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US FDA ACCEPTS REGULATORY SUBMISSION FOR ACALABRUTINIB AND GRANTS PRIORITY REVIEW

On August 2, 2017 AstraZeneca and its haematology research and development centre of excellence, Acerta Pharma, reported that the US Food and Drug Administration (FDA) has accepted and granted priority review for the New Drug Application (NDA) for acalabrutinib, a highly-selective, potent, Bruton tyrosine kinase (BTK) inhibitor (Press release, AstraZeneca, AUG 2, 2017, View Source [SID1234519987]).

The NDA is based on results from the Phase II ACE-LY-004 clinical trial, which evaluated the safety and efficacy of acalabrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL) who have received at least one prior therapy. This follows the FDA’s recent Breakthrough Therapy Designation for acalabrutinib.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, said: "FDA’s acceptance of the acalabrutinib application and Priority Review illustrates the impact it could have on patients with relapsed or refractory mantle cell lymphoma as we work to bring this potential medicine to those in need as quickly as possible."

Priority Review is granted to applications for medicines that, if approved, would offer a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions.[1] The Prescription Drug User Fee Act (PDUFA) date is during the first quarter of 2018.

Flavia Borellini, PhD, Acerta Pharma Chief Executive Officer, said: "We believe acalabrutinib has the potential to be a very important treatment option for patients with this life-threatening blood cancer. The FDA’s NDA acceptance exemplifies our progress in the acalabrutinib development programme and continues our momentum as we seek to transform care for people with haematologic malignancies."

Results from the ACE-LY-004 clinical trial will be submitted for presentation at a forthcoming medical meeting. The acalabrutinib development programme includes both monotherapy and combination therapy strategies in a broad range of blood cancers and solid tumours. The programme includes the Phase III ACE-LY-308 clinical trial evaluating acalabrutinib as a 1st-line treatment for patients with MCL.[2]

About mantle cell lymphoma (MCL)
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) with poor prognosis.[3],[4],[5],[6] MCL accounts for approximately 3% to 6% of new NHL cases in Western countries each year, with an annual incidence of 0.5 per 100,000 persons and an estimated prevalence of 3.5/100,000.5,[7] The median age at diagnosis is 68 years, with a 3:1 male predominance.5

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About acalabrutinib
Acalabrutinib is a highly-selective, potent, covalent inhibitor of Bruton tyrosine kinase (BTK) with minimal off-target activity observed in pre-clinical trials.[8],[9],[10] This potential new medicine is in development for the treatment of multiple B-cell and other cancers. The acalabrutinib development programme includes both monotherapy and combination therapy strategies in chronic lymphocytic leukaemia (CLL), MCL, Waldenström macroglobulinemia (WM), follicular lymphoma, diffuse large B-cell lymphoma, and multiple myeloma, as well as monotherapy and combination trials in solid tumours. In total, more than 25 acalabrutinib clinical trials with more than 2,000 patients are underway or have completed. Acalabrutinib was granted Orphan Drug Designation by the FDA for the treatment of patients with MCL in September 2015 and by the European Commission in March 2016 for the treatment of patients with CLL, MCL and WM. Acalabrutinib was granted Breakthrough Therapy Designation by the FDA in August 2017 for the treatment of patients with MCL who have received at least one prior therapy. Acalabrutinib is a potential new medicine not approved for any current use.

Polaris Group Announces Treatment of First Patient in Phase 2/3 Study of ADI‑PEG 20 Plus Cisplatin and Pemetrexed in Malignant Pleural Mesothelioma

On August 2, 2017 Polaris Group reported that the first patient has been dosed in its randomized, placebo-controlled, double blind phase 2/3 trial (ATOMIC-meso) in malignant pleural mesothelioma (MPM) patients (Press release, Polaris Pharmaceuticals, AUG 2, 2017, View Source [SID1234526283]). Patients will be randomized to receive ADI‑PEG 20 (pegylated arginine deiminase) or placebo in combination with pemetrexed and cisplatin (PemCis), the standard first-line treatment for MPM (NCT02029690). In addition to this global phase 2/3 study, Polaris Group is currently conducting multiple phase 1 studies, including ADI‑PEG 20 in combination with PemCis in non-small cell lung carcinoma, glioblastoma, and uveal melanoma, in combination with pembrolizumab in advanced solid tumors, and in combination with FOLFOX in hepatocellular carcinoma, gastric cancer, and colorectal cancer.

"ADI‑PEG 20 in combination with chemotherapy agents have demonstrated encouraging efficacy signals for several oncology indications in multiple phase 1 trials. We are working to pursue further investigations so we can bring effective treatments to more patients", said John Bomalaski, M.D., Executive Vice President, Medical Affairs at Polaris Pharmaceuticals, Inc.

About ADI‑PEG 20

ADI‑PEG 20 is a biologic being developed by Polaris Group to treat cancers carrying a major metabolic defect that renders them unable to internally synthesize arginine. Because arginine is essential for protein synthesis and survival of cells, these cancer cells become dependent upon the external supply of arginine to survive and grow. ADI‑PEG 20 is designed to deplete the external supply of arginine, causing arginine-dependent cancer cells to die while leaving the patient’s normal cells unharmed. Multiple cancers have been reported to have a high degree of arginine-dependency and can potentially be treated with ADI‑PEG 20.

Bolder BioTechnology Announces Initiation of Phase 1 Clinical Trial of BBT-015 for Treating Neutropenia and Acute Radiation Syndrome

On August 2, 2017 Bolder BioTechnology, Inc. reported that it has commenced dosing of patients in a Phase 1 clinical trial of its proprietary long-acting granulocyte colony-stimulating factor (G-CSF) analog, BBT-015 (Press release, Bolder BioTechnology, AUG 2, 2017, View Source [SID1234526029]). The trial is designed to study the pharmacokinetics, pharmacodynamics, safety and tolerability of single subcutaneous doses of BBT-015 in healthy human subjects. BBT-015 is being developed as a treatment for chemotherapy-related neutropenia in cancer patients and for Acute Radiation Syndrome.

Joe Cox, Ph.D., Bolder BioTechnology’s President said: "Initiation of this clinical trial represents a major milestone for Bolder BioTechnology and the culmination of many years of effort by our dedicated and talented employees."

"BBT-015 is a novel G-CSF analog that exhibits a longer duration of action and greater potency than other G-CSF products. In preclinical studies, BBT-015 stimulated larger and longer-lasting increases in neutrophils, and faster neutrophil recovery in chemotherapy-treated, neutropenic animals compared to other G-CSF products. BBT-015 also significantly increased survival and accelerated recovery of neutrophils, platelets, and red blood cells in animals exposed to lethal doses of radiation, even when administered 24 hours following radiation exposure."

"BBT-015’s increased potency and longer duration of action may stimulate faster neutrophil recovery in cancer patients and / or allow the drug to be administered less frequently and at lower doses than competing G-CSF products, with associated cost savings for patients."

"G-CSF products are some of the best selling biopharmaceuticals in the world, with annual worldwide sales exceeding $6 billion, primarily from the treatment of neutropenia in cancer patients."

About BBT-015
BBT-015 is a long-acting G-CSF analog produced using site-specific PEGylation technology. G-CSF is a human protein that stimulates production of neutrophils, a type of white blood cell that is important for fighting infections. G-CSF has a short half-life in humans and typically is administered to patients by daily injection. BBT-015 has been selectively modified with the polymer polyethylene glycol at a unique site in the protein, which allows the protein to last longer in patients, reducing the need for frequent administration and increasing the protein’s ability to stimulate long-lasting production of neutrophils.

About Chemotherapy-Related Neutropenia
Neutropenia (severely reduced numbers of neutrophils) is a common side effect of chemotherapy treatment in cancer patients. Neutropenia increases the patient’s risk of developing serious bacterial infection and requiring expensive hospitalization. G-CSF products are commonly administered to cancer patients following chemotherapy to accelerate neutrophil recovery and decrease the length of time that patients are neutropenic.

About Acute Radiation Syndrome
Acute Radiation Syndrome, often referred to as radiation sickness, is a collection of illnesses that occurs following exposure to high doses of ionizing radiation within a short period of time, such as might occur following an accident at a nuclear power plant or detonation of a nuclear weapon. Bone marrow, which is responsible for producing new blood cells, is one of the most radiation-sensitive tissues, and subjects acutely exposed to high doses of radiation typically develop bone marrow aplasia and severe neutropenia and thrombocytopenia (low numbers of platelets) within a few weeks of exposure, Many subjects die from infections due to a lack of neutrophils, or from uncontrolled bleeding due to a lack of platelets.

Consolidated Quarterly Financial Report (First Quarter)

On August 2, 2017 Eisai Co., Ltd. reported financial results for the first quarter ended June 30, 2017 (Report, Eisai, AUG 2, 2017, View Source [SID1234520053]).

Gross profit for the first quarter of 2017 was 92.5 billions of Yen in comparison to that of 87.1 billions of Yen in the first quarter of 20156. Sales of Oncology products amounted to 31.1 billions of Yen

For Eisai’s detailed sales figures, View Source

bluebird bio Reports Second Quarter 2017 Financial Results and Recent Operational Progress

On August 2, 2017 bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic diseases and T cell-based immunotherapies for cancer, reported business highlights and financial results for the second quarter ended June 30, 2017 (Press release, bluebird bio, AUG 2, 2017, View Source [SID1234520007]).

"In the first half of 2017, we’ve made tremendous progress against our stated goals and continue to build momentum to the end of the year. New data from our bb2121 anti-BCMA CAR T program reinforced our confidence in this program, and we and Celgene are moving full speed ahead to continue to the next stage of development. We presented early data demonstrating the impact of manufacturing improvements for LentiGlobin, with our first patients with TDT in Northstar-2 showing significantly higher drug product VCNs than we saw in previous studies. We also announced interim data from the first 17 patients in the Starbeam study of Lenti-D that showed 88% of those patients met the primary endpoint," said Nick Leschly, chief bluebird. "We look forward to sharing more of our progress later this year at ASH (Free ASH Whitepaper), where we will provide updated data on our TDT and multiple myeloma programs, as well as a first look at the progress made in the HGB-206 study in severe SCD with changes in the study protocol. For the rest of the year, we’re remaining laser-focused on the execution of our clinical development goals across our programs to bring our transformative therapies to patients and on preparing our organization to bring our gene therapy products to many more patients in a commercial setting."

Recent Highlights

COMPLETED ENROLLMENT IN NORTHSTAR-2 – In June, bluebird bio completed the enrollment of the adult and adolescent patient cohort in the Northstar-2 study of LentiGlobin drug product in patients with TDT and non-β0/β0 genotypes.
UPDATED DATA FROM BB2121 ANTI-BCMA CAR T PROGRAM PRESENTED – At ASCO (Free ASCO Whitepaper) in June, bluebird bio presented updated results from the ongoing CRB-401 Phase 1 clinical study of bb2121, an investigational anti-BCMA CAR T cell therapy, in 18 patients with relapsed/refractory multiple myeloma. 100% of the 15 evaluable patients in active dose cohorts (doses above 50 x 106) achieved an objective response; overall response rate (ORR) across all cohorts (n=18) was 89%. 73% of evaluable patients in active dose cohorts achieved a very good partial response (VGPR) or better; 27% complete response (CR) rate across active dose cohorts. All patients tested for minimal residual disease (MRD) status (n=4) were found to be MRD-negative. No disease progression had been observed in active dose cohorts as of the May 4, 2017 data cut-off; range of follow-up was 8 to 54 weeks. No dose-limiting toxicities had been observed. The objective of this Phase 1 dose-escalation study is to evaluate the safety and efficacy of bb2121 and determine a recommended Phase 2 dose. bluebird bio and Celgene are jointly developing bb2121.
EARLY DATA FROM NORTHSTAR-2 PRESENTED – At EHA (Free EHA Whitepaper) in June, bluebird bio presented early data from its Phase 3 Northstar-2 (HGB-207) study of LentiGlobin drug product in patients with transfusion-dependent β-thalassemia (TDT) and non-β0/β0 genotypes. Drug product vector copy number (DP VCN) and percentage of lentiviral vector positive cells (LVV+) for the initial 7 drug product lots manufactured in Northstar-2 were consistently higher than in Northstar (HGB-204), with a median DP VCN of 3.0. Initial results show that the three patients treated to date had achieved in vivo VCN and HbAT87Q production as good as or better than patients achieving transfusion independence in Northstar. The first patient treated in Northstar-2 with 6 months of follow-up achieved normal levels of total hemoglobin (13.3 g/dL) after discontinuing transfusions, producing 9.5 g/dl of HbAT87Q at last follow-up. The safety profile was consistent with autologous transplantation.
NEW DATA FROM HGB-205 PRESENTED – At EHA (Free EHA Whitepaper) in June, bluebird bio presented new data from the HGB-205 study of LentiGlobin drug product in patients with TDT and severe sickle cell disease (SCD). Ongoing transfusion independence up to 3.5 years was observed in patients with TDT; three patients have discontinued iron chelation. The first patient with SCD treated with gene therapy (Patient 1204) continues to show clinically meaningful improvement in symptoms of SCD and stable vector copy number and HbAT87Q in peripheral blood. Two recently treated patients with severe SCD show increasing levels of HbAT87Q and stable in vivo VCN. As with Patient 1204, the first patient with SCD treated in HGB-205, these two patients received a more stringent busulfan conditioning regimen and regular blood transfusions prior to stem cell harvest.
TOPLINE INTERIM LENTI-D DATA ANNOUNCED – In June, bluebird bio announced topline interim clinical data on the initial 17 patients treated in the Starbeam study of Lenti-D drug product in CALD. As of June 13, 15/17 patients (88%) in initial study cohort remain free of major functional disabilities (MFDs) at 24 months, the primary endpoint of the trial. This exceeds bluebird’s pre-defined interim efficacy benchmark for the study of MFD-free survival of 76%, derived from the literature and based on clinical data from an earlier observational study describing that natural history of CALD and outcomes from allogeneic hematopoietic stem cell transplant. The safety profile of Lenti-D was consistent with myeloablative conditioning. No patients treated with Lenti-D had graft versus host disease, and there was no graft rejection or clonal dominance. An expansion cohort is enrolling additional patients to gain European manufacturing experience.
NEW BOARD APPOINTMENTS – In June, bluebird bio appointed John O. Agwunobi, M.D. and Douglas A. Melton, Ph.D. to its Board of Directors.
DUKE COLLABORATION – In May, bluebird bio announced that it has entered into a collaboration with Duke University’s Robert J. Margolis, MD, Center for Health Policy to develop a broadly-supported path for value-based payment reform models for gene therapies and other innovative treatments.
STRENGTHENED BALANCE SHEET – In June, bluebird raised $436.8 million in net proceeds in an equity financing. The company’s cash, cash equivalents and marketable securities are sufficient to fund operations into 2020 based on the company’s current business plan. Proceeds from the equity financing will fund the potential exercise of the option to co-develop and co-promote bb2121; planned clinical studies in oncology and severe genetic diseases; and to further expand the company’s manufacturing platform and capabilities to support ongoing and anticipated product development efforts and in anticipation of a potential commercial launch; and general and administrative expenses.
Second Quarter 2017 Financial Results and Financial Guidance

Cash Position: Cash, cash equivalents and marketable securities as of June 30, 2017 were $1.2 billion, compared to $884.8 million as of December 31, 2016, an increase of $312.2 million.
Revenues: Total revenue was $16.7 million for the second quarter of 2017 compared to $1.6 million for second quarter of 2016. The increase is primarily attributable to revenue recognized under bluebird bio’s out-licensing agreements with Novartis Pharma AG and GlaxoSmithKline Intellectual Property Development Limited (GSK) and the commencement of revenue recognition for the bb2121 license and manufacturing services under the company’s agreement with Celgene.
R&D Expenses: Research and development expenses were $64.3 million for the second quarter of 2017 compared to $41.8 million for the second quarter of 2016. The increase in research and development expenses was primarily attributable to increased manufacturing expenses, clinical trial expenses, and employee-related costs due to increased headcount to support overall growth.
G&A Expenses: General and administrative expenses were $21.2 million for the second quarter of 2017 compared to $18.4 million for the second quarter of 2016. The increase in general and administrative expenses was primarily attributable to increased employee-related costs due to increased headcount, and increased facility-related expenses to support overall growth.
Net Loss: Net loss was $70.9 million for the second quarter of 2017 compared to $58.8 million for the second quarter of 2016.
Financial Guidance: bluebird bio expects that its cash, cash equivalents and marketable securities of $1.2 billion as of June 30, 2017 will be sufficient to fund its current operations into 2020.