On November 1, 2018 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported that the European Commission (EC) has approved the type-II variation application for VENCLYXTO (venetoclax) in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) who have received at least one prior therapy (Press release, AbbVie, NOV 1, 2018, View Source [SID1234530458]). This approval allows more patients to receive VENCLYXTO in the second-line setting and gives healthcare providers the ability to prescribe this medicine to a broader population of patients with R/R CLL than the previously approved indication for VENCLYXTO as monotherapy in the European Union (EU). The approval is valid in all 28 member states of the EU, as well as Iceland, Liechtenstein and Norway.

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The EC approval is based on results from the MURANO Phase 3 randomized clinical trial, which evaluated the efficacy and safety of VENCLYXTO in combination with rituximab compared to bendamustine in combination with rituximab, an established standard of care chemoimmunotherapy regimen for patients with R/R CLL.1 At the time of the primary analysis, the trial demonstrated a statistically significant improvement in investigator-assessed progression-free survival (PFS; the time on treatment without disease progression or death2) in patients who received VENCLYXTO plus rituximab, resulting in an 83 percent reduction in the risk of disease progression or death (hazard ratio [HR]:0.17; 95% confidence interval [CI]: 0.11-0.25; P<0.0001) and prolonged overall survival (OS) compared to the standard of care chemoimmunotherapy (HR: 0.48; 95% CI: 0.25-0.90; overall survival data are not yet mature).1

In the MURANO Phase 3 clinical trial, undetectable minimal residual disease (uMRD) was a secondary endpoint assessed at the end of combination therapy (nine-month assessment1,3). The majority of patients in the trial who received VENCLYXTO plus rituximab achieved uMRD in the peripheral blood, with 62.4 percent of patients achieving uMRD versus 13.3 percent with bendamustine in combination with rituximab.1 uMRD is an objective measure defined as the presence of less than one CLL cell in 10,000 white blood cells remaining in the blood or bone marrow following treatment.2 Earlier prospective clinical trials have provided evidence that achieving uMRD in CLL patients is associated with improved clinical outcomes.2

"Chronic lymphocytic leukemia can relapse and become refractory to first-line treatment, and there is a need for better therapies to treat these patients who otherwise have limited options," said Prof. John Seymour, MBBS, Ph.D., lead investigator of the MURANO trial and Director of Cancer Medicine at the Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Australia. "The venetoclax plus rituximab combination provides these patients with an alternative treatment option that is superior to a type of chemoimmunotherapy and can achieve deep responses, as shown by MRD negativity rates in the peripheral blood and bone marrow, allowing for a fixed duration of treatment without the need for chemoimmunotherapy."

CLL is a slow-growing form of leukemia, or blood cancer, in which too many immature lymphocytes (a type of white blood cell) are found predominantly in the blood and bone marrow.4 CLL accounts for approximately one third of new leukemia diagnoses.5

In September 2018, AbbVie announced the European Committee for Medicinal Products for Human Use (CHMP) granted a positive opinion for the Marketing Authorization Application for VENCLYXTO plus rituximab for the treatment of patients with R/R CLL.

"The approval of VENCLYXTO in combination with rituximab is an important step forward in providing patients with relapsed/refractory chronic lymphocytic leukemia a strong chance to live longer without their disease progressing," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "We look forward to bringing VENCLYXTO to more patients with chronic lymphocytic leukemia, while continuing to further the research and development of therapies with the potential to transform the standards of care in blood cancers."

VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

About the MURANO Trial
A total of 389 patients with R/R CLL who had received at least one prior therapy were enrolled in the international, multicenter, open-label, randomized Phase 3 MURANO trial. The trial was designed to evaluate the efficacy and safety of VENCLYXTO in combination with rituximab (N=194) compared with bendamustine in combination with rituximab (N=195). The median age of patients in the trial was 65 years (range: 22-85).1

The primary efficacy endpoint was investigator (INV)-assessed PFS. Median PFS with VENCLYXTO in combination with rituximab was not reached compared with 17.0 months for bendamustine in combination with rituximab (HR: 0.17; 95% CI: 0.11-0.25; P<0.0001). The median follow-up was 23.8 months (range: 0.0 to 37.4). Additional efficacy endpoints included independent review committee (IRC)-assessed PFS, INV- and IRC-assessed overall response rate (defined as complete response + complete response with incomplete marrow recovery + partial response + nodular partial response), overall survival and rates of uMRD.1

The safety profile of the combination of VENCLYXTO plus rituximab is consistent with the known safety profile of each of the medicines alone. The most common adverse reactions (ARs; ≥20 percent) of any grade for VENCLYXTO in combination with rituximab were neutropenia, diarrhea and upper respiratory tract infection. In the VENCLYXTO in combination with rituximab arm due to any AR, discontinuation occurred in 16 percent of patients, dose reduction in 15 percent, and dose interruption in 71 percent. In the VENCLYXTO in combination with rituximab arm, neutropenia led to dose interruption of VENCLYXTO in 43 percent of patients and discontinuation in 3 percent. The most serious ARs (≥2 percent) for VENCLYXTO in combination with rituximab or VENCLYXTO monotherapy were pneumonia, febrile neutropenia and tumor lysis syndrome.1

About VENCLYXTO (venetoclax)
VENCLEXTA (VENCLYXTO in the EU) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other cancerous tumors, BCL-2 builds up and prevents cancer cells from undergoing their natural death or self-destruction process, which is called apoptosis. VENCLEXTA/VENCLYXTO targets the BCL-2 protein and works to restore the process of apoptosis.

VENCLEXTA/VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research and to studying venetoclax in clinical trials across several blood and other cancers.

VENCLEXTA/VENCLYXTO is approved in more than 50 countries, including the U.S. AbbVie and Roche are currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.

Important VENCLYXTO (venetoclax) EU Safety Information3

Contraindications
Hypersensitivity to the active substance or to any of the excipients is contraindicated. Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase due to increased risk for tumor lysis syndrome (TLS). Concomitant use of preparations containing St. John’s wort as VENCLYXTO efficacy may be reduced.

Special Warnings & Precautions for Use
Tumor lysis syndrome (TLS), including fatal events, has occurred in patients with previously treated CLL with high tumor burden when treated with VENCLYXTO. VENCLYXTO poses a risk for TLS in the initial 5-week dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLYXTO and at each dose increase. Patients should be assessed for risk and should receive appropriate prophylaxis, monitoring, and management for TLS.

Neutropenia (grade 3 or 4) has been reported and complete blood counts should be monitored throughout the treatment period. Serious infections including events of sepsis with fatal outcome have been reported. Supportive measures including antimicrobials for any signs of infection should be considered.

Live vaccines should not be administered during treatment or thereafter until B-cell recovery.

Drug Interactions
CYP3A inhibitors may increase VENCLYXTO plasma concentrations. At initiation and dose-titration phase: Strong CYP3A inhibitors are contraindicated due to increased risk for TLS and moderate CYP3A inhibitors should be avoided. If moderate CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations. At steady daily dose: If moderate or strong CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations.

Avoid concomitant use of P-gp and BCRP inhibitors at initiation and during the dose-titration phase.

CYP3A4 inducers may decrease VENCLYXTO plasma concentrations. Avoid coadministration with strong or moderate CYP3A inducers. These agents may decrease venetoclax plasma concentrations.

Co-administration of bile acid sequestrants with VENCLYXTO is not recommended as this may reduce the absorption of VENCLYXTO.

Adverse Reactions
The most commonly occurring adverse reactions (>=20%) of any grade in patients receiving venetoclax in the combination study with rituximab were neutropenia, diarrhea, and upper respiratory tract infection. In the monotherapy studies, the most common adverse reactions were neutropenia/neutrophil count decreased, diarrhea, nausea, anemia, fatigue, and upper respiratory tract infection.

The most frequently occurring serious adverse reactions (>=2%) in patients receiving venetoclax in combination with rituximab or as monotherapy were pneumonia, febrile neutropenia and TLS.

Discontinuation due to adverse reactions occurred in 16% of patients receiving venetoclax plus rituximab and 9% receiving venetoclax monotherapy. Dosage adjustments due to adverse reactions occurred in 15% of patients receiving venetoclax plus rituximab and 2% receiving venetoclax monotherapy. Dose interruptions occurred in 71% of patients treated with the combination of venetoclax and rituximab.

Specific Populations
Patients with reduced renal function (CrCl <80 mL/min) may require more intensive prophylaxis and monitoring to reduce the risk of TLS. Safety in patients with severe renal impairment (CrCl <30 mL/min) or on dialysis has not been established, and a recommended dose for these patients has not been determined. VENCLYXTO should be administered to patients with severe renal impairment only if the benefit outweighs the risk and patients should be monitored closely for signs of toxicity due to increased risk of TLS.

VENCLYXTO may cause embryo-fetal harm when administered to a pregnant woman. Advise nursing women to discontinue breastfeeding during treatment.

On November 1, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported that updated data from its isocitrate dehydrogenase (IDH) programs and pyruvate kinase (PK) deficiency program will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held December 1 – 4, 2018 in San Diego (Press release, Agios Pharmaceuticals, NOV 1, 2018, View Source [SID1234530488]).

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In total, five abstracts led by Agios describing updated data from the company’s IDH programs and PKD program have been accepted for presentation at ASH (Free ASH Whitepaper).

The accepted abstracts are listed below and are available online on the ASH (Free ASH Whitepaper) conference website: View Source

Oral presentations by Agios:

Title: Ivosidenib (AG-120) Induced Durable Remissions and Transfusion Independence in Patients with IDH1-Mutant Untreated AML: Results from a Phase 1 Dose Escalation and Expansion Study
Date & Time: Monday December 3, 2018 at 7:30 a.m. PST
Oral Abstract Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Targeted Therapy
Abstract: 561
Location: Manchester Grand Hyatt San Diego, Seaport Ballroom F
Presenter: Gail J. Roboz, M.D., Weill Cornell Medical College

Title: Ivosidenib or Enasidenib Combined with Induction and Consolidation Chemotherapy in Patients with Newly Diagnosed AML with an IDH1 or IDH2 Mutation is Safe, Effective, and Leads to MRD-Negative Complete Remissions
Date & Time: Monday December 3, 2018 at 7:15 a.m. PST
Oral Abstract Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Targeted Therapy
Abstract: 560
Location: Manchester Grand Hyatt San Diego, Seaport Ballroom F
Presenter: Eytan Stein, M.D., Memorial Sloan Kettering Cancer Center

Poster presentations by Agios:

Title: Ivosidenib (AG-120) Induced Durable Remissions and Transfusion Independence in Patients with IDH1-Mutant Relapsed or Refractory Myelodysplastic Syndrome: Results from a Phase 1 Dose Escalation and Expansion Study
Poster Session Date & Time: Saturday December 1, 2018 from 6:15-8:15 p.m. PST
Poster Session: 637. Myelodysplastic Syndromes—Clinical Studies: Poster I
Abstract: 1812
Poster Location: San Diego Convention Center, Hall GH
Author: Courtney Denton DiNardo, M.D., University of Texas MD Anderson Cancer Center

Title: Population Pharmacokinetics of Ivosidenib (AG-120) in Patients with IDH1-Mutant Advanced Hematologic Malignancies
Poster Session Date & Time: Saturday December 1, 2018 from 6:15-8:15 p.m. PST
Poster Session: 613. Acute Myeloid Leukemia: Clinical Studies: Poster I
Abstract: 1394
Poster Location: San Diego Convention Center, Hall GH
Author: Kha Le, Ph.D., Agios Pharmaceuticals

Title: Genotype-Response Correlation in DRIVE PK, a Phase 2 Study of AG-348 in Patients with Pyruvate Kinase Deficiency
Poster Session Date & Time: Monday December 3, 2018 from 6:00-8:00 p.m. PST
Poster Session: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III
Abstract: 3621
Poster Location: San Diego Convention Center, Hall GH
Author: Charles Kung, Ph.D., Agios Pharmaceuticals

On November 1, 2018 Celgene Corporation (NASDAQ:CELG) reported that data from more than 100 abstracts, including a study being featured as a plenary presentation and more than 40 selected for oral presentations, evaluating Celgene investigational agents and investigational uses of marketed products will be presented at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting between Dec. 1-4 in San Diego, CA (Press release, Celgene, NOV 1, 2018, View Source [SID1234530504]).

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"Celgene is deeply committed to furthering our understanding of blood cancers and encouraged by the promise of new innovations to improve or extend the lives of patients living with these intractable diseases," said Dr. Alise Reicin, President, Global Clinical Development for Celgene. "Importantly, this year’s ASH (Free ASH Whitepaper) data highlight the advancement of Celgene’s pipeline including first-in-class compounds with the potential to transform treatment across multiple blood cancers."

Presentations will include data from Celgene investigational agents in company-sponsored or investigator-initiated clinical studies across the company’s approved and investigational portfolio. Abstracts highlight some of the first results of key pivotal data for the company’s pipeline assets, illustrating the breadth and potential of the hematology portfolio. Of note, a first look at the results from the MEDALIST trial in patients with myelodysplastic syndrome (MDS) will be presented during the Plenary Scientific Session, which honors the top six research papers submitted for presentation at the meeting. Experts will also share results from key approved therapies and investigational CAR T cell therapies in non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, beta thalassemia and multiple myeloma.

Key presentations include:

First data of the pivotal, Phase 3, MEDALIST trial featured in the Plenary Scientific Sessions, highlighting the potential of luspatercept to address a significant unmet need in patients with MDS;
First data of the pivotal, Phase 3, BELIEVE trial highlighting the potential for luspatercept to address a significant unmet need in adult patients with beta thalassemia;
Data from the phase 1/2 TRANSCEND CLL-004 trial evaluating liso-cel (JCAR017) in patients with relapsed and/or refractory chronic lymphocytic leukemia (CLL);
Initial results from a phase 1 trial of bb21217, a next-generation anti-BCMA CAR T therapy, in patients with relapsed and/or refractory multiple myeloma (RRMM);
Data from the phase 1/2 EVOLVE trial evaluating JCARH125 in patients with RRMM; and
First data from the Phase 3, AUGMENT trial, a chemotherapy-free regimen of REVLIMIDplus rituximab (R2) in patients with relapsed and/or refractory indolent non-Hodgkin’s lymphoma.
Selected abstracts include*:

Plenary Session

Abstract #1: Plenary; Sunday, Dec. 2, 2:00 p.m., Hall AB, The MEDALIST Trial: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled, Randomized Study of Luspatercept to Treat Anemia in Patients with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions (List)

Beta Thalassemia

Abstract #163; Oral; Saturday, Dec. 1, 2:00 p.m., Room 30D, The BELIEVE Trial: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled, Study of Luspatercept in Adult Beta-Thalassemia Patients Who Require Regular Red Blood Cell (RBC) Transfusions (Cappellini)

Myeloid Diseases

New data findings evaluate Celgene in-line and investigational therapies in myeloid diseases.

Abstract #835; Oral; Monday, Dec. 3, 2:45 p.m., Room 25B, Real-World Treatment Patterns and Comparative Effectiveness Among a Population of Elderly Patients with Acute Myeloid Leukemia (AML) (Medeiros)

Abstract #4731; Poster; Monday, Dec. 3, 6:00 p.m., Hall GH, Factors Associated with Early Therapy Initiation in Patients (Pts) with Myelodysplastic Syndromes (MDS) in the Connect MDS/AML Disease Registry (Cogle)

Chimeric Antigen Receptor T-cell therapy (CAR T)

New data highlight growing base of research in cellular immunotherapy across multiple blood cancers.

Abstract #319; Oral; Sunday, Dec. 2, 7:30 a.m., Room 25B, Estimation of the Resource Utilization and Costs of Cytokine Release Syndrome Observed in the TRANSCEND-NHL Clinical Trial: A Micro-Costing Study (Siddiqi)

Abstract #300; Oral; Sunday, Dec. 2, 8:45 a.m., Marriott Marquis San Diego Marina, Pacific Ballroom 20, Rapid MRD-negative Responses in Patients with Relapsed/Refractory CLL Treated with Liso-cel, a CD-19-directed CAR T-cell Product: Preliminary Results from TRANSCEND CLL 004, a Phase 1/2 Study Including Patients with High-Risk Disease Previously Treated with Ibrutinib (Siddiqi)

Abstract #488; Oral; Sunday, Dec. 2, 4:45 p.m., Room 6B, Initial results from a phase 1 clinical study of bb21217, a next-generation anti-BCMA CAR T therapy (Shah)

Abstract #957; Oral; Monday, Dec. 3, 5:00 p.m., Ballroom 20A, JCARH125, Anti-BCMA CAR T-cell Therapy for Relapsed/Refractory Multiple Myeloma: Initial Proof of Concept Results from a Phase 1/2 Multicenter Study (EVOLVE) (Mailankody)

Lymphoma/Chronic Lymphocytic Leukemia (CLL)

Multiple studies evaluate novel chemotherapy-free combinations in lymphoma and chronic lymphocytic leukemia.

Abstract #445; Oral; Sunday, Dec. 2, 4:30 p.m., Hall AB, AUGMENT: A Phase III Randomized Study of Lenalidomide Plus Rituximab (R2) vs. Rituximab/Placebo in Patients with Relapsed/Refractory Indolent Non-Hodgkin’s Lymphoma (Leonard)

Abstract #446; Oral; Sunday, Dec. 2, 4:45 p.m., Hall AB, A Phase II LYSA Study of Obinutuzumab Combined with Lenalidomide for Advanced Front-Line Follicular B-Cell Lymphoma in Need of Systemic Therapy (Morschhauser)

Abstract #999; Oral; Monday, Dec. 3, 6:45 p.m., Room 6F, Lenalidomide in Combination with CHOP in Patients with Angioimmunoblastic T Cell Lymphoma (AITL): Final Analysis of Clinical and Molecular Data of a Phase 2 LYSA Study (Lemonnier)

Multiple Myeloma

New multiple myeloma data reinforces IMiD therapies as a foundation of myeloma research.

Abstract #112; Oral; Saturday, Dec 1, 10:15 a.m., Marriott Marquis San Diego Marina, Grand Ballroom 7, Clinical Significance and Transcriptional Profiling of Persistent Minimal Residual Disease (MRD) in Multiple Myeloma (MM) Patients With Standard-Risk (SR) and High-Risk (HR) Cytogenetics (Goicoechea)

Abstract #243; Oral; Saturday, Dec. 1, 4:30 p.m., Marriott Marquis San Diego Marina, Grand Ballroom 7, Deep immunoprofiling of the bone marrow microenvironment changes underlying the multistep progression of multiple myeloma (Young)

Abstract #121; Oral; Sunday, Dec 2, 8:30 a.m., Marriott Marquis San Diego Marina, Grand Ballroom 7, Efficacy and Feasibility of Dose/Schedule-Adjusted Rd-R vs. Continuous Rd in Elderly and Intermediate-Fit Newly Diagnosed Multiple Myeloma (NDMM) Patients: RV-MM-PI-0752 Phase III Randomized Study (Larocca)

Abstract #474; Oral; Sunday, Dec 2, 5:45 p.m., Marriott Marquis San Diego Marina, Grand Ballroom 7, Immunofixation (IF) in Urine is Really Necessary to Define Complete Remission in Multiple Myeloma (MM): A Subanalysis from the PETHEMA/GEM2012MENOS65 Phase III Clinical Trial (Ubieto)

Abstract #716; Oral; Monday, Dec. 3, 10:45 a.m., Room 25B, The Impact of Lenalidomide, Bortezomib, and Dexamethasone Treatment on Health-Related Quality of Life in Transplant-Eligible Patients with Newly-Diagnosed Multiple Myeloma: Results from the IFM/DFCI 2009 Trial (Roussel)

Abstract #1960; Poster; Saturday, Dec. 1, 6:00 p.m., Hall GH, Health-Related Quality of Life among Patients with Relapsed or Refractory Multiple Myeloma who Received Pomalidomide, Bortezomib, and Low-Dose Dexamethasone Versus Bortezomib and Low-Dose Dexamethasone – Results from the Phase 3 OPTIMISMM Study (Weisel)

Abstract #2012; Poster; Saturday, Dec. 1, 6:15 p.m., Hall GH, Immune Profiling of Relapsed or Refractory Multiple Myeloma Patients Treated With Pomalidomide and Low-Dose Dexamethasone in Combination With Daratumumab (Pierceall)

Abstract #2243; Poster; Saturday, Dec. 1, 6:15 p.m., Hall GH, Real-World Outcomes for Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma (NDMM) Treated With Lenalidomide, Bortezomib, and Dexamethasone (RVd) or Vd: An Enhanced Electronic Health Records (EHR) Database Analysis (Chari)

Abstract #3271; Poster; Sunday, Dec. 2, 6:00 p.m., Hall GH, Pomalidomide + Low-Dose Dexamethasone + Daratumumab in Relapsed and/or Refractory Multiple Myeloma after Lenalidomide-Based Treatment Failure (Siegel)

Abstract #3278; Poster; Sunday, Dec. 2, 6:00 p.m., Hall GH, Pomalidomide + Bortezomib + Low-Dose Dexamethasone vs Bortezomib + Low-Dose Dexamethasone as Second-Line Treatment in Patients with Lenalidomide-Pretreated Multiple Myeloma: A Subgroup Analysis of the Phase 3 OPTIMISMM Trial (Dimopoulos)

Abstract #3445; Poster; Sunday, Dec. 2, 6:00 p.m., Hall GH, The Impact of RVD or VCD Induction on Response 3 Months after First Line Autologous Transplant in Multiple Myeloma. A single-center Retrospective Analysis (Moksnes)

Abstract #3232; Poster; Sunday, Dec. 2, 6:00 p.m., Hall GH Treatment Choices and Outcomes for Patients with Multiple Myeloma (MM) After Relapse on Lenalidomide (LEN) Maintenance Therapy (mt): Results from the Connect MM Registry (Jagannath)

Abstract # 3245; Poster; Sunday, Dec. 2, 6:00 p.m., Hall GH, Integrated Analysis of Randomized Controlled Trials Evaluating Bortezomib + Lenalidomide + Dexamethasone or Bortezomib + Thalidomide + Dexamethasone Induction in Transplant-Eligible Newly Diagnosed Multiple Myeloma (Rosinol)

Abstract #4744; Poster; Monday, Dec. 3, 6:00 p.m., Hall GH, Relative Efficacy of Treatment Options in Newly Diagnosed Multiple Myeloma (NDMM): Results from a Systematic Literature Review (SLR) and Network Meta-Analysis (NMA) (Ramasamy)

Abstract #4737; Poster; Monday, Dec. 3, 6:00 p.m., Hall GH, Survival Analysis from the CALGB Study of Lenalidomide Maintenance Therapy in Newly Diagnosed Multiple Myeloma Post-Autologous Stem Cell Transplantation Adjusted for Crossover (McCarthy)

The safety and efficacy of investigational agents and/or investigational uses of approved marketed products have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

A complete listing of abstracts can be found on the ASH (Free ASH Whitepaper) Web site at View Source

*All times Pacific Standard Time

ABOUT REVLIMID

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

REVLIMID is indicated as maintenance therapy in patients with MM following autologous hematopoietic stem cell transplantation (auto-HSCT)

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

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.

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 risk to the fetus

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

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity: See Boxed WARNINGS

Females of Reproductive Potential: See Boxed WARNINGS
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 4 weeks 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 4 weeks 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: See Boxed WARNINGS: Prescribers and pharmacies must be certified with the REVLIMID REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive REVLIMID. Patients must sign a Patient-Physician Agreement Form and comply with REMS requirements; female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements and males must comply with contraception requirements

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 or REVLIMID as maintenance therapy 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. MDS: 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 dose reduction. Please see the Black Box WARNINGS for further information. 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

Venous and Arterial Thromboembolism: See Boxed WARNINGS: Venous thromboembolic events (DVT and PE) and arterial thromboses (MI and CVA) are increased in patients treated with REVLIMID. 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). Thromboprophylaxis is recommended and the regimen should be based on patient’s underlying risks. ESAs and estrogens may further increase the risk of thrombosis and their use should be based on a benefit-risk decision

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. Serious adverse cardiovascular reactions, including atrial fibrillation, myocardial infarction, and cardiac failure, occurred more frequently in the REVLIMID arm. REVLIMID is not indicated and not recommended for use in CLL outside of controlled clinical trials

Second Primary Malignancies (SPM): In clinical trials in patients with MM receiving REVLIMID, an increase of hematologic plus solid tumor SPM, notably AML and MDS, have been observed. Monitor patients for the development of SPM. Take into account both the potential benefit of REVLIMID and risk of SPM when considering treatment

Increased Mortality with Pembrolizumab: In clinical trials in patients with multiple myeloma, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials

Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with REVLIMID/dex. 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

Severe Cutaneous Reactions Including Hypersensitivity Reactions: Angioedema and severe cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. DRESS may present with a cutaneous reaction (such as rash, or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. 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, TEN, or DRESS is suspected and should not be resumed following discontinuation for these reactions

Tumor Lysis Syndrome (TLS): Fatal instances of 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 (TFR): TFR has occurred during investigational use of lenalidomide for CLL and lymphoma. 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 REVLIMID until TFR resolves to ≤Grade 1. REVLIMID may be continued in patients with Grade 1 and 2 TFR without interruption or modification, at the physician’s discretion

Impaired Stem Cell Mobilization: A decrease in the number of CD34+ cells collected after treatment (>4 cycles) with REVLIMID has been reported. Consider early referral to transplant center to optimize timing of the stem cell collection

Thyroid Disorders: Both hypothyroidism and hyperthyroidism have been reported. Measure thyroid function before start of REVLIMID treatment and during therapy

Early Mortality in Patients with MCL: In another MCL study, there was an increase in early deaths (within 20 weeks), 12.9% in the REVLIMID arm versus 7.1% in the control arm. Risk factors for early deaths include high tumor burden, MIPI score at diagnosis, and high WBC at baseline (≥10 x 109/L)

ADVERSE REACTIONS

Multiple Myeloma

In newly diagnosed: The most frequently reported Grade 3 or 4 reactions included neutropenia, anemia, thrombocytopenia, pneumonia, asthenia, fatigue, back pain, hypokalemia, rash, cataract, lymphopenia, dyspnea, DVT, hyperglycemia, and leukopenia. The highest frequency of infections occurred in Arm Rd Continuous (75%) compared to Arm MPT (56%). There were more Grade 3 and 4 and serious adverse reactions of infection in Arm Rd Continuous than either Arm MPT or Rd18
The most common adverse reactions reported in ≥20% (Arm Rd Continuous): diarrhea (46%), anemia (44%), neutropenia (35%), fatigue (33%), back pain (32%), asthenia (28%), insomnia (28%), rash (26%), decreased appetite (23%), cough (23%), dyspnea (22%), pyrexia (21%), abdominal pain (21%), muscle spasms (20%), and thrombocytopenia (20%)
Maintenance Therapy Post Auto-HSCT: The most frequently reported Grade 3 or 4 reactions in ≥20% (REVLIMID arm) included neutropenia, thrombocytopenia, and leukopenia. The serious adverse reactions of lung infection and neutropenia (more than 4.5%) occurred in the REVLIMID arm
The most frequently reported adverse reactions in ≥20% (REVLIMID arm) across both maintenance studies (Study 1, Study 2) were neutropenia (79%, 61%), thrombocytopenia (72%, 24%), leukopenia (23%, 32%), anemia (21%, 9%), upper respiratory tract infection (27%, 11%), bronchitis (5%, 47%), nasopharyngitis (2%, 35%), cough (10%, 27%), gastroenteritis (0%, 23%), diarrhea (55%, 39%), rash (32%, 8%), fatigue (23%, 11%), asthenia (0%, 30%), muscle spasm (0%, 33%), and pyrexia (8%, 21%)
After at least one prior therapy: The most common adverse reactions reported in ≥20% (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%), and weight decreased (20% vs 15%)
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%)
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 is recommended due to increased Cmax and AUC with concomitant REVLIMID therapy. Patients taking concomitant therapies such as erythropoietin stimulating agents or estrogen containing therapies may have an increased risk of thrombosis. It is not known whether there is an interaction between dex and warfarin. Close monitoring of PT and INR is recommended in patients with MM taking concomitant warfarin

USE IN SPECIFIC POPULATIONS

PREGNANCY: See Boxed WARNINGS: If pregnancy does occur during treatment, immediately discontinue the drug and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. There is a REVLIMID pregnancy exposure registry that monitors pregnancy outcomes in females exposed to REVLIMID during pregnancy as well as female partners of male patients who are exposed to REVLIMID. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to REVLIMID to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423-5436
LACTATION: There is no information regarding the presence of lenalidomide in human milk, the effects of REVLIMID on the breastfed infant, or the effects of REVLIMID on milk production. Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants from REVLIMID, advise female patients not to breastfeed during treatment with REVLIMID
PEDIATRIC USE: Safety and effectiveness have not been established in pediatric patients
RENAL IMPAIRMENT: Adjust the starting dose of REVLIMID based on the creatinine clearance value and in patients on dialysis
Please see full Prescribing Information , including Boxed WARNINGS.

About POMALYST/IMNOVID

POMALYST (pomalidomide) is a thalidomide analogue indicated, in combination with dexamethasone, for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity

POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting POMALYST treatment.
Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping POMALYST treatment.
POMALYST is only available through a restricted distribution program called POMALYST REMS .

Venous and Arterial Thromboembolism

Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with POMALYST. Prophylactic antithrombotic measures were employed in clinical trials. Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient’s underlying risk factors.

CONTRAINDICATIONS

Pregnancy : POMALYST can cause fetal harm and is contraindicated in females who are pregnant. If POMALYST is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus.
WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity & Females of Reproductive Potential: See Boxed WARNINGS
Males: Pomalidomide 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 POMALYST and for up to 4 weeks after discontinuing POMALYST, even if they have undergone a successful vasectomy. Males must not donate sperm.
Blood Donation: Patients must not donate blood during treatment with POMALYST and for 4 weeks following discontinuation of POMALYST therapy because the blood might be given to a pregnant female patient whose fetus must not be exposed to POMALYST.
POMALYST REMS Program: See Boxed WARNINGS
Prescribers and pharmacies must be certified with the POMALYST REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive POMALYST. Patients must sign a Patient-Physician Agreement Form and comply with REMS requirements; female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements and males must comply with contraception requirements.
Further information about the POMALYST REMS program is available at www.CelgeneRiskManagement.com or by telephone at 1-888-423-5436.
Venous and Arterial Thromboembolism: See Boxed WARNINGS. 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). Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient’s underlying risk factors.
Increased Mortality with Pembrolizumab : In clinical trials in patients with multiple myeloma, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.
Hematologic Toxicity : Neutropenia (46%) was the most frequently reported Grade 3/4 adverse reaction in patients taking POMALYST in clinical trials, followed by anemia and thrombocytopenia. Monitor complete blood counts weekly for the first 8 weeks and monthly thereafter. Patients may require dose interruption and/or modification.
Hepatotoxicity : Hepatic failure, including fatal cases, has occurred in patients treated with POMALYST. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with POMALYST. Monitor liver function tests monthly. Stop POMALYST upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered.
Severe Cutaneous Reactions Including Hypersensitivity Reactions : Angioedema and severe cutaneous reactions including Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. Discontinue POMALYST for angioedema, skin exfoliation, bullae, or any other severe cutaneous reactions such as SJS, TEN or DRESS, and do not resume therapy.
Dizziness and Confusional State : In patients taking POMALYST in clinical trials, 14% experienced dizziness (1% Grade 3 or 4) and 7% a confusional state (3% Grade 3 or 4). Instruct patients to avoid situations where dizziness or confusional state may be a problem and not to take other medications that may cause dizziness or confusional state without adequate medical advice.
Neuropathy : In patients taking POMALYST in clinical trials, 18% experienced neuropathy (2% Grade 3 in one trial) and 12% peripheral neuropathy.
Second Primary Malignancies : Cases of acute myelogenous leukemia have been reported in patients receiving POMALYST as an investigational therapy outside of multiple myeloma.
Tumor Lysis Syndrome (TLS) : TLS may occur in patients treated with POMALYST. Patients at risk are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken.
ADVERSE REACTIONS

The most common adverse reactions for POMALYST (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain, and pyrexia.

In the phase III trial, nearly all patients treated with POMALYST + low-dose dex experienced at least one adverse reaction (99%). Adverse reactions (≥15% in the POMALYST + low-dose dex arm and ≥2% higher than control) included neutropenia (51.3%), fatigue and asthenia (46.7%), upper respiratory tract infection (31%), thrombocytopenia (29.7%), pyrexia (26.7%), dyspnea (25.3%), diarrhea (22%), constipation (21.7%), back pain (19.7%), cough (20%), pneumonia (19.3%), bone pain (18%), edema peripheral (17.3%), peripheral neuropathy (17.3%), muscle spasms (15.3%), and nausea (15%). Grade 3 or 4 adverse reactions (≥15% in the POMALYST + low-dose dex arm and ≥1% higher than control) included neutropenia (48.3%), thrombocytopenia (22%), and pneumonia (15.7%).

DRUG INTERACTIONS

Avoid concomitant use of POMALYST with strong inhibitors of CYP1A2. Consider alternative treatments. If a strong CYP1A2 inhibitor must be used, reduce POMALYST dose by 50%.

USE IN SPECIFIC POPULATIONS

Pregnancy: See Boxed WARNINGS. If pregnancy does occur during treatment, immediately discontinue the drug and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. There is a POMALYST pregnancy exposure registry that monitors pregnancy outcomes in females exposed to POMALYST during pregnancy as well as female partners of male patients who are exposed to POMALYST. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to POMALYST to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423-5436.
Lactation : There is no information regarding the presence of pomalidomide in human milk, the effects of POMALYST on the breastfed child, or the effects of POMALYST on milk production. Pomalidomide was excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for adverse reactions in a breastfed child from POMALYST, advise women not to breastfeed during treatment with POMALYST.
Pediatric Use : Safety and effectiveness have not been established in pediatric patients.
Geriatric Use : No dosage adjustment is required for POMALYST based on age. Patients >65 years of age were more likely than patients ≤65 years of age to experience pneumonia.
Renal Impairment : Reduce POMALYST dose by 25% in patients with severe renal impairment requiring dialysis. Take dose of POMALYST following hemodialysis on hemodialysis days.
Hepatic Impairment : Reduce POMALYST dose by 25% in patients with mild to moderate hepatic impairment and 50% in patients with severe hepatic impairment.
Smoking Tobacco : Advise patients that smoking may reduce the efficacy of POMALYST. Cigarette smoking reduces the AUC of pomalidomide by 32% by CYP1A2 induction.
Please see full Prescribing Information , including Boxed WARNINGS.

About IDHIFA

IDHIFA (enasidenib) is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-2 mutation as detected by an FDA-approved test.

Important Safety Information

WARNING: DIFFERENTIATION SYNDROME

Patients treated with IDHIFA have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, lymphadenopathy, bone pain, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome: See Boxed WARNING. In the clinical trial, 14% of patients treated with IDHIFA experienced differentiation syndrome, which may be life-threatening or fatal if not treated. Differentiation syndrome has been observed with and without concomitant hyperleukocytosis, as early as 10 days and at up to 5 months after IDHIFA initiation. Symptoms in patients treated with IDHIFA included acute respiratory distress represented by dyspnea and/or hypoxia and need for supplemental oxygen; pulmonary infiltrates and pleural effusion; renal impairment; fever; lymphadenopathy; bone pain; peripheral edema with rapid weight gain; and pericardial effusion. Hepatic, renal, and multi-organ dysfunction have also been observed. If differentiation syndrome is suspected, initiate systemic corticosteroids and hemodynamic monitoring until improvement. Taper corticosteroids only after resolution of symptoms. Differentiation syndrome symptoms may recur with premature discontinuation of corticosteroids. If severe pulmonary symptoms requiring intubation or ventilator support and/or renal dysfunction persist for more than 48 hours after initiation of corticosteroids, interrupt IDHIFA until signs and symptoms are no longer severe. Hospitalization for close observation and monitoring of patients with pulmonary and/or renal manifestation is recommended.

Embryo-Fetal Toxicity:Based on animal embryo-fetal toxicity studies, IDHIFA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with IDHIFA and for at least 1 month after the last dose. Pregnant women, patients becoming pregnant while receiving IDHIFA, or male patients with pregnant female partners should be apprised of the potential risk to the fetus.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) included total bilirubin increased (81%), calcium decreased (74%), nausea (50%), diarrhea (43%), potassium decreased (41%), vomiting (34%), decreased appetite (34%), and phosphorus decreased (27%)
The most frequently reported ≥Grade 3 adverse reactions (≥5%) included total bilirubin increased (15%), potassium decreased (15%), phosphorus decreased (8%), calcium decreased (8%), diarrhea (8%), differentiation syndrome (7%), non-infectious leukocytosis (6%), tumor lysis syndrome (6%), and nausea (5%)
Serious adverse reactions were reported in 77.1% of patients. The most frequent serious adverse reactions (≥2%) were leukocytosis (10%), diarrhea (6%), nausea (5%), vomiting (3%), decreased appetite (3%), tumor lysis syndrome (5%), and differentiation syndrome (8%). Differentiation syndrome events characterized as serious included pyrexia, renal failure acute, hypoxia, respiratory failure, and multi-organ failure
LACTATION

Many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants, advise women not to breastfeed during treatment with IDHIFA and for at least 1 month after the last dose.

On November 1, 2018 Incyte (Nasdaq:INCY) reported that multiple abstracts, including data from its clinical development programs for ruxolitinib (Jakafi), pemigatinib and INCB50465 will be presented at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting 2018 in San Diego, California, from December 1-4, 2018 (Press release, Incyte, NOV 1, 2018, View Source [SID1234530536]).

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Key data presented at ASH (Free ASH Whitepaper) 2018 will include results from the pivotal REACH1 trial evaluating ruxolitinib in combination with corticosteroids for the treatment of patients with acute graft-versus-host disease (GVHD) who have had an inadequate response to corticosteroids, which have been accepted for oral presentation. Additionally, new data from the Phase 2 study evaluating INCB50465 in combination with ruxolitinib in patients with myelofibrosis (MF) and initial data from the Phase 2 fight-203 study evaluating pemigatinib in patients with myeloproliferative neoplasms (MPNs) with activating FGFR1 translocations have been accepted for oral presentation.

"We are looking forward to highlighting our later-stage, targeted therapy portfolio at this year’s ASH (Free ASH Whitepaper) Annual Meeting," said Steven Stein, M.D., Chief Medical Officer, Incyte. "Specifically, we are pleased to present results from our REACH1 study, which formed the basis of our supplemental new drug application for ruxolitinib as a treatment for acute GVHD that is currently under Priority Review by the FDA, and new data from our INCB50465 and pemigatinib clinical development programs, which further underscore our leadership in MPNs."

Key abstract presentations include:

Ruxolitinib (Jakafi)

Oral Presentations

Safety and Efficacy of Combined Ruxolitinib and Thalidomide in Patients with Myelofibrosis: Initial Results of a Phase 2 Study (Abstract #354)

Sunday, December 2, 2018, 9:30-11:00 a.m., Manchester Grand Hyatt, Seaport Ballroom F, Oral Session 634, Myeloproliferative Syndromes: Clinical: Addressing Areas of Unmet Need in Prognostic Assessments and Therapy for MPNs
Results from REACH1, a Single-arm Phase 2 Study of Ruxolitinib in Combination with Corticosteroids for the Treatment of Steroid-Refractory Acute Graft-vs-Host Disease (Abstract #601)

Monday, December 3, 2018, 7:00-8:30 a.m., Manchester Grand Hyatt, Grand Hall A, Oral Session 722, Clinical Allogeneic Transplantation: Acute and Chronic GVHD
A Phase 2 Study of Ruxolitinib with Chemotherapy in Children with Philadelphia Chromosome-like Acute Lymphoblastic Leukemia (INCB18424-269/AALL1521): Dose-Finding Results from the Part 1 Safety Phase (Abstract #555)

Monday, December 3, 2018, 7:00-8:30 a.m., San Diego Convention Center, Ballroom 20A, Oral Session 614, Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Targeted Therapy in ALL: Immunotherapy and Beyond
RUXOPEG, a Multi-Center Bayesian Phase ½ Adaptive Randomized Trial of the Combination of Ruxolitinib and Pegylated Interferon Alpha 2a in Patients with Myeloproliferative Neoplasms-Associated Myelofibrosis*(Abstract #581)

Monday, December 3, 2018, 7:00-8:30 a.m., Manchester Grand Hyatt, Grand Hall D, Oral Session 634, Myeloproliferative Syndromes: Clinical: Interferon Therapy and Mutational Analysis in the MPNs
Poster Sessions

Updated Results from An Open-Label, Multicenter, Expanded Treatment Protocol (ETP) Phase (Ph) 3b Study Of Ruxolitinib (Rux) In Patients (Pts) With Polycythemia Vera (PV) Who Are Hydroxyurea (HU) Resistant Or Intolerant And For Whom No Alternative Treatments Are Available (Abstract #1774)

Saturday, December 1, 2018, 6:15-8:15 p.m., San Diego Convention Center, Hall GH, Poster Session 634, Myeloproliferative Syndromes: Clinical: Poster I
Characteristics Associated with Hydroxyurea Treatment Change in Patients with Polycythemia Vera: An Analysis from the REVEAL Study (Abstract #1770)

Saturday, December 1, 2018, 6:15-8:15 p.m., San Diego Convention Center, Hall GH, Poster Session 634, Myeloproliferative Syndromes: Clinical: Poster I
Real-World Risk Assessment and Treatment of Patients with Myelofibrosis at Community Oncology Practices in the United States(Abstract #1765)

Saturday, December 1, 2018, 6:15-8:15 p.m., San Diego Convention Center, Hall GH, Poster Session 634, Myeloproliferative Syndromes: Clinical: Poster I
Impact of Myeloproliferative Neoplasms on Patients’ Employment and Income: Findings from the Living with MPN Survey(Abstract #2250)

Saturday, December 1, 2018, 6:15-8:15 p.m., San Diego Convention Center, Hall GH, Poster Session 902, Health Services Research – Malignant Diseases: Poster I
Elevated White Blood Cell levels and Thrombotic Events in Patients with Polycythemia Vera: A Real-World Analysis of Veterans Health Administration Data (Abstract #1758)

Saturday, December 1, 2018, 6:15-8:15 p.m., San Diego Convention Center, Hall GH, Poster Session 634, Myeloproliferative Syndromes: Clinical: Poster I
Correlation between MPN-SAF TSS and EORTC QLQ-C30 Scores in Patients with PV: Data from the REVEAL Study (Abstract #2259)

Saturday, December 1, 2018, 6:15-8:15 p.m., San Diego Convention Center, Hall GH, Poster Session 902, Health Services Research – Malignant Diseases: Poster I
Long-term Efficacy and Safety (5 Years) in RESPONSE, a Phase 3 Study Comparing Ruxolitinib (rux) With Best Available Therapy (BAT) in Hydroxyurea (HU)-resistant/intolerant Patients (pts) With Polycythemia Vera (PV)

Saturday, December 1, 2018, 6:15-8:15 p.m., San Diego Convention Center, Hall GH, Poster Session 634, Myeloproliferative Syndromes: Clinical: Poster I
Ruxolitinib for the Treatment of Inadequately Controlled Polycythemia Vera Without Splenomegaly: 156-Week Follow-Up From the Phase 3 RESPONSE-2 Study (Abstract #1754)

Saturday, December 1, 2018, 6:15-8:15 p.m., San Diego Convention Center, Hall GH, Poster Session 634, Myeloproliferative Syndromes: Clinical: Poster I
Disease and Clinical Characteristics of Patients with Essential Thrombocythemia Enrolled in the MOST Study (Abstract #4306)

Monday, December 3, 2018, 6:00-8:00 p.m., San Diego Convention Center, Hall GH, Poster Session 634, Myeloproliferative Syndromes: Clinical: Poster III
Disease Characteristics of Minority Patient Populations with Polycythemia Vera: An Analysis from the REVEAL Study (Abstract #4735)

Monday, December 3, 2018, 6:00-8:00 p.m., San Diego Convention Center, Hall GH, Poster Session 902, Health Services Research – Malignant Diseases: Poster III
Real-World Management of Myelofibrosis with Ruxolitinib: Initial Analysis of an Italian Observational Study (ROMEI) (Abstract #4312)

Monday, December 3, 2018, 6:00-8:00 p.m., San Diego Convention Center, Hall GH, Poster Session 634, Myeloproliferative Syndromes: Clinical: Poster III
Impact of Myeloproliferative Neoplasms (MPNs) on Health-Related Quality of Life (HRQOL) and Medical Resource Utilization: Results from the MERGE Registry (Abstract #4311)

Monday, December 3, 2018, 6:00-8:00 p.m., San Diego Convention Center, Hall GH, Poster Session 634: Myeloproliferative Syndromes: Clinical: Poster III
INCB50465 (PI3Kδ)

Oral Presentation

A Phase 2 Study of the Safety and Efficacy of INCB050465, a Selective PI3Kδ Inhibitor, in Combination with Ruxolitinib in Patients with Myelofibrosis (Abstract #353)

Sunday, December 2, 2018, 9:30-11:00 a.m., Manchester Grand Hyatt, Seaport Ballroom F, Oral Session 634, Myeloproliferative Syndromes: Clinical: Addressing Areas of Unmet Need in Prognostic Assessments and Therapy for MPNs
Poster Session

Cell-of-Origin Subtype Prediction of Diffuse Large B-cell Lymphoma Using Gene Expression and Proteomic Data (Abstract #1712)

Saturday, December 1, 2018, 6:15-8:15 p.m., San Diego Convention Center, Hall GH, Poster Session 627, Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Retrospective/Observational Studies: Poster I
Pemigatinib (INCB054828)

Oral Presentation

Interim Results from fight-203, a Phase 2, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Pemigatinib (INCB054828) in Patients with Myeloid/Lymphoid Neoplasms with Rearrangement of Fibroblast Growth Factor Receptor 1 (FGFR1) (Abstract #690)

Monday, December 3, 2018, 10:30-12:00 p.m., Manchester Grand Hyatt, Grand Hall A, Oral Session 634, Myeloproliferative Syndromes: Clinical: Emerging Therapies and Prognostic Scoring in Myelofibrosis and Other MPNs
Itacitinib

Plasma Biomarker Association with Response in Acute GVHD Subjects Treated With the Combination of Itacitinib and Corticosteroids in a Phase 1 Clinical Trial (Abstract #4559)

Monday, December 3, 2018, 6:00-8:00 p.m., San Diego Convention Center, Hall GH, Poster Session 722, Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster III
Ponatinib

Efficacy and Safety of Ponatinib in CML and Ph+ ALL Patients in Real World Clinical Practice – Data from a Belgian Registry (Abstract #1744)

Saturday, December 1, 2018, 6:15-8:15 p.m., San Diego Convention Center, Hall GH, Poster Session 632, Chronic Myeloid Leukemia: Therapy: Poster I
Preclinical

The Persistent Survival of MPN Cells to JAK2 Inhibition is Dependent on SHP2 Activity, Which May Provide a Therapeutic Target to Enhance Current Anti-MPN Therapies (Abstract #3064)

Sunday, December 2, 2018, 6:00-8:00 p.m., San Diego Convention Center, Hall GH, Poster Session 635, Myeloproliferative Syndromes: Basic Science: Poster II
Itacitinib, a JAK1 Selective Inhibitor Preserves Graft-versus-Leukemia (GVL), Enhances Survival and is Highly Efficacious in a MHC-mismatched Mouse Model of Acute GvHD (Abstract #4522)

Monday, December 3, 2018, 6:00-8:00 p.m., San Diego Convention Center, Hall GH, Poster Session 701, Experimental Transplantation: Basic Biology, Pre-Clinical Models Poster III
Ruxolitinib, a JAK1/JAK2 Selective Inhibitor is Highly Efficacious in Corticosteroid Untreated and Refractory MHC-mismatched Mouse Model of Acute GvHD (Abstract 4523)

Monday, December 3, 2018, 6:00-8:00 p.m., San Diego Convention Center, Hall GH, Poster Session 701, Experimental Transplantation: Basic Biology, Pre-Clinical Models: Poster III
Full session details and data presentation listings for ASH (Free ASH Whitepaper) 2018 can be found at: View Source

About Jakafi(ruxolitinib)

Jakafi is a first-in-class JAK1/JAK2 inhibitor approved by the U.S. Food and Drug Administration for treatment of people with polycythemia vera (PV) who have had an inadequate response to or are intolerant of hydroxyurea.

Jakafi is also indicated for treatment of people with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF, and post–essential thrombocythemia MF.

Jakafi is marketed by Incyte in the United States and by Novartis as Jakavi (ruxolitinib) outside the United States. Jakafi is a registered trademark of Incyte Corporation. Jakavi is a registered trademark of Novartis AG in countries outside the United States. Ruxolitinib is also being evaluated in patients with acute and chronic GVHD who have an inadequate response to corticosteroids in the REACH2 and REACH3 clinical studies, respectively. It is expected that these two pivotal studies will complete in 2019, and could support additional regulatory submissions, in the U.S. by Incyte and ex-U.S. by Novartis, in 2020.

Important Safety Information

Jakafi can cause serious side effects, including:

Low blood counts: Jakafi (ruxolitinib) may cause your platelet, red blood cell, or white blood cell counts to be lowered. If you develop bleeding, stop taking Jakafi and call your healthcare provider. Your healthcare provider will perform blood tests to check your blood counts before you start Jakafi and regularly during your treatment. Your healthcare provider may change your dose of Jakafi or stop your treatment based on the results of your blood tests. Tell your healthcare provider right away if you develop or have worsening symptoms such as unusual bleeding, bruising, tiredness, shortness of breath, or a fever.

Infection: You may be at risk for developing a serious infection during treatment with Jakafi. Tell your healthcare provider if you develop any of the following symptoms of infection: chills, nausea, vomiting, aches, weakness, fever, painful skin rash or blisters.

Skin cancers: Some people who take Jakafi have developed certain types of non-melanoma skin cancers. Tell your healthcare provider if you develop any new or changing skin lesions.

Increases in Cholesterol: You may have changes in your blood cholesterol levels. Your healthcare provider will do blood tests to check your cholesterol levels during your treatment with Jakafi.

The most common side effects of Jakafi include: low platelet count, low red blood cell counts, bruising, dizziness, headache.

These are not all the possible side effects of Jakafi. Ask your pharmacist or healthcare provider for more information. Tell your healthcare provider about any side effect that bothers you or that does not go away.

Before taking Jakafi, tell your healthcare provider about: all the medications, vitamins, and herbal supplements you are taking and all your medical conditions, including if you have an infection, have or had tuberculosis (TB), or have been in close contact with someone who has TB, have or had hepatitis B, have or had liver or kidney problems, are on dialysis, had skin cancer or have any other medical condition. Take Jakafi exactly as your healthcare provider tells you. Do not change or stop taking Jakafi without first talking to your healthcare provider. Do not drink grapefruit juice while on Jakafi.

Women should not take Jakafi while pregnant or planning to become pregnant, or if breast-feeding.

Full Prescribing Information, which includes a more complete discussion of the risks associated with Jakafi, is available at www.jakafi.com.

On November 1, 2018 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported business highlights and financial results for the third quarter ended September 30, 2018 (Press release, Agios Pharmaceuticals, NOV 1, 2018, View Source [SID1234530489]).

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"On the heels of the third quarter U.S. approval of TIBSOVO, our first wholly owned precision medicine, we remain focused on executing on our remaining 2018 milestones and continuing to create value from our portfolio," said David Schenkein, M.D., chief executive officer at Agios. "Based on regulatory discussions, we are accelerating our frontline strategy in IDH1m AML with the planned submission of an sNDA expanding TIBSOVO’s label to newly diagnosed AML patients not eligible for standard treatment and a shorter enrollment timeline for the Phase 3 AGILE trial. In addition, we continue to activate new sites globally for our pivotal PK deficiency program and accrue patients in the dose-escalation portion of the Phase 1 study in MTAP-deleted tumors. We believe these programs coupled with our robust preclinical pipeline, support our next phase of growth toward becoming a fully integrated, sustainable biopharmaceutical company."

THIRD QUARTER & RECENT 2018 HIGHLIGHTS

Launched TIBSOVO (ivosidenib) for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by a test approved by the U.S. Food and Drug Administration (FDA).
Awarded the U.S. Prix Galien Award for Best Pharmaceutical Product of 2018 for IDHIFA (enasidenib), an isocitrate dehydrogenase-2 (IDH2) inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH2 mutation as detected by a test approved by the FDA. Each year, the Prix Galien USA Committee recognizes outstanding achievements in improving the human condition through the development of innovative therapies.
Reached agreement with the FDA to submit a supplemental new drug application (sNDA) for single agent TIBSOVO in newly diagnosed AML patients with an IDH1 mutation who are not eligible for standard treatment.
Reached agreement with the FDA that event free survival (EFS) is an acceptable primary endpoint for the Phase 3 AGILE trial of ivosidenib combination with azacitidine in newly diagnosed AML patients with an IDH1 mutation who are ineligible for intensive chemotherapy. Full enrollment for AGILE is now expected to complete in 2020 vs. previous guidance of 2021.
Received global rights to AG-881, a brain-penetrant, pan-IDH inhibitor that was previously part of a joint worldwide collaboration with Celgene.
Submitted an investigational new drug (IND) application for AG-636, an inhibitor of the metabolic enzyme dihydroorotate dehydrogenase (DHODH) for the treatment of hematologic malignancies.
Announced that effective February 1, 2019, CEO David Schenkein, M.D., will transition to the role of executive chairman of the board of directors and Jacqualyn ("Jackie") Fouse, Ph.D., will succeed Dr. Schenkein as Agios’ next chief executive officer.
KEY UPCOMING MILESTONES

The company expects to achieve the following near-term milestones:

Cancer:

Submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for TIBSOVO for the treatment of adult patients with R/R AML with an IDH1 mutation by year end 2018.
Support, in conjunction with Celgene, the initiation of HOVON 150, an intergroup sponsored, global, registration-enabling Phase 3 trial combining ivosidenib or enasidenib with standard induction and consolidation chemotherapy followed by a maintenance therapy period in frontline AML patients with an IDH1 or IDH2 mutation, respectively, by year end 2018.
Submit an sNDA to the FDA for TIBSOVO for the treatment of patients with newly diagnosed AML with an IDH1 mutation who are not eligible for standard therapy by the end of January 2019.
Rare Genetic Diseases:

Initiate a Phase 2 proof-of-concept trial of mitapivat in thalassemia by year end 2018.
FOURTH QUARTER CLINICAL DATA PRESENTATIONS

Updated data from Phase 1 trial of AG-881 in solid tumors, including glioma, has been accepted as an oral presentation at the 2018 Society for Neuro-Oncology (SNO) Annual Meeting on November 15-18 in New Orleans.
Updated data from the ongoing Phase 1 trial of single agent ivosidenib in IDH1m hematologic malignancies in a subset of patients with newly diagnosed AML not eligible for standard therapy has been accepted as an oral presentation at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition on December 1-4 in San Diego.
Updated data from the ongoing Phase 1 combination trial of ivosidenib or enasidenib with standard-of-care intensive chemotherapy in patients with newly diagnosed AML with an IDH2 or IDH1 mutation also been accepted as an oral presentation at ASH (Free ASH Whitepaper).
Updated data in myelodysplastic syndrome (MDS) from the ongoing Phase 1 study of single agent ivosidenib in IDH1m hematologic malignancies has been accepted as a poster presentation at ASH (Free ASH Whitepaper).
THIRD QUARTER 2018 FINANCIAL RESULTS

Revenue for the quarter ended September 30, 2018 was $15.2 million, which includes $4.5 million of net product revenue from U.S. sales of TIBSOVO, $8.7 million of collaboration revenue and $2.0 million of royalty revenue from net global sales of IDHIFA under our collaboration agreements with Celgene. Revenue for the quarter ended September 30, 2017 was $11.4 million and consisted of $10.6 million of collaboration revenue and $0.7 million of royalty revenue under our agreements with Celgene. The year-over-year increase in total revenue for the third quarter was primarily driven by U.S. sales of TIBSOVO and royalty revenue from U.S. sales of IDHIFA, offset by a decrease in collaboration revenue recognized during the quarter.

Cost of sales for the quarter ended September 30, 2018 were $0.7 million and relate to manufacturing costs associated with TIBSOVO sales.

Research and development (R&D) expenses were $82.6 million, including $13.4 million of stock-based compensation expense, for the quarter ended September 30, 2018, compared to $72.9 million, including $7.6 million in stock-based compensation expense, for the comparable period in 2017. The increase in R&D expense was primarily attributable to start-up costs for the mitapivat (AG-348) pivotal program in PK deficiency and IND enabling activities for AG-636, our DHODH inhibitor. R&D expense also increased as a result of ongoing research efforts across our discovery platform programs.

Sales, general and administrative (SG&A) expenses were $31.1 million, including $10.8 million of stock-based compensation expense, for the quarter ended September 30, 2018, compared to $17.5 million, including $4.6 million of stock-based compensation expense, for the quarter ended September 30, 2017. The increase in SG&A expense was primarily attributable to the growth in our U.S. commercial organization to support the launch of TIBSOVO and personnel costs related to increased headcount.

Net loss for the quarter ended September 30, 2018 was $94.7 million, compared to a net loss of $77.1 million for the quarter ended September 30, 2017.

Cash, cash equivalents and marketable securities as of September 30, 2018 were $878.4 million, compared to $567.8 million as of December 31, 2017. The increase in cash was driven by the net proceeds of $516.2 million from the January follow-on offering, $14.8 million of cost reimbursements and royalty payments under our collaboration agreements with Celgene, $12.0 million under our collaboration agreement with CStone and $29.2 million received from employee stock transactions. This was offset by expenditures to fund operations of $263.0 million during the nine months ended September 30, 2018.

The company expects that its cash, cash equivalents and marketable securities as of September 30, 2018, together with anticipated product and royalty revenue, anticipated interest income, and anticipated expense reimbursements under our collaboration and license agreements, but excluding any additional program-specific milestone payments, will enable the company to fund its anticipated operating expenses and capital expenditure requirements through at least the end of 2020.

CONFERENCE CALL INFORMATION

Agios will host a conference call and live webcast with slides today at 8:00 a.m. ET to discuss third quarter 2018 financial results and recent business activities. To participate in the conference call, please dial 1-877-377-7098 (domestic) or 1-631-291-4547 (international) and referring to conference ID 5285068. The live webcast can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.