On February 15, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported Health Canada’s approval of ZYTIGA (abiraterone acetate) in combination with prednisone and androgen deprivation therapy (ADT) for the treatment of patients with newly diagnosed, high-risk metastatic hormone-sensitive prostate cancer (mHSPC) who may have received up to three months of prior ADT (Press release, Johnson & Johnson, FEB 15, 2018, View Source [SID1234524007]).

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This latest approval is based on Phase 3 data from the pivotal LATITUDE clinical trial, a multinational, multicenter, randomized, double-blind, placebo-controlled trial (N=1,199) that examined the use of ZYTIGA 1,000 mg once daily in combination with prednisone 5 mg once daily and ADT, compared to placebos plus ADT in patients with newly diagnosed mHSPC.3 The study showed ZYTIGA, in combination with prednisone and ADT reduced the risk of death by 38 per cent compared to placebo plus ADT (median OS not reached vs. 34.7 months, respectively; HR=0.62; 95% confidence interval [CI], 0.51 to 0.76; P < 0.001) in patients with mHSPC.4

"Previously men with newly diagnosed metastatic prostate cancer have had limited options for first-line treatments," Dr. Fred Saad, Chief of Urology, Centre Hospitalier de l’Université de Montréal, Université de Montreal and LATITUDE clinical investigator.** "This latest approval for ZYTIGA is an exciting milestone for men, their caregivers and treating clinicians as it provides a new first-line treatment option for high-risk metastatic hormone-sensitive prostate cancer that improves overall survival and quality of life."

About the LATITUDE Study
The LATITUDE study, published in the New England Journal of Medicine,5 enrolled 1,199 newly diagnosed patients with high-risk mHSPC and was conducted at 235 sites in 34 countries, including sites in 10 Canadian cities and with 33 Canadian patients.6,7 A total of 597 patients were randomized within three months of diagnosis to receive ADT plus ZYTIGA and prednisone, while 602 patients were randomized to receive ADT and placebo.8 Patients were high-risk mHSPC as defined as having at least two of the three following factors associated with poor prognosis: Gleason score ≥8, ≥3 bone lesions and/or presence of measurable visceral metastases.9

Overall, the safety profile of ZYTIGA in combination with prednisone and ADT was similar to prior studies in patients with metastatic castration-resistant prostate cancer (mCRPC).10 In the LATITUDE study, patients received a lower dose of prednisone at 5 mg/day with the usual dose of ZYTIGA at 1,000 mg/day plus ADT. The most common all grade adverse reactions (≥10%) observed with ZYTIGA compared to placebo were hypertension (36.7% versus 22.1%), hypokalemia (20.4% versus 3.7%) and hot flushes (15.4% versus 12.5%).

About Prostate Cancer in Canada
Prostate cancer is a disease where prostate cells lose control of growth and division, and are no longer able to function as healthy cells.11,12 It can be slow-growing and go undetected for years.13

Prostate cancer is the most common cancer among Canadian men, with approximately 21,300 men diagnosed each year.14 Roughly 10 to 20 per cent of those living with prostate cancer will present with metastatic disease,15 in which the tumour has spread beyond the prostate to other parts of the body. There is no cure for metastatic prostate cancer.16

Metastatic hormone-sensitive prostate cancer refers to prostate cancer that still responds to testosterone suppression therapy.17 Patients with newly diagnosed metastatic disease and high-risk disease characteristics tend to have a poorer prognosis.18

About ZYTIGA
ZYTIGA blocks CYP17-mediated androgen production at three sources: in the testes, adrenals and the prostate tumour tissue.19 Androgen production left unchecked fuels the growth of prostate cancer.20

Health Canada first approved ZYTIGA in 2011 to be used in combination with prednisone for the treatment of mCRPC in patients who have received prior chemotherapy containing docetaxel after failure of ADT. In 2013, it was approved for mCRPC in patients who are asymptomatic or mildly symptomatic after failure of ADT.21

On February 15, 2018 Asterias Biotherapeutics, Inc. (NYSE American:AST), a biotechnology company dedicated to developing regenerative medicine therapeutics to treat neurological conditions associated with de-myelination and cellular immunotherapies to treat cancer, reported that it has strengthened its global IP portfolio over the past 12 months with the issuance of 46 new patents, including in the United States, Europe, Japan, Canada, China, Australia, Israel and South Korea (Press release, BioTime, FEB 15, 2018, View Source;p=RssLanding&cat=news&id=2332687 [SID1234523999]). Of the 46 patents, 38 are owned or jointly owned by Asterias and eight patents are exclusively licensed to the Company.

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Included in the issued patents are those covering differentiation of pluripotent stem cells to hematopoietic progenitors and differentiation of pluripotent stem cells to immature and mature dendritic cells, providing key patent protection to the Company’s allogeneic (non-patient specific) cancer immunotherapy AST-VAC2 program. Other issued patents cover various aspects of culture and expansion of undifferentiated stem cells, providing support for both AST-VAC2 and the Company’s AST-OPC1 product candidate which is currently being evaluated in the Company’s Phase 1/2a clinical program for severe spinal cord injury. Additional issued patents cover differentiation of pluripotent stem cells to various other lineages, including neural cells such as dopaminergic neurons, cardiomyocytes, and hepatocytes.

"We are excited about these new patents as they provide additional protection for certain aspects of the AST-VAC2 manufacturing process and support scalable processes of culturing pluripotent stem cells," said Michael Mulroy, President and Chief Executive Officer of Asterias. "In addition to being important for our own programs, these patents and our entire patent portfolio could enhance shareholder value by providing future licensing and partnering opportunities with third parties."

On February 15, 2018 Athenex (Nasdaq:ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer and related conditions, reported that the enrollment of patients is on target for the Company to be able to conduct a second interim analysis in the Oraxol KX-ORAX-001 Phase III clinical trial in the third quarter of 2018 (Press release, Athenex, FEB 15, 2018, View Source;p=RssLanding&cat=news&id=2332730 [SID1234523998]).

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Oraxol, an innovative development in the treatment of cancer, is a novel oral formulation of paclitaxel, a very effective and commonly used chemotherapy treatment for many cancers, combined with HM30181A (a novel orally non-absorbable gastrointestinal tract P-glycoprotein pump inhibitor). The Oraxol KX-ORAX-001 Phase III clinical trial is an international randomized controlled clinical trial comparing Oraxol monotherapy against intravenous (IV) paclitaxel monotherapy in patients with metastatic breast cancer, with target sample size of 360 patients. The study is designed to show superiority of clinical efficacy of Oraxol over IV paclitaxel based on independently confirmed response rates.

In accordance with the protocol the Company conducted a first interim analysis when 90 patients completed 18 weeks of treatment in October 2017. Based on that analysis, the independent Drug Safety Monitoring Board (DSMB) unanimously recommended continuation of the study. The DSMB was impressed by the conduct of the study in achieving a good overall response rate. The DSMB noticed that neuropathy was rare with Oraxol treatment. Neuropathy is a dose limiting toxicity of IV paclitaxel. The DSMB encouraged the rapid patient recruitment toward the scheduled second interim analysis at 180 patients.

Athenex has already enrolled more than 180 patients and therefore expects the second interim analysis in the third quarter of 2018.

Dr. Rudolf Kwan, Chief Medical Officer, commented, "In January 2018, we had positive feedback from the FDA that if this study meets the primary endpoint with an acceptable benefit/risk profile, it could be adequate as a single comparative trial to support registration of Oraxol for a metastatic breast cancer indication in the United States. We are looking forward to seeing results from the second interim analysis of this clinical trial."

Dr. Johnson Lau, Athenex’s Chief Executive Officer and Chairman of the Board, stated, "We are very proud of the excellent planning and execution of our clinical team. To be able to deliver both the enrollment for the Oraxol Phase III study on target time and the enrollment of two Phase III studies for KX-01 Ointment for the treatment of actinic keratosis ahead of schedule reflect the hard work, quality and the commitment of our clinical operation team. We are delighted that we are going to again deliver an interim analysis of the topline Oraxol Phase III study results on schedule as planned. Athenex is also conducting clinical studies on Oraxol in other geographic areas as well as for the expansion of clinical indications. We are also proud that Oraxol has recently obtained the Promising Innovative Medicine (PIM) designation by the United Kingdom Health Authority MHRA and also the allowance of two IND (HM30181A and oral paclitaxel capsules) by the Chinese FDA."

On February 15, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s New Drug Application (NDA) for ivosidenib (AG-120) for the treatment of patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with an isocitrate dehydrogenase 1 (IDH1) mutation (Press release, Agios Pharmaceuticals, FEB 15, 2018, View Source [SID1234523997]). The NDA was granted Priority Review and has been given a Prescription Drug User Fee Act (PDUFA) action date of August 21, 2018. The FDA’s Priority Review status accelerates the review time from 10 months to a goal of six months from the day of filing acceptance and is given to drugs that may offer major advances in treatment or may provide a treatment where no adequate therapy exists. Agios completed the NDA submission in late December 2017.

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"After decades of little change, treatment of AML has begun to shift dramatically as result of new therapies, and IDHm inhibitors will play an important role in how we treat this terrible disease," said David Schenkein, M.D., chief executive officer of Agios. "Today marks an important milestone in our efforts to rapidly advance what could be the first targeted treatment for R/R AML patients with an IDH1 mutation. We appreciate the FDA’s collaboration during the application process, and we look forward to continuing our productive dialogue."

Ivosidenib is a first-in-class, oral, targeted inhibitor of mutant IDH1. The NDA submission is based on results from AG120-C-001, a Phase 1 dose-escalation and expansion study of ivosidenib in patients with advanced hematologic malignancies and an IDH1 mutation. Data from the R/R AML patients in this study were presented at the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

Additionally, Abbott has submitted a Premarket Approval (PMA) application for the FDA review of an IDH1 assay on the Abbott m2000 RealTime System, an automated sample preparation and batch analyzer system for nucleic acid amplification and detection. In 2014, Abbott and Agios entered into an exclusive agreement under which Abbott is responsible for development and commercialization of a RealTime PCR assay for detection of the IDH1 mutation in bone marrow and blood. The Abbott assay will serve as a companion diagnostic for ivosidenib.

IDH1 mutations occur in about 6 to 10 percent of AML patients. Recent publications have highlighted the advances in the understanding of the genetics underlying AML and the need for routine mutational analysis at diagnosis and relapse.

Ivosidenib is an investigational drug that has not been approved for any use in any country.

About Acute Myelogenous Leukemia (AML)
AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and the median age at diagnosis is 68. The vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 20 to 25 percent. IDH1 mutations are present in about 6 to 10 percent of AML cases.

On February 13, 2018 Advaxis, Inc. (NASDAQ:ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of cancer immunotherapies, reported that it has submitted a conditional Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for the company’s lead Lm Technology product candidate, axalimogene filolisbac, for the treatment of adult women who progress beyond first-line therapy of persistent, recurrent or metastatic carcinoma of the cervix (PRmCC) (Press release, Advaxis, FEB 15, 2018, View Source [SID1234523996]).

"The submission of the MAA represents a significant regulatory milestone for Advaxis and the ongoing development of our Lm Technology Platform," stated Anthony Lombardo, interim Chief Executive Officer of Advaxis. "The submission is based on the improvement in 12-month survival rates observed in the Phase 2 GOG-0265 study. We feel that these data support axalimogene filolisbac as a potential therapeutic option for patients living with PRmCC who are in desperate need of new treatment options beyond first-line therapy," added Lombardo.

The MAA submission is built around data from the GOG-0265 study which examined overall survival rates in 50 women and showed a 12-month overall survival rate (primary efficacy endpoint) of 38% (n=19/50) in women with PRmCC, representing a 55% improvement over an expected, model-predicted,12-month survival rate of 24.5%.2 More than 50% of treated women in this study had previously received multiple prior lines of therapy including treatment with bevacizumab and subsequently experienced progression of their disease.2

"Despite the availability of preventative measures, metastatic cervical cancer continues to be a major public health concern associated with high mortality rates within Europe," said Mansoor Mirza, M.D., Chief Oncologist at the Copenhagen University Hospital in Denmark and Medical Director of the Nordic Society of Gynaecological Oncology (NSGO). "The results from GOG-0265 are encouraging and could represent a meaningful step forward in the care of women suffering from PRmCC, which has seen very little innovation in almost 30 years."

In the GOG-0256 study, axalimogene filolisbac was generally well-tolerated with mostly Grade 1 and 2 flu-like adverse events associated with cytokine release which were managed with standard medical care. This safety profile is consistent with the ongoing clinical experience of axalimogene filolisbac across all clinical trials.

The EMA will evaluate the totality of the data, including results from GOG-0265 as well as supportive data from other clinical trials evaluating axalimogene filolisbac. In parallel with the MAA review process, the company will continue assessing partnership opportunities for the potential commercialization of axalimogene filolisbac in Europe.

The company has also decided to align and simplify its strategy by using axalimogene filolisbac exclusively in all ongoing and planned HPV-related cancer clinical trials, including the upcoming ADVANCE trial, previously planned with ADXS-DUAL. The strategic decision to harmonize all trials to axalimogene filolisbac is based on its clinical profile to date in over 250 patients, and its demonstration of similar activity in both HPV 16 and 18 subtypes in GOG-0265. The company believes that harmonizing to a single product candidate for all HPV-related programs will streamline developmental, regulatory and commercialization strategies.

About Axalimogene Filolisbac

Axalimogene filolisbac is a targeted Listeria monocytogenes (Lm)-based investigational immunotherapy that attacks HPV-associated cancers by altering a live strain of Lm bacteria to generate cancer-fighting T cells against cancer antigens while neutralizing the tumor’s natural protections that guard the tumor microenvironment from immunologic attack.

Axalimogene filolisbac has already achieved multiple regulatory milestones, including classification as an EMA advanced therapy-medicinal product for the treatment of cervical cancer, receipt of the U.S. Food and Drug Administration (FDA) Fast Track Designation as an adjuvant therapy for treating high-risk, locally advanced cervical cancer (HRLACC), receipt of a Special Protocol Assessment agreement with the FDA for the Phase 3 AIM2CERV trial, and orphan drug designations in three HPV-associated indications (PRmCC, head and neck, and anal cancer). In addition, axalimogene filolisbac will be studied in combination with nivolumab in the ADVANCE trial, a potential registrational trial for patients with PRmCC, which is planned to begin in 2018.