On June 26, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY), reported that the U.S. Food and Drug Administration (FDA) has accepted a New Drug Application (NDA) and granted Priority Review for baloxavir marboxil as a single-dose, oral treatment for acute, uncomplicated influenza in patients 12 years and older (Press release, Hoffmann-La Roche, JUN 26, 2018, View Source [SID1234527464]). The FDA is expected to make a decision on approval by 24 December 2018. A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.

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"The severity of the recent flu season underscores the need for new options beyond currently available treatments, and if approved, baloxavir marboxil would be the first flu medicine with a novel proposed mechanism of action in nearly 20 years," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "Baloxavir marboxil has been shown in clinical trials to decrease the duration of symptoms with one dose, and demonstrated a significant reduction in viral shedding in just one day. We look forward to working with the FDA during the review process."

Baloxavir marboxil is a first-in-class, single-dose investigational oral medicine with a novel proposed mechanism of action designed to target the flu virus, including oseltamivir-resistant strains and avian strains (H7N9, H5N1).7,8,9 Unlike other currently available antiviral treatments, baloxavir marboxil is designed to inhibit the cap-dependent endonuclease protein within the flu virus, which is essential for viral replication.10,11

The NDA is based on results from the phase III CAPSTONE-1 study of a single dose of baloxavir marboxil compared with placebo or oseltamivir 75 mg, twice daily for five days, in otherwise healthy people with flu. Additionally, results from a placebo-controlled phase II study in otherwise healthy people with the flu is included as supporting data in the NDA.

About CAPSTONE-1
CAPSTONE-1 is a phase III multicentre, randomised, double-blind, placebo-controlled study that evaluated the efficacy and safety of baloxavir marboxil in 1,436 people in the United States and Japan. The primary endpoint of the study was time to alleviation of symptoms (TTAS), and important secondary endpoints were time to resolution of fever, time to cessation of viral shedding and the proportion of participants positive for influenza virus titre, or virus levels in the body, by time point. The study found the following results:

Baloxavir marboxil met its primary and secondary endpoints compared to placebo:
Significantly reduced the duration of flu symptoms by more than one day (median time 53.7 hours versus 80.2 hours; p<0.0001);
Significantly reduced the duration of fever by nearly a day (median time 24.5 hours versus 42.0 hours; p<0.0001);
Significantly reduced the length of time viruses continued to be released from the body (median time of viral shedding; 24.0 hours versus 96.0 hours; p<0.0001);
Significantly reduced the levels of virus in the nose and throat from 24 hours through 120 hours.
Similar efficacy results were seen between baloxavir marboxil and oseltamivir in relation to duration of symptoms and fever reduction, but significant differences were observed in time to cessation of viral shedding favouring baloxavir marboxil:
No significant reduction in duration of symptoms (median time 53.5 hours versus 53.8 hours; p=0.7560);
No significant reduction in time to resolution of fever (median time 24.4 hours versus 24.0 hours; p=0.9225);
Significantly reduced the length of time the virus continued to be released from the body (viral shedding; 24.0 hours versus 72.0 hours; p<0.0001);
Significantly reduced the levels of virus in the nose and throat at 24 hours and 72 hours.
Baloxavir marboxil was well-tolerated and had a numerically lower overall incidence of adverse events (20.7%) reported compared with placebo (24.6%) or oseltamivir (24.8%). The most common adverse events reported were diarrhoea (3.0%), bronchitis (2.6%), nausea (1.3%) and sinusitis (1.1%), and all of these adverse events occurred at a lower frequency than placebo.

About baloxavir marboxil
Baloxavir marboxil is a first-in-class, single-dose investigational oral medicine with a novel proposed mechanism of action designed to target the influenza ("flu") A and B viruses, including oseltamivir-resistant strains and avian strains (H7N9, H5N1).7,8,9 Unlike other currently available antiviral treatments, baloxavir marboxil is the first in a new class of antivirals designed to inhibit the cap-dependent endonuclease protein within the flu virus, which is essential for viral replication.

Baloxavir marboxil is being studied in an ongoing phase III development program including paediatric populations with influenza. Data from the global phase III study (CAPSTONE-2) in patients 12 years and older with a high risk of complications from influenza, as defined by the Centers for Disease Control and Prevention (CDC), will be shared at a later date.

Baloxavir marboxil was discovered by Shionogi & Co., Ltd. and is being developed globally by the Roche Group (which includes Genentech in the U.S.) and Shionogi & Co., Ltd. Under the terms of this agreement, Roche holds worldwide rights to baloxavir marboxil excluding Japan and Taiwan, which will be retained exclusively by Shionogi & Co., Ltd. Baloxavir marboxil was approved in February 2018 by the Japanese Ministry of Health, Labour and Welfare for the treatment of influenza types A and B in adult and paediatric patients and is being commercialised in Japan and marketed under the brand name Xofluza.

On June 26, 2018 Oncorena reported a completely new and potentially groundbreaking treatment for patients with metastatic kidney cancer (Press release, Oncorena, JUN 26, 2018, View Source [SID1234527466]). The company is approaching a more intense development phase that will require a full-time CEO. Lars Grundemar has served as the Chief Scientific Officer of Oncorena and he will now assume the CEO position on July 1, 2018.

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Dr. Jan Törnell has successfully led Oncorena since 2013 as part-time CEO. Because of other ongoing commitments, he is unable to fill this position full-time.

Lars Grundemar, M.D., Ph.D. has more than 20 years leadership experience from the global pharmaceutical industry with assignments in major corporations and different countries in Europe and in the US. Dr. Grundemar has been leading multiple drug development projects across various therapeutic areas, including oncology. He has established new departments and introduced novel ways to improve research and development functions.

"We are excited to work with Lars Grundemar as CEO to bring Oncorena into the clinical phase in the near future," says Bengt-Åke Bengtsson, Chairman of the Board of Oncorena. "We would also like to thank Jan Törnell for his excellent leadership through the company’s preclinical development phase."

"I am very honored over this trust and look forward to this challenge. It’s a great privilege to be able to contribute to the development of a novel therapeutic principle to combat cancer and to improve the quality of life for patients suffering from kidney cancer," says Lars Grundemar, new CEO of Oncorena.

"I strongly believe in the success for Oncorena and I’m certain that the company is in the best of hands moving forward. I will make every effort to contribute to a smooth transition for Lars Grundemar into his new role as CEO," says Jan Törnell, currently CEO of Oncorena.

For further information, please contact
Bengt-Åke Bengtsson, Chairman of the Board, Oncorena AB,
[email protected], phone +46 (0)70 746 0000

Lars Grundemar, CEO of Oncorena from July 1, [email protected],
phone +46 (0) 76 209 5518

Jan Törnell, CEO, Oncorena AB, [email protected]
phone +46 (0)70 676 0008

About kidney cancer
Approximately 1,000 patients are affected by kidney cancer annually in Sweden and around 600 of them die. 80% of the patients are between 40 and 69 years of age when they are diagnosed (median age 63 years). The disease can often be cured with surgery if detected in time, but unfortunately the diagnosis is often made when the tumor has already spread to other organs. The prognosis is then considerably less favorable and certain groups have a median survival of only approx. 1.5 years. Today the disease is treated with various types of targeted and immuno-active drugs, often with severe side effects, and standard chemotherapy drugs have only very limited effect. There is therefore a great need for new, effective and safe drugs.

About the project
The substance, orellanine, originally emanates from a mushroom and has been ingested by mistake by a number of people. The effects are well documented and are limited to the kidneys. As the target group for the treatment is patients with metastatic kidney cancer who are undergoing dialysis the side effect profile is believed to be relatively mild. Experimental studies indicate that the effect may be dramatically positive. The preclinical studies will be completed during 2018, whereupon the clinical study is expected to start in the spring of 2019. Learn more at www.oncorena.com.

On June 26, 2018 Istari Oncology, Inc., a clinical-stage biotechnology company focused on novel immuno-oncology and immunotherapy platforms for the treatment of glioblastoma and a wide variety of tumors, reported publication of the results of a Phase 1 trial of PVSRIPO in recurrent glioblastoma in The New England Journal of Medicine (NEJM) (Press release, Istari Oncology, JUN 26, 2018, View Source [SID1234527467]). This trial was conducted by The Preston Robert Tisch Brain Tumor Center at Duke.

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In this trial of 61 adult patients, overall survival at 24 and 36 months was 21%, compared to 14% at 24 months, and 4% at 36 months in matched historical controls. Three patients receiving PVSRIPO have survived beyond 60 months.

"The impressive results with PVSRIPO in this trial are the best we have seen to date in patients with recurrent glioblastoma and provide hope for these patients whose typical survival time is less than a year," said Henry S. Friedman, MD, Chief Medical Officer of Istari and James B. Powell, Jr. Professor of Neuro-Oncology and the Division Chief for Neuro-Oncology in The Preston Robert Tisch Brain Tumor Center in the Department of Neurosurgery at Duke. "Based on the observation that the receptor for PVSRIPO, CD155, is present on almost all solid tumors, we look forward to future trials in other cancers, as well as glioblastoma, both alone and in combination with other agents, as we strive to provide hope for these patients as well."

The primary objective of the Phase 1 study was to determine the toxicity profile and Phase 2 dose for intratumoral convection enhanced delivery of PVSRIPO in WHO grade IV malignant glioma (glioblastoma). The secondary objective was to estimate overall survival compared to an historical control group. From May 2012 to May 2017, 61 consecutive adult patients with recurrent WHO grade IV malignant glioma with measurable disease were enrolled in the study that evaluated seven doses. The median overall survival for all 61 PVSRIPO patients was 12.5 months compared to 11.3 months for the matched historical control group. However, the overall survival of PVSRIPO patients reached a plateau beginning at 24 months with 24- and 36-month overall survival of 21%, while the overall survival in the matched historical control continued to decline with 24-month overall survival of 14%, and 36-month overall survival of 4%. Of these survivors, two patients are beyond 70 months, and one patient is beyond 60 months.

Adverse events affecting more than 20% of patients in the dose-expansion phase included headaches (52%), pyramidal tract syndrome (hemiparesis) (50%), seizure (45%), dysphasia (28%), and cognitive disturbance (25%). The NEJM publication is available at View Source

A multi-center Phase 2 trial of PVSRIPO alone and in combination with chemotherapy in adults with recurrent glioblastoma is currently enrolling, with a primary endpoint of 24-month survival. A Phase 1 trial of PVSRIPO in pediatric patients with recurrent glioblastoma is also currently enrolling. For additional information on clinical trials with PVSRIPO, please visit View Source

Positive preclinical data for PVSRIPO has been generated in multiple solid tumor models, both alone and in combination with other agents, including checkpoint inhibitors. Phase 1 trials are currently planned for PVSRIPO in breast carcinoma and melanoma.

About PVSRIPO
PVSRIPO is the Sabin type 1 polio vaccine, genetically modified so it cannot harm or kill normal cells. PVSRIPO is a prototypic oncolytic recombinant polio virus vaccine that recognizes the poliovirus receptor CD155, which is widely expressed in neoplastic cells of all solid tumors except Burkitt’s lymphoma, and in major immune components of the tumor microenvironment. PVSRIPO has been granted Breakthrough Status and Orphan Status by the FDA.

About Glioblastoma
Glioblastoma is the most common and aggressive form of brain cancer, comprising 52% of patients with primary brain tumors. There are approximately 13,000 patients diagnosed with GBM in the United States annually and approximately 18,000 in the European Union. Despite aggressive treatment, survival for newly diagnosed glioblastoma patients is usually less than 20 months, and for patients with recurrence, which occurs in 98% of patients, survival is usually less than 12 months.

On June 25, 2018 Andarix Pharmaceuticals, a clinical stage company aimed at developing a targeted peptide therapies for hard to treat cancers, reported that it will present a poster at the Metals in Medicine Gordon Research Conference (Press release, Andarix Pharmaceuticals, JUN 25 2018, View Source [SID1234527792]) .The conference will take place June 25-29 in Andover, NH.

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The theme of the conference is: The Indispensable Role of Metals in Medical Diagnostics, Therapeutics and Beyond. Andarix will be presenting clinical findings pertaining to Tozaride, a Rhenium metal-based drug developed by the company. The conference is an opportunity for Andarix to present its innovative technology to world
leading scientists and international metal-science experts.

About Tozaride
Tozaride is a novel, best-in-class therapeutic for lung and other cancers, which is based on a radio-labeled somatostatin peptide. Early clinical studies demonstrated that Tozaride is well tolerated and that treatment can promote disease stabilization and improve overall survival in heavily pre-treated advanced lung cancer patients. Tozaride targeted radiotherapy represents a new treatment paradigm which is expected to yield
significant clinical benefits for both small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC) patients. This therapeutic stands to provide an additional treatment option for patients who are not eligible for, or who have not responded to current therapies.

On June 25, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the Phase III IMpower133 study met its co-primary endpoints of overall survival (OS) and progression-free survival (PFS) at its first interim analysis (Press release, Hoffmann-La Roche, JUN 25, 2018, View Source [SID1234527451]). The study demonstrated that initial (first-line) treatment with the combination of TECENTRIQ (atezolizumab) plus chemotherapy (carboplatin and etoposide) helped people with extensive-stage small cell lung cancer (ES-SCLC) live significantly longer compared to chemotherapy alone. The TECENTRIQ-based combination also reduced the risk of disease worsening or death (PFS) compared to chemotherapy alone. Safety for the TECENTRIQ and chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination. These data will be presented at an upcoming medical meeting.

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"These are the first positive Phase III survival results for any immunotherapy-based combination in the initial treatment of extensive-stage small cell lung cancer, a particularly difficult-to-treat type of disease," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "The clinically meaningful results from the IMpower133 study add to the growing body of evidence demonstrating that TECENTRIQ-based combinations may be an effective treatment for different types of advanced lung cancer. We look forward to working with health authorities globally to bring this potential treatment option to people with this type of disease as soon as possible."

This is the fourth positive Phase III lung cancer study evaluating a TECENTRIQ-based combination to read out this year and the fifth positive study overall. Currently, Roche has eight Phase III lung cancer studies underway evaluating TECENTRIQ alone or in combination with other medicines across different types of lung cancer.

About the IMpower133 study
IMpower133 is a Phase III, multicentre, double-blinded, randomised placebo-controlled study evaluating the efficacy and safety of TECENTRIQ in combination with carboplatin and etoposide versus chemotherapy (carboplatin plus etoposide) alone in chemotherapy-naïve people with ES-SCLC.

The study enrolled 403 people who were randomised equally (1:1) to receive:

TECENTRIQ in combination with carboplatin and etoposide (Arm A), or
Placebo in combination with carboplatin and etoposide (Arm B, control arm)

During the treatment-induction phase, people received treatment on 21-day cycles for four cycles, followed by maintenance with TECENTRIQ or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). Treatment could be continued until persistent radiographic PD or symptomatic deterioration was observed.

The co-primary endpoints were:

PFS as determined by the investigator using RECIST v1.1 in the intention-to-treat (ITT) population
OS in the ITT population
IMpower133 met its OS and PFS co-primary endpoints as per the study protocol.

About SCLC
Lung cancer is the leading cause of cancer death globally.1 Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day.1 Lung cancer can be broadly divided into two major types: non-small cell lung cancer (NSCLC) and SCLC, with SCLC accounting for approximately 15% of all lung cancer cases.2 Survival rates for people with SCLC vary depending on the stage (extent) of the cancer at the time of diagnosis.3 The five-year relative survival rate for people with stage I SCLC is approximately 31%, however, at stage IV, the five-year relative survival rate declines to approximately 2%.4

About TECENTRIQ
TECENTRIQ is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, TECENTRIQ may enable the activation of T cells. TECENTRIQ has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Currently, Roche has eight Phase III lung cancer studies underway, evaluating TECENTRIQ alone or in combination with other medicines.

TECENTRIQ is already approved in the European Union, United States and more than 70 countries for people with previously treated metastatic NSCLC and for certain types of untreated or previously treated metastatic urothelial carcinoma (mUC).