On December 29, 2017 Mylan N.V. (NASDAQ, TASE: MYL) reported that Biosimilar Trastuzumab, co-developed by Biocon Ltd. (BSE code: 532523, NSE: BIOCON) and Mylan N.V. (NASDAQ, TASE: MYL), has been approved by ANVISA, the Brazilian regulatory agency, through their partner Libbs Farmaceutica (Libbs), a leading Brazilian pharmaceutical company (Press release, Mylan, DEC 28, 2017, View Source [SID1234522788]).

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Co-developed by Biocon and Mylan, this is the first biosimilar Trastuzumab to be approved in Brazil and is indicated for the treatment of overexpressing HER2-positive metastatic breast cancer, HER2-positive early stage breast cancer and HER2-positive advanced gastric cancer. Libbs will commercialize the product in Brazil under the brand name Zedora, which will provide affordable access to a cutting-edge biologics therapy for patients in Brazil.

Dr. Arun Chandavarkar, CEO and Joint Managing Director, Biocon, said: "This marks the first approval for a biosimilar Trastuzumab by Brazil’s ANVISA and demonstrates our commitment to provide access to high-quality and affordable biologics to patients across the globe. Cancer patients in India and some emerging markets have benefited with our Trastuzumab and the approval in Brazil will enable affordable access to this critical biologic therapy for the treatment of HER2-positive breast and gastric cancers in the country. We are committed to make global impact with our affordable antibodies against cancer."

Mylan CEO Heather Bresch commented: "The number of women diagnosed with breast cancer in Brazil is increasing. Sadly, many of the women with HER2-positive metastatic breast cancer in Brazil do not have access to Trastuzumab through the country’s public health system. The approval of Zedora, Brazil’s first Trastuzumab biosimilar, is an important step in our efforts to increase access to this critical product for patients with certain breast and gastric cancers and reduce the overall financial burden for health systems around the world."

Alcebíades de Mendonça Athayde Júnior, Libbs CEO, said: "The approval of Zedora will allow us to bring this first-of-its-kind biosimilar Trastuzumab to breast and gastric cancer patients in Brazil. Biosimilar Trastuzumab, co-developed by Biocon and Mylan, can help expand cancer­patient access to more affordable treatment and contribute to significant savings to Brazil’s healthcare system. Zedora will strengthen our current product portfolio as a new generation targeted therapy that can benefit cancer patients immensely."

Biocon and Mylan are responsible for the development of biosimilar Trastuzumab. While currently the trastuzumab will be manufactured by Biocon and supplied to Libbs for commercialization in Brazil; over a period of time the technology will be transferred to Libbs and the public partner Butantan through a Productive Development Partnership (PDP). Libbs have already built the biotechnological site to manufacture Zedora for the Brazilian market.

This is a significant approval as it sets the stage for the entry of our biosimilar Trastuzumab into Brazil, which is among the top three emerging markets globally for Trastuzumab. The pharmaceutical market in Brazil is predicted to grow to US$30 billion in 2021 from US$26 billion in 2016. (Source:GlobalData)

Breast cancer is the leading cause of cancer death in women in Brazil, where new cases are estimated to be over 57,000 annually, with an estimated incidence of 56 cases per 100,000 women. It is the second-most common type of cancer that affects women in Brazil, after non-melanoma skin cancer*. Trastuzumab is now included on the WHO list of essential medicines.

Earlier this month, Biocon and Mylan marked a major milestone with the U.S. Food and Drug Administration approval of their biosimilar Trastuzumab. Biocon and Mylan’s biosimilar Trastuzumab is also under review by regulatory authorities in Australia, Canada, Europe and several additional markets. It is already approved in several other countries around the world, including India, where it is providing increased access to this more affordable biologic for cancer patients.

About Biocon and Mylan Partnership
Mylan and Biocon are exclusive partners on a broad portfolio of biosimilar and insulin products. Our biosimilar Trastuzumab is one of the six biologic products co-developed by Mylan and Biocon for the global marketplace. Mylan has exclusive commercialization rights for the product in the U.S., Canada, Japan, Australia, New Zealand and in the European Union and European Free Trade Association countries. Biocon has co-exclusive commercialization rights with Mylan for the product in the rest of the world.

On December 28, 2017 Odonate Therapeutics, Inc. (NASDAQ: ODT), a pharmaceutical company dedicated to the development of best-in-class therapeutics that improve and extend the lives of patients with cancer, reported that it has initiated CONTESSA, a multinational, multicenter, randomized, Phase 3 study of tesetaxel in patients with locally advanced or metastatic breast cancer (MBC) (Press release, Odonate Therapeutics, DEC 28, 2017, View Source [SID1234522794]).

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Tesetaxel is an investigational, orally administered chemotherapy agent that belongs to a class of drugs known as taxanes, which are widely used in the treatment of cancer. Currently available taxanes must be delivered intravenously, typically at an infusion center. Tesetaxel has several potential therapeutic advantages over currently available taxanes, including oral administration with a low pill burden and a patient-friendly dosing regimen and a formulation that does not contain solubilizing agents that are known to cause hypersensitivity (allergic) reactions. More than 500 patients have been treated with tesetaxel across 22 clinical studies. In patients with MBC, tesetaxel was shown to have robust single-agent antitumor activity in two, multicenter, Phase 2 studies.

CONTESSA will compare tesetaxel dosed orally at 27 mg/m2 on the first day of a 21-day cycle plus a reduced dose of capecitabine (1,650 mg/m2/day dosed orally on days 1-14 of a 21-day cycle) to the approved dose of capecitabine alone (2,500 mg/m2/day dosed orally on days 1-14 of a 21-day cycle) in approximately 600 patients randomized 1:1 with human epidermal growth factor receptor 2 (HER2) negative, hormone receptor (HR) positive MBC previously treated with a taxane in the neoadjuvant or adjuvant setting. Capecitabine is an oral chemotherapy agent that is considered a standard-of-care treatment in MBC. Where indicated, patients must have received an anthracycline and/or endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor. The primary endpoint is progression-free survival (PFS) assessed by an Independent Radiologic Review Committee (IRC). CONTESSA’s secondary efficacy endpoints are overall survival, objective response rate (ORR) assessed by IRC, disease control rate (ORR + prolonged (≥ 24 weeks) stable disease) assessed by IRC and patient-reported outcomes.

"Despite recent advances in the treatment of advanced breast cancer, there remains a significant need for new therapies that allow patients to maintain a better quality of life," said Kevin Tang, Chairman and Chief Executive Officer of Odonate. "CONTESSA is designed to evaluate the potential benefit of an all-oral regimen that combines tesetaxel with a reduced dose of capecitabine as compared to the approved dose of capecitabine alone, with the goal of establishing a new, all-oral treatment option with an improved benefit-risk profile."

About Breast Cancer and Its Treatment

Breast cancer is the second most common cancer worldwide, with an estimated 1.8 million new cases diagnosed per year.1 In Europe, an estimated 494,000 new cases are diagnosed and approximately 143,000 women will die of the disease each year, making it the leading cause of cancer death in women.1 In the U.S., an estimated 255,000 new cases are diagnosed and approximately 41,000 women will die of the disease each year, making it the second-leading cause of cancer death in women.2 The 5-year survival rate for patients with metastatic breast cancer is approximately 22%.2

Breast cancer is a heterogeneous disease comprised of several molecular subtypes, which are commonly grouped into clinical subtypes based on receptor status. Human epidermal growth factor receptor 2 (HER2) negative, hormone receptor (HR) positive disease, which represents the majority of all MBC cases, remains an area of high unmet medical need. Over the past two decades, only modest survival benefits have been achieved in this patient population; hence, treatment goals emphasize controlling disease-related symptoms, minimizing toxicity and maximizing quality of life.

Patients with HER2 negative, HR positive MBC are typically treated with endocrine therapy (with or without targeted agents such as a cyclin-dependent kinase ("CDK") 4/6 inhibitor), chemotherapy, or both. The recently approved CDK 4/6 inhibitor palbociclib, an orally administered therapy, has significantly improved outcomes for patients with MBC when used in combination with endocrine agents. However, virtually all MBC patients on endocrine therapy will eventually progress and require subsequent treatment with chemotherapy. Chemotherapy agents currently available for the treatment of HER2 negative, HR positive MBC, including the oral agent, capecitabine, and the approved taxanes, generally are limited by their toxicity and impact on quality of life.

About Taxanes

Taxanes are an established class of anticancer agents that are broadly used in various cancers, including breast cancer. While paclitaxel and docetaxel, the first two taxanes approved for the treatment of breast cancer, possess robust antitumor activity, they have low oral bioavailability and low solubility. Therefore, these pharmaceutical agents must be delivered intravenously, typically at an infusion center, and also are formulated with solubilizing agents that are known to cause hypersensitivity reactions. Nab-paclitaxel, a different formulation of paclitaxel that also is approved for the treatment of breast cancer, has a greatly reduced risk of hypersensitivity reactions, but must still be delivered intravenously. Therapies given intravenously at an infusion center often are associated with: fear of needles and complications associated with venous access; anxiety, including institutional-triggered side effects such as nausea and vomiting; heightened awareness of life-threatening disease presence; and disruption of daily activities.3,4

About Tesetaxel

Tesetaxel is an investigational, orally administered chemotherapy agent that belongs to a class of drugs known as taxanes, which are widely used in the treatment of cancer. Tesetaxel has several potential therapeutic advantages over currently available taxanes, including oral administration with a low pill burden and a patient-friendly dosing regimen and a formulation that does not contain solubilizing agents that are known to cause hypersensitivity (allergic) reactions. More than 500 patients have been treated with tesetaxel across 22 clinical studies. In patients with locally advanced or metastatic breast cancer (MBC), tesetaxel was shown to have robust single-agent antitumor activity in two, multicenter, Phase 2 studies.

About CONTESSA

Odonate recently initiated CONTESSA, a multinational, multicenter, randomized, Phase 3 study of tesetaxel, an investigational, orally administered taxane, in patients with locally advanced or metastatic breast cancer (MBC). CONTESSA will compare tesetaxel dosed orally at 27 mg/m2 on the first day of a 21-day cycle plus a reduced dose of capecitabine (1,650 mg/m2/day dosed orally on days 1-14 of a 21-day cycle) to the approved dose of capecitabine alone (2,500 mg/m2/day dosed orally on days 1-14 of a 21-day cycle) in approximately 600 patients randomized 1:1 with human epidermal growth factor receptor 2 (HER2) negative, hormone receptor (HR) positive MBC previously treated with a taxane in the neoadjuvant or adjuvant setting. Capecitabine is an oral chemotherapy agent that is considered a standard-of-care treatment in MBC. Where indicated, patients must have received an anthracycline and/or endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor. The primary endpoint is progression-free survival (PFS) assessed by an Independent Radiologic Review Committee (IRC). CONTESSA’s secondary efficacy endpoints are overall survival, objective response rate (ORR) assessed by IRC, disease control rate (ORR + prolonged (≥ 24 weeks) stable disease) assessed by IRC and patient-reported outcomes. To learn more, please visit www.contessastudy.com.

On December 27, 2017 Kazia Therapeutics Limited (ASX: KZA, NASDAQ: KZIA) and Noxopharm Limited (ASX: NOX) reported the creation of a collaboration to support the future development of the Noxopharm lead program, NOX66 (Press release, Kazia Therapeutics, DEC 27, 2017, View Source [SID1234538107]).

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Under the terms of the collaboration, Kazia will provide certain technical information and related proprietary information that is expected to assist and expedite the successful development of NOX66. In return, Kazia has agreed to take a small equity interest in Noxopharm, which will help to align the future interests of both companies.

Kazia CEO, Dr James Garner, commented, "we are delighted to facilitate the future success of NOX66, and we look forward to assisting and following the progress of the program with keen interest."

Noxopharm CEO, Dr Graham Kelly, commented, "the collaboration with Kazia helps to ensure that the major clinical program planned in 2018 for NOX66 will proceed smoothly and with certainty. We look forward to providing our shareholders with data as the various clinical studies progress."

On December 27, 2017 LIDDS reported that it has successfully completed the first steps in one of its projects assessing the feasibility of using the NanoZolid drug delivery technology for intratumoral immunotherapy with positive results (Press release, Lidds, DEC 27, 2017, View Source [SID1234555921]).

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In one of LIDDS immune-oncology projects, an immune-stimulatory agent was successfully formulated using the NanoZolid drug delivery technology. Chemical analytical methods demonstrated that the agent had a very promising release profile from the drug formulation. In a second step, the NanoZolid formulated immune-stimulatory agent was tested in an immuno-oncology model of a aggressive/hard to treat cancer in mice. In this model, a single dose of the locally delivered immunotherapy significantly reduced tumour growth and increased survival in the treated animals compared to control animals.

This demonstrates that that the NanoZolid drug delivery technology can be leveraged to develop novel immunotherapies that can act locally or intratumorally.

A locally delivered immunotherapy has the potential to act either as a monotherapy or in combination with systemic immunotherapies e.g. checkpoint inhibitors. A successful combination treatment could significantly increase the response rates and efficacy rates of current immunotherapies.

A recent review article in the highly ranked journal Annals of Oncology (Impact Factor 11.855) highlights the unique opportunity of intratumoral treatments to increase the efficacy of immunotherapy while reducing the potential side-effects.

Results from the other preclinical feasibility studies are expected in the first quarter of 2018.

Immunotherapy for the treatment of cancer aims to activate and utilize the body’s own immune system to recognize and attack tumors and cancer cells and is today the fastest growing and most promising area of cancer research.

On December 27, 2017 Diffusion Pharmaceuticals Inc. (NASDAQ:DFFN) ("Diffusion" or "the Company"), a clinical-stage biotechnology company focused on extending the life expectancy of cancer patients, reported that a Phase 3 clinical trial using its lead small molecule trans sodium crocetinate ("TSC") in patients with newly-diagnosed inoperable glioblastoma multiforme ("GBM") brain cancer, is now open for enrollment (Press release, Oncolytics Biotech, DEC 27, 2017, View Source [SID1234522778]). The trial, which has been named INTACT (INvestigating Tsc Against Cancerous Tumors), follows a previous Phase 2 GBM study in which the inoperable patient subgroup showed a nearly four-fold increase in survival compared with historical controls when TSC was added to their treatment regimen (40% alive at two years vs. 10.4%). TSC’s innovative mechanism of action affects the tumor micro-environment, making treatment-resistant cancer cells more susceptible to the tumor-killing power of conventional radiation therapy ("RT") and chemotherapy (temozolomide) by re-oxygenation of the hypoxic portion of the tumor. The Company believes that a largely intact GBM tumor vasculature with limited surgical resection is conducive to TSC’s tumor re-oxygenation properties, and that this contributed to the survival increase in the Phase 2 GBM inoperable patient subgroup.

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The trial will screen 300 patients and enroll 264 in an effort to ensure that results from 236 patients will be available for analysis. Enrolled patients will be randomized in a 1:1 ratio into treatment and control groups. Patients in the treatment group will receive standard of care ("SOC") temozolomide and RT plus an intravenous bolus of TSC administered shortly before their SOC treatments. Patients in the control group will receive SOC alone. The study will compare overall survival at two years between patients in the two groups. Up to 100 clinical sites in the U.S. and Europe are expected to participate. The Company projects that enrollment will be completed by early 2019, with interim safety and efficacy data possible in 2020 and trial completion in 2021. Further site initiation is on-going, with first patient enrollment targeted for January 2018.

"Given the dire prognosis of inoperable GBM brain cancer, we are especially gratified to have the INTACT clinical trial open for enrollment. We believe that TSC can provide new hope for these patients, whose treatment options are so limited," said David Kalergis, Chief Executive Officer of Diffusion Pharmaceuticals. "The four-fold increase in inoperable GBM patients alive at two years in our Phase 2 trial is a particularly strong efficacy signal, and informs the design of our Phase 3 trial."

About the GBM Phase 3 INTACT Trial

The INTACT clinical trial is an open-label, randomized, controlled, Phase 3 safety and efficacy registration trial. Subjects will be randomized at baseline to SOC for first-line treatment of GBM plus TSC, or to SOC alone. The SOC for GBM is temozolomide plus RT for 6 weeks followed by 28 days of rest, followed by 6 cycles of post-radiation temozolomide treatment.

TSC will be administered during both the RT and post-radiation temozolomide treatment periods to those subjects so randomized.

During the RT treatment period subjects will receive:

Focal RT delivered as 60Gy/30 fractions scheduled at 2Gy/day for 5 days each week (Monday through Friday) for 6 weeks.
Temozolomide 75 mg/m2 orally once daily (usually administered the night preceding each RT session) starting the evening before the first RT session over a period of 42 calendar days with a maximum of 49 days.
TSC 0.25 mg/kg IV for 3 days each week (e.g., Monday, Wednesday, Friday, or other schedule that supplies a minimum 3 TSC doses per week) administered between 45 to 60 minutes prior to each RT session.
During the 28-day rest period all subjects will receive no treatment.

During the post-radiation 6-cycle temozolomide treatment period:

All subjects will receive 28-day oral temozolomide (150 mg/m2 first cycle and 200 mg/m2 all subsequent cycles as tolerated) administered on Day 1-5 (Monday through Friday) of each 28-day cycle.
Controls will receive oral temozolomide at night at home per the SOC and are not required to attend clinic visits during this period.
Subjects randomized to TSC will receive TSC 1.5 mg/kg (or another dose if recommended by the DSMB) 1.5 to 2 hours before their temozolomide dose during the daytime for 3 days during the first week of each 28-day cycle (Days 1, 3, and 5; e.g., Monday, Wednesday, Friday or other schedule that supplies at minimum 3 TSC doses per week). The Tuesday, Thursday doses will be given at night at home. Long-acting antiemetics may be administered prior to daytime temozolomide dosing on Days 1, 3, 5.
The safety, tolerability and pharmacokinetics ("PK") of TSC at higher doses than 0.25 mg/kg with temozolomide will be assessed during adjuvant therapy. TSC at doses between 0.25 mg/kg and up to 1.5 mg/kg in combination with concomitant temozolomide will be assigned (not randomized) in the first 8 subjects enrolled in the INTACT trial. These patients will undergo RT plus temozolomide plus TSC treatment (0.25 mg/kg) for 6 weekly cycles followed by 4 weeks of rest in standard fashion. At the Week 10 clinic visit the same 8 subjects will be assigned to treatment, with 2 subjects each assigned to TSC at doses of 0.25, 0.50, 1.0, and 1.5 mg/kg. These subjects will be studied in parallel for 2 28-day cycles with inclusion of appropriate blood sampling collection for TSC and temozolomide PK. The Data Safety Monitoring Board ("DSMB") will examine the resultant safety data after 2 cycles (Weeks 11 through 18 of post-radiation temozolomide treatment period; Days 1 to 56). The DSMB may recommend continued use of the 1.5 mg/kg TSC dose for the post-radiation temozolomide treatment period, or may prescribe another dose based on their observations. Subjects then entering into the INTACT trial will be randomized at baseline between TSC plus SOC, or SOC alone.

Further details about the trial protocol will be available shortly at www.clinicaltrials.gov.

The baseline assessment for determining progression-free survival ("PFS"), overall response rate ("ORR") and to rule out pseudo-progression, will be at 10 weeks via MRI using the "modified Response Assessment in Neuro-Oncology" ("mRANO") scale. The hazard ratio for the trial will be 0.67, which corresponds to 22% two-year survival in the TSC arm, the lower limit of the 95% confidence interval for the biopsy-only subjects in Diffusion’s Phase 2 trial, and 10% survival in the SOC arm. The estimated median survival is therefore 10 months for the SOC arm vs. 14.9 months for the TSC plus SOC arm. In order to achieve 80% power, the trial requires 118 subjects in each arm.

The study will achieve the designed 80% statistical power at 198 events, where an event is defined as death. The first analysis will occur at the earlier of two years follow-up for all subjects or 198 events. If the first analysis is at 198 events, the analysis will be a standard 2-sided stratified log-rank test at the α=0.05 significance level. If the first analysis is at two years, the Company will perform the analysis using the O’Brien-Fleming Method.

About Treatment-Resistant Cancers and TSC

Oxygen deprivation at the cellular level (hypoxia) is the result of rapid tumor growth, causing the tumor to outgrow its blood supply. Cancerous tumor cells thrive with hypoxia and the resultant changes in the tumor microenvironment cause the tumor to become resistant to RT and chemotherapy. Using a novel, proprietary mechanism of action, Diffusion’s lead drug TSC appears to counteract tumor hypoxia – and therefore treatment resistance – by safely re-oxygenating tumor tissue, thus enhancing tumor kill and potentially prolonging patient life expectancy. Oxygen levels of normal tissue appear to remain unaffected upon administration of TSC.