disease and accounts for approximately one percent of all cancers.3,4

Regulatory Status
Data from the ENDEAVOR study are the basis of the supplemental New Drug Application (sNDA) of Kyprolis in combination with dexamethasone for patients with relapsed multiple myeloma. The sNDA was accepted Sept.19, 2015, for priority review by the U.S. Food and Drug Administration (FDA) and the Prescription Drug User Fee Act (PDUFA) target action date is Jan. 22, 2016. Priority review is assigned to applications for drugs that treat serious conditions and would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions. Amgen also just announced submission of the ENDEAVOR data to the European Commission for potential authorization of Kyprolis in combination with dexamethasone in the European Union.

About ENDEAVOR
The randomized ENDEAVOR (RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma) trial of 929 patients evaluated Kyprolis in combination with low-dose dexamethasone, versus bortezomib with low-dose dexamethasone in patients whose multiple myeloma has relapsed after at least one, but not more than three prior therapeutic regimens. The primary endpoint of the trial was PFS, defined as the time from treatment initiation to disease progression or death. In a clinical trial, measuring the PFS is one way to demonstrate how well a treatment works.5

The superiority of the Kyprolis combination compared to the bortezomib combination with respect to PFS was seen across all pre-specified subgroups, including Velcade-naïve patients, those with high- or standard-risk cytogenetics and with or without prior transplantation. The Kyprolis combination also demonstrated superiority over the bortezomib combination for secondary endpoints, achieving a higher overall response rate (76.9 percent vs. 62.6 percent; p<0.0001) and lower rate of grade 2 or higher neuropathy events (6 percent vs. 32 percent; p<0.0001). Treatment with the Kyprolis combination resulted in a two-fold increase in the median duration of response (21.3 months) compared to the bortezomib combination (10.4 months).

In the Kyprolis and bortezomib groups, 54.3 percent and 28.6 percent of patients achieved a very good partial response or better (p<0.0001), and 12.5 percent and 6.2 percent of patients achieved a complete response or better (p<0.0001), respectively. Overall survival data are not yet mature and continue to be monitored.

Treatment discontinuation due to adverse events and on-study deaths were comparable between the two arms. A number of known adverse drug reactions were reported at a higher rate in the Kyprolis group compared with the bortezomib group, including any-grade dyspnea, hypertension, pyrexia, and cough (preferred terms) as were any-grade cardiac failure (grouped term; 8.2 percent vs. 2.9 percent) and acute renal failure (grouped term; 8.2 percent vs. 4.8 percent). However, the rates of cardiac and renal failure for Kyprolis were comparable to those observed in the previous Phase 3 ASPIRE study.

Rates of grade 3 or higher adverse events were 73.2 percent in the Kyprolis group and 66.9 percent in the bortezomib group. Grade 3 or higher adverse events of interest in the Kyprolis and bortezomib groups included hypertension (preferred term; 8.9 percent vs. 2.6 percent), dyspnea (preferred term; 5.4 percent vs. 2.2 percent), cardiac failure (grouped term; 4.7 percent vs. 1.8 percent), acute renal failure (grouped term; 4.0 percent vs. 2.6 percent), ischemic heart disease (grouped term; 1.7 percent vs. 1.6 percent) and pulmonary hypertension (grouped term; 0.6 percent vs. 0.2 percent).

Patients received treatment until progression with Kyprolis as a 30-minute infusion on days 1, 2, 8, 9, 15 and 16 of 28 day treatment cycles, along with low-dose dexamethasone (20 mg). For Cycle 1 only, Kyprolis was administered at 20 mg/m2 on days 1 and 2, followed by escalation to 56 mg/m2 from day 8. Patients who tolerated 56 mg/m2 in Cycle 1 were kept at this dose for subsequent cycles. Patients who received bortezomib (1.3 mg/m2) with low-dose dexamethasone (20 mg) were administered bortezomib subcutaneously or intravenously at the discretion of the investigator and in accordance with regulatory approval of bortezomib. More than 75 percent of the patients in the control arm received bortezomib subcutaneously. This study was conducted at 235 sites worldwide. For information about this trial, please visit www.clinicaltrials.gov under trial identification number NCT01568866.

Amgen Webcast Investor Meeting
Amgen will host a webcast investor meeting at the 57th Anuual American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting on Monday, Dec. 7, 2015, at 7 p.m. ET. Sean E. Harper, M.D., executive vice president of Research and Development at Amgen, along with members of Amgen’s clinical development team and clinical investigators will participate to discuss data presented at ASH (Free ASH Whitepaper) and Amgen’s broader oncology portfolio of products.

Live audio of the conference call will be simultaneously broadcast over the Internet and will be available to members of the news media, investors and the general public.

The webcast, as with other selected presentations regarding developments in Amgen’s business given by management at certain investor and medical conferences, can be found on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

About Kyprolis (carfilzomib) for Injection
Kyprolis is an irreversible proteasome inhibitor for use in the treatment of patients with relapsed multiple myeloma.2 Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.6 Kyprolis has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.7 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.7 The irreversibility of Kyprolis’ binding has also been shown to offer a more sustained inhibition of the targeted enzymes.8

Kyprolis is currently approved in the U.S. in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior lines of therapy.

Kyprolis is also indicated under FDA accelerated approval as a single agent for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval is based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified.

Kyprolis is also approved in Argentina, Israel, Kuwait, Mexico, Thailand, Colombia 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 about Kyprolis, visit www.kyprolis.com.

Important Safety Information Regarding Kyprolis (carfilzomib) for Injection U.S. Indication

Cardiac Toxicities
New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, and decreased ejection fraction), restrictive cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of Kyprolis. Death due to cardiac arrest has occurred within a day of Kyprolis administration.

Withhold Kyprolis for Grade 3 or 4 cardiac adverse events until recovery, and consider whether to restart Kyprolis based on a benefit/risk assessment.

Adequate hydration is required prior to each dose in Cycle 1. Monitor all patients for evidence of volume overload, especially patients at risk for cardiac failure. Adjust total fluid intake as clinically appropriate in patients with baseline cardiac failure or who are at risk for cardiac failure. Patients ≥ 75 years, the risk of cardiac failure is increased. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, and conduction abnormalities may be at greater risk for cardiac complications.

Acute Renal Failure
Cases of acute renal failure and renal insufficiency adverse events (renal impairment, acute renal failure, and renal failure) have occurred in patients receiving Kyprolis. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received Kyprolis monotherapy. This risk was greater in patients with a baseline reduced estimated creatinine clearance. Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate.

Tumor Lysis Syndrome
Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred in patients receiving Kyprolis. Patients with multiple myeloma and a high tumor burden should be considered at greater risk for TLS. Adequate hydration is required prior to each dose in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly. Withhold Kyprolis until TLS is resolved.

Pulmonary Toxicity
Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred in patients receiving Kyprolis. Some events have been fatal. In the event of drug-induced pulmonary toxicity, discontinue Kyprolis.

Pulmonary Hypertension
Pulmonary arterial hypertension (PAH) was reported in patients treated with Kyprolis. Evaluate with cardiac imaging and/or other tests as indicated. Withhold Kyprolis for PAH until resolved or returned to baseline and consider whether to restart Kyprolis based on a benefit/risk assessment.

Dyspnea
Dyspnea was reported in patients treated with Kyprolis. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Stop Kyprolis for Grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart Kyprolis based on a benefit/risk assessment.

Hypertension
Hypertension, including hypertensive crisis and hypertensive emergency, has been observed with Kyprolis. Some of these events have been fatal. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold Kyprolis and evaluate. Consider whether to restart Kyprolis based on a benefit/risk assessment.

Venous Thrombosis
Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed with Kyprolis. Thromboprophylaxis is recommended and should be based on an assessment of the patient’s underlying risks, treatment regimen, and clinical status.

Infusion Reactions
Infusion reactions, including life-threatening reactions, have occurred in patients receiving Kyprolis. Symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina. These reactions can occur immediately following or up to 24 hours after administration of Kyprolis. Premedicate with dexamethasone to reduce the incidence and severity of infusion reactions. Inform patients of the risk and of symptoms of an infusion reaction and to contact a physician immediately if they occur.

Thrombocytopenia
Kyprolis causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle. Thrombocytopenia was reported in patients receiving Kyprolis. Monitor platelet counts frequently during treatment with Kyprolis. Reduce or withhold dose as appropriate.

Hepatic Toxicity and Hepatic Failure
Cases of hepatic failure, including fatal cases, have been reported during treatment with Kyprolis. Kyprolis can cause increased serum transaminases. Monitor liver enzymes regularly. Reduce or withhold dose as appropriate.

Thrombotic Thrombocytopenic Purpura /Hemolytic Uremic Syndrome (TTP/HUS)
Cases of TTP/HUS including fatal outcome have occurred in patients receiving Kyprolis. Monitor for signs and symptoms of TTP/HUS. Discontinue Kyprolis if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded, Kyprolis may be restarted. The safety of reinitiating Kyprolis therapy in patients previously experiencing TTP/HUS is not known.

Posterior Reversible Encephalopathy Syndrome (PRES)
Cases of PRES have occurred in patients receiving Kyprolis. PRES was formerly known as Reversible Posterior Leukoencephalopathy Syndrome. Consider a neuro-radiological imaging (MRI) for onset of visual or neurological symptoms, such as seizure, headache, lethargy, confusion, blindness, altered consciousness, along with hypertension. Discontinue Kyprolis if PRES is suspected and evaluate. The safety of reinitiating Kyprolis therapy in patients previously experiencing PRES is not known.

Embryo-fetal Toxicity
Kyprolis can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals.

Females of reproductive potential should be advised to avoid becoming pregnant while being treated with Kyprolis and the potential hazard to the fetus if Kyprolis is used during pregnancy.

ADVERSE REACTIONS
The most common adverse events of any grade occurring in at least 20 percent of patients treated with Kyprolis in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, decreased platelets, dyspnea, diarrhea, decreased lymphocyte, headache, decreased hemoglobin, cough, edema peripheral.

The most common adverse events of any grade occurring in at least 20 percent of patients treated with Kyprolis in the combination therapy trial: decreased lymphocytes, decreased absolute neutrophil count, decreased phosphorus, anemia, neutropenia, decreased total white blood cell count, decreased platelets, diarrhea, fatigue, thrombocytopenia, pyrexia, muscle spasm, cough, upper respiratory tract infection, decreased hemoglobin, hypokalemia.

Full U.S. prescribing information is available at 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, dyspnoea, hypertension including hypertensive crises, acute renal failure, tumour lysis syndrome, infusion reactions, thrombocytopenia, hepatic toxicity, posterior reversible encephalopathy syndrome (PRES) and thrombotic thrombocytopenic purpura/haemolytic uremic syndrome (TTP/HUS). The most common side effects are anaemia, fatigue, diarrhoea, thrombocytopenia, nausea, pyrexia, dyspnoea, respiratory tract infection, cough and peripheral oedema.

On December 5, 2015 Celgene Corporation (NASDAQ:CELG) and Acceleron Pharma Inc. (NASDAQ:XLRN) reported preliminary results from an ongoing long-term Phase 2 extension study in patients with lower risk myelodysplastic syndromes (MDS) at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Acceleron Pharma, DEC 5, 2015, View Source [SID:1234508405]). Results highlighted in an oral presentation showed that patients with lower risk MDS treated with luspatercept in the long-term extension study achieved and maintained increased hemoglobin levels and transfusion independence. Celgene and Acceleron are jointly developing luspatercept.

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"These results for longer-term luspatercept treatment in lower risk MDS patients are very exciting," said Aristoteles Giagounidis, M.D., Ph.D., Head of the Department of Oncology, Haematology, and Palliative Care at Marien Hospital in Düsseldorf, Germany. "There is substantial unmet medical need for patients who do not respond or become refractory to treatment with erythropoiesis stimulating agents or who are considered ineligible to receive them. Luspatercept has shown very encouraging activity in these patients which provides the basis for the Phase 3 MEDALIST study."

Luspatercept Data Presented at ASH (Free ASH Whitepaper)

A total of 32 low- or intermediate-1 risk MDS patients were treated with luspatercept in this long-term 24-month open-label extension study. Luspatercept was administered subcutaneously once every 3 weeks at a starting dose level of 1.0 mg/kg. The dose level could be increased to 1.75 mg/kg. Of these 32 patients, 13 had a low transfusion burden ( < 4 units RBC/8 weeks) and 19 had a high transfusion burden (≥4 units RBC/8 weeks). 59% of patients had been treated previously with erythropoiesis stimulating agents (ESA) and 19% of patients had previously been treated with lenalidomide. 91% of the patients were ring sideroblast positive (more than 15% of erythroid cells in the bone marrow were ring sideroblasts).

Patients who were refractory or intolerant to prior ESA treatment

63% (12 of 19) of HTB and LTB patients with prior ESA treatment achieved an International Working Group (IWG) Hematologic Improvement Erythroid (HI-E) response of a reduction of ≥4 units RBC over 8 weeks or a hemoglobin increase ≥1.5 g/dL for ≥8 weeks during their luspatercept treatment period
50% (7 of 14) achieved transfusion independence

Patients who are considered ESA ineligible because they had elevated erythropoietin levels between 200 and 500 U/L

71% (5 of 7) achieved an HI-E response and 50% (2 of 4) achieved transfusion independence

High Transfusion Burden (HTB) Patients

68% (13 of 19) of the HTB patients achieved the IWG HI-E criteria of a reduction of ≥4 units RBC over 8 weeks
42% (8 of 19) of the HTB patients achieved transfusion independence for ≥8 weeks

Low Transfusion Burden (LTB) Patients

69% (9 of 13) of the LTB patients achieved the IWG HI-E response criteria of a hemoglobin increase ≥1.5 g/dL for ≥8 weeks
The mean increase in hemoglobin reached levels between 2.0 and 2.5 g/dL and was maintained for the 9 months for which data are available

Safety

Adverse events at least possibly related to study drug that occurred in patients during the extension study included bone pain, headache, hypotonia, myalgia and nausea. No serious or grade 3 or 4 adverse events related to study drug have been reported during the ongoing extension study.
Celgene and Acceleron are in the process of initiating a global Phase 3 study in low risk, ring sideroblast positive MDS patients.

Luspatercept is an investigational product that is not approved for any use in any country.

About Luspatercept

Luspatercept is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members in the Transforming Growth Factor-Beta (TGF-β) superfamily involved in the late stages of erythropoiesis (red blood cell production). Luspatercept regulates late-stage erythrocyte (red blood cell) precursor cell differentiation and maturation. This mechanism of action is distinct from that of erythropoietin (EPO), which stimulates the proliferation of early-stage erythrocyte precursor cells. Acceleron and Celgene are jointly developing luspatercept as part of a global collaboration. For more information, please visit www.clinicaltrials.gov.