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.

On February 15, 2018 AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US (known as MSD outside the US and Canada) reported that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for selumetinib, a MEK 1/2 inhibitor, for the treatment of neurofibromatosis type 1 (NF1) (Press release, AstraZeneca, FEB 15, 2018, View Source [SID1234523985]).

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NF1 is an incurable genetic condition that affects one in 3,000 births,[i] with highly-variable symptoms, including cutaneous (skin), neurological (nervous system) and orthopaedic (skeletal) manifestations. NF1 can cause secondary complications including learning difficulties, visual impairment, pain, disfigurement, twisting and curvature of the spine, high blood pressure and epilepsy. Plexiform neurofibromas (PNs) are a neurological manifestation of NF1 and arise from nerve fascicles that tend to grow along the length of the nerve. PNs occur in approximately 20-50% of NF1 patients causing pain, motor dysfunction and disfigurement.[ii]

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, at AstraZeneca, said: "Neurofibromatosis type 1 is a devastating condition that can lead to life-threatening complications. There is no known cure for neurofibromatosis and there are limited treatment options to manage symptoms."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, at MSD Research Laboratories, said: "We’re looking forward to working with our colleagues at AstraZeneca to develop selumetinib and understand how it may benefit patients with NF1."

The potential benefit of selumetinib in NF1 is being explored in the US National Cancer Institute-sponsored Phase I/II SPRINT trial in paediatric patients with symptomatic NF1-related PNs. Phase II trial results are expected later in 2018.

The FDA’s ODD programme provides orphan status to medicines that are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US.

In addition to NF1, selumetinib is being investigated in the Phase III ASTRA trial of patients who are diagnosed with differentiated thyroid cancer (DTC) following surgery and treatment with radioactive iodine. Selumetinib was granted ODD by the US FDA for the adjuvant treatment of stage III/IV DTC in 2016. It is also being explored as a monotherapy and in combination with other treatments in Phase I trials.

NOTES TO EDITORS
About neurofibromatosis type 1 (NF1)

NF1 is caused by a spontaneous or inherited mutation in the NF1 gene. The disease is associated with many symptoms, including soft lumps on and under the skin (subcutaneous neurofibromas), skin pigmentation (cafe au lait spots) and, in 20-50% of patients, tumours on the nerve sheaths (plexiform neurofibromas). These plexiform neurofibromas can cause morbidities such as pain, motor dysfunction and disfigurement. Patients with NF1 may experience a number of other complications such as learning difficulties, visual impairment, twisting and curvature of the spine, high blood pressure, and epilepsy. People with NF1 also have an increased risk of developing other cancers, including malignant brain and peripheral nerve sheath tumours, and leukaemia. Symptoms begin during early childhood, with varying degrees of severity, and can reduce life expectancy by up to 15 years.[iii]

About selumetinib

Selumetinib is an investigational MEK 1/2 inhibitor licensed by AstraZeneca from Array BioPharma Inc. in 2003.

The NF1 gene provides instructions for making a protein called Neurofibromin, which negatively regulates the RAS/MAPK pathway, helping to control cell growth, differentiation and survival. Mutations in the NF1 gene may result in dysregulations in RAS/RAF/MEK/ERK signalling, which can cause cells to grow, divide and copy themselves in an uncontrolled manner, and may result in tumour growth. Selumetinib inhibits the MEK enzyme in this pathway, potentially leading to inhibition of tumour growth.

About the AstraZeneca and MSD Strategic Oncology Collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza (olaparib), the world’s first PARP inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. The collaboration is based on increasing evidence that PARP and MEK inhibitors can be combined with PD-L1/PD-1 inhibitors for a range of tumour types. Working together, the companies will develop Lynparza and selumetinib in combination with other potential new medicines and as a monotherapy. Independently, the companies will develop Lynparza and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death

On February 15, 2018 Cancer Research UK reported that £45 million will be invested into its network of clinical trials units across the UK, one of the charity’s largest investments in clinical research to date (Press release, Cancer Research UK, FEB 15, 2018, View Source [SID1234523966]).

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"Our clinical research enables us to translate discoveries from the lab in order to improve cancer diagnostics and treatments, giving more patients the best chance of beating their disease." – Professor Charles Swanton, Cancer Research UK

Cancer Research UK’s clinical trials units (CTUs) bring together world leading researchers and clinicians to find life-saving new treatments and tests for cancer patients.

Clinical trials are the only way to find out if a new treatment is safe to use, and if it’s better than existing treatments. Each year, around 25,000 people take part in a clinical trial that’s supported by Cancer Research UK.

The huge sum will be divided over 5 years across 8 CTUs in Cardiff, Birmingham, Glasgow, Southampton, Leeds and London (at The Institute of Cancer Research, London, UCL, and Queen Mary University of London)*.

Professor Charles Swanton, Cancer Research UK’s chief clinician, said: "Our clinical research enables us to translate discoveries from the lab in order to improve cancer diagnostics and treatments, giving more patients the best chance of beating their disease.

"This is particularly important for patients with hard to treat cancers, including pancreatic, oesophageal, lung and brain tumours, where options for treatment are limited and survival rates remain poor."

Cancer Research UK’s CTUs specialise in the design, delivery and analysis of trials that bring the latest scientific developments to patients all over the UK. They’re a vital part of the charity’s research network, helping shape the clinical research landscape in the UK and internationally.

Each of the charity’s CTUs has a different specialist focus including children’s cancer trials, cancer screening, and population research.

In Birmingham, there will be dedicated funding for finding new treatments for children with cancer.

Professor Pamela Kearns, director of Birmingham’s Cancer Research UK Clinical Trials unit and Cancer Research UK’s children’s cancer expert, said: "Clinical trials are vital to test new treatments and improve the care of children with cancer. For example, within my team, with support from Cancer Research UK, we run the International BEACON** trial, testing new combinations of therapies for children and young people with a type of childhood cancer called neuroblastoma, at a stage where they have failed to respond to standard treatments.

"One question this trial is trying to answer is if a drug called bevacizumab can help treat their neuroblastoma. Bevacizumab is a type of biological therapy called a monoclonal antibody that targets the tumour’s blood supply. Doctors already treat adult cancers with this drug and we want to see if it works for children with neuroblastoma."

Trials are also helping us to find kinder treatments with fewer side effects.

Oliver Waugh, aged 54 from London, was diagnosed with tonsil cancer in 2009. As part of his treatment, he took part in a Cancer Research UK funded clinical trial which investigated a new type of radiotherapy called Intensity Modulated Radiotherapy (IMRT). Researchers wanted to find out if IMRT caused fewer side effects and if it worked as well as standard radiotherapy for head and neck cancers.***

He said: "I was really pleased to have joined because I know the side effects from regular radiotherapy could have been far more severe. My mouth started to produce saliva again not long after treatment, and I slowly started to put weight back on.

"Now I eat what I want, including curries and other spicy food and feel lucky that the high quality of my treatment has helped me lead a regular life again and I can honestly say I’m fitter than I’ve ever been.

"I feel fortunate to have been offered the chance to help medical research and I hope that many more patients like me will get to lead full and healthy lives because of these improvements in treatment."