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Chugai announcement: Avastin approved for additional indication of advanced or recurrent cervical cancer

On May 23, 2016 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it gained approval by the Japanese Ministry of Health, Labour and Welfare (MHLW) on May 23, 2016, for "advanced or recurrent cervical cancer," as new additional indication for the anti-cancer agent / anti-VEGF humanized monoclonal antibody, "AVASTIN I.V. Infusion 100 mg/4 mL and 400 mg/16 mL" [generic name: bevacizumab (genetic recombinant) for Infusion] (Avastin) (Press release, Hoffmann-La Roche , MAY 24, 2016, View Source [SID:1234512741]).

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In Japan, Avastin is currently marketed for the indications of "unresectable advanced or recurrent colorectal cancer," "unresectable advanced or recurrent non-squamous non-small cell lung cancer," "inoperable or recurrent breast cancer," "malignant glioma" and "ovarian cancer." On September 14, 2015, Avastin for advanced or recurrent cervical cancer has been designated as orphan drug and priority review product.
This approval was obtained based on the results of overseas phase III studies (The GOG-0240 study) and Japanese phase II study (The JO29569 study).

The GOG-0240 study evaluated the efficacy and safety profile of standard chemotherapies (paclitaxel and cisplatin or paclitaxel and nogitecan) with or without Avastin in 452 patients with persistent, recurrent or metastatic cervical cancer.

– The study met its primary endpoint of improving overall survival (OS) with a statistically significant 26 percent reduction in the risk of death, representing a median gain in survival of 3.9 months, compared with those who received chemotherapy alone [16.8 months vs. 12.9 months; HR=0.74, stratified log-rank test, one-sided p=0.0066 (significance level: 0.0140)]

– The study showed that patients who received Avastin plus chemotherapy had a significant improvement of progression free survival (PFS) compared with those who received chemotherapy alone ［8.3 months vs. 6.0 months; HR=0.66, stratified log-rank test, p<0.0001.

– The study showed that patients who received Avastin plus chemotherapy had a significantly higher rate of tumor shrinkage (objective response rate, ORR) compared with those who received chemotherapy alone [45.4% (95% CI: 38.8-52.1%) vs. 33.8% (95% CI 27.6-40.4%); Chi-squared test, p=0.0117].

– The safety profile in the study was consistent with previous reports of Avastin, except for an increase in gastrointestinal-vaginal fistulas observed in patients who received Avastin plus chemotherapy compared to those who received chemotherapy alone (8.3% vs. 0.9% respectively). All patients with gastrointestinal-vaginal fistulas had a history of prior pelvic radiation.

The JO29569 study evaluated the tolerability, safety and efficacy of Avastin plus paclitaxel and cisplatin. Within eight Japanese patients with advanced or recurrent cervical cancer enrolled in the study, seven patients were evaluated, and one patient was excluded before the start of the study. As a result, the tolerability of Avastin plus chemotherapy was confirmed, and the harmful phenomenon to become the problem was not accepted, and no new safety finding were observed.

"We are proud that Avastin received an approval for cervical cancer as the sixth indication in Japan, which will contribute to the treatment of many cancer patients," said Chugai’s Director and Executive Vice President, Dr. Yutaka Tanaka. "We believe that Avastin would bring great news for the treatment of advanced or recurrent cervical cancer, which has limited treatment options and has not seen any progress for the last ten years."

Avastin is approved in Europe for the treatment of advanced stages of breast cancer, colorectal cancer, non-small cell lung cancer, renal cell cancer, ovarian cancer and cervical cancer, and is available in the US for the treatment of colorectal cancer, non-small cell lung cancer, renal cell cancer, recurrent glioblastoma, cervical cancer and recurrent ovarian cancer. Avastin is approved for cervical cancer in 67 countries (as of January, 2016).

The number of patients newly diagnosed as cervical cancer in Japan continues to rise each year and the annual average in 2015-2019 is estimated to be approximately 10,600.*

As the top pharmaceutical company in the field of oncology in Japan, Chugai is convinced that Avastin can contribute to the treatment of patients with "advanced or recurrent cervical cancer," a disease with high unmet medical need, by providing a new therapeutic option.

Drug Information
The underlined descriptions are newly added.
Brand name: Avastin for intravenous infusion 100 mg/4 mL
Avastin for intravenous infusion 400 mg/16 mL
Generic name: bevacizumab (genetic recombination)
Indications, dosage and administration:
Indications Dosage and Administration Unresectable advanced or recurrent colorectal cancer The usual adult dosage is 5 mg/kg (body weight) or 10 mg/kg (body weight) of bevacizumab (recombinant) per intravenous infusion in combination with other antineoplastic agents. The administration interval of AVASTIN should be 2 weeks or longer. The usual adult dosage is 7.5 mg/kg (body weight) of bevacizumab (recombinant) per intravenous infusion in combination with other antineoplastic agents. The administration interval of AVASTIN should be 3 weeks or longer. Unresectable advanced or recurrent non-squamous nonsmall cell lung cancer The usual adult dosage is 15 mg/kg (body weight) of bevacizumab (recombinant) per intravenous infusion in combination with other antineoplastic agents. The administration interval of AVASTIN should be 3 weeks or longer. Ovarian cancer Advanced or recurrent cervical cancer Inoperable or recurrent breast cancer The usual adult dosage is 10 mg/kg (body weight) of bevacizumab (recombinant) per intravenous infusion in combination with paclitaxel. The administration interval of AVASTIN should be 2 weeks or longer. Malignant glioma The usual adult dosage per intravenous infusion of bevacizumab (recombinant) is 10 mg/kg (body weight) every 2 weeks or 15 mg/kg (body weight) every 3 weeks. The administration interval of AVASTIN should be appropriately extended on the basis of patient condition. Drug prices: Avastin for intravenous infusion 100 mg/4 mL JPY 41,738/vial Avastin for intravenous infusion 400 mg/16 mL JPY 158,942/vial

OXiGENE Announces Results of Phase 2 Study of CA4P in Recurrent Ovarian Cancer Published in Journal of Clinical Oncology

On May 24, 2016 OXiGENE, Inc. (Nasdaq:OXGN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, reported the online publication of results from Study GOG-0186I in the Journal of Clinical Oncology, the official journal of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, OXiGENE, MAY 24, 2016, View Source [SID:1234512739]).

This is the first published report of the beneficial effects of combination vascular targeted therapy (VTT) for women with recurrent ovarian cancer. The open-label randomized phase 2 study in the U.S. enrolled a total of 107 patients at 67 sites to receive either CA4P (fosbretabulin) plus bevacizumab (CA4P combination) or bevacizumab alone (control). The Gynecologic Oncology Group (GOG), a member of NRG Oncology, conducted the study with support from the National Cancer Institute.

"I’m excited about the therapeutic potential of CA4P when used in combination with bevacizumab for the treatment of recurrent ovarian cancer," stated Bradley J. Monk, M.D., Director of the Division of Gynecologic Oncology at St. Joseph’s Hospital and Medical Center and the Principal Investigator of the study. "In this randomized Phase 2 trial, the combination including CA4P prolonged progression free survival (PFS) compared to bevacizumab alone, and preliminary data show it also improved overall survival for these women. In addition, the safety profile of combination vascular targeted therapy, including hypertension, was acceptable with appropriate management. I look forward to further studying this promising therapeutic approach in the upcoming FOCUS trial."

As OXiGENE previously reported, the study met its primary endpoint by demonstrating a statistically significant improvement in PFS for patients receiving the CA4P combination compared to the control (7.3 vs 4.8 months, respectively; Hazard Ratio (HR)=0.69; p=0.05 pre-specified one-sided analysis). Treatment emergent adverse events (AEs) associated with the CA4P combination were relatively low, and no serious AEs were observed. The most common AE associated with CA4P combination was hypertension, occurring in 18 patients (35%) compared to 10 patients (20%) in those receiving control (grade 3 and above).

New findings from the publication include:

Preliminary median overall survival (OS) was longer for patients receiving the CA4P combination than for the control (24.6 vs to 22.0 months, respectively; HR=0.85; data as of April 2015).
The improvement in PFS for patients receiving the CA4P combination was greater for patients with measurable disease than it was for patients without measurable disease, suggesting — along with the findings of improved PFS in patients with platinum-resistant disease — that CA4P combination therapy is more effective in those with more advanced disease.

Additional key information included in the publication include:

More patients receiving the CA4P combination compared to the control were alive and without disease progression at the completion of the study (13 (24.1%) vs. 6 (11.3%), respectively).
The relative probability of responding to treatment was 41% greater for the CA4P combination compared to control.
Inducing tumor vascular collapse with CA4P and concurrently preventing vessel regrowth with bevacizumab reduced the risk of tumor progression by an estimated 31.5%.

"We are very pleased that the data from the GOG-0186I Study are now available for the medical community," stated William D. Schwieterman, M.D., OXiGENE’s President and Chief Executive Officer. "The initial results showing an overall survival benefit for CA4P-treated patients potentially signify a much needed therapeutic advance for women with recurrent ovarian cancer, and we look forward to conducting additional analyses on this important outcome as the data mature."

Evotec extends integrated drug discovery alliance with Genentech

On May 24, 2016 Evotec AG (Frankfurt Stock Exchange: EVT, TecDAX, ISIN: DE0005664809) reported that Genentech, a member of the Roche Group, has extended its integrated drug discovery alliance with Evotec for a further three years to discover novel small molecule therapeutics (Press release, Evotec, MAY 24, 2016, View Source [SID:1234512721]).

The collaboration initiated in May 2010 was renewed in 2013 and this second extension further validates the value of Evotec’s state-of-the-art technology platform and broad expertise in drug discovery. Activities performed within the collaboration include pharmacology, screening, chemistry, proteomics and structural biology.

Dr Mario Polywka, Chief Operating Officer of Evotec, commented: "We are delighted that once again we have extended this fruitful collaboration beyond its 7th year and this latest extension is validation of the value Evotec brings to this partnership. With an increasing portfolio of activities, the scientific teams from both companies are working closely together to effectively and efficiently advance Genentech’s discovery projects."

No financial details were disclosed.

Fortress Biotech Presents Positive Data from Phase 1/2 Study

On May 24, 2016 Fortress Biotech reported positive data from its phase I/II study of CNDO-109- activated allogeneic natural killercells in acute myeloid leukemia (AML) (Press release, UCLB, MAY 24, 2016, View Source [SID:1234512720]).

Originally developed in the laboratory of Professor Mark Lowdell from the UCL Department of Haematology,biopharmaceutical company Fortress Biotech obtained exclusive worldwide rights from UCL Business PLC to develop and commercialise CNDO-109, a lysate (disrupted CTV-1 cells, cell membrane fragments, cell proteins and other cellular components) that activates donor NK cells ex vivo.

AML is a cancer of the myeloid line of blood cells characterised by the rapid growth of abnormal white blood cells. Once diagnosed with AML, patients typically receive induction and consolidation chemotherapy, with the majority achieving complete remission. However, roughly 70 to 80 per cent of patients who first complete remission will relapse, and the overall five-year survival rate is less than 25 per cent.

With three high-risk patients treated at the higher dose units having remained in complete remission for two years, data suggest that CNDO-109-activated allogeneic natural killer cells are safe and well-tolerated, and capable of extending complete remissions in high-risk acute myeloid leukemia patients.

MorphoSys and MD Anderson Cancer Center Join Forces for the Development of Novel Oncology Therapeutics

On May 24, 2016 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) and The University of Texas MD Anderson Cancer Center reported a long-term strategic alliance for the discovery and development of novel therapeutic antibodies against cancer (Press release, MorphoSys, MAY 24, 2016, View Source [SID:1234512718]).

MorphoSys will work with MD Anderson’s Oncology Research for Biologics and Immunotherapy Translation (ORBIT) unit, a platform of MD Anderson’s Moon Shots Program with a combination of industry and academic science expertise in the development of monoclonal antibodies.

Collaborating on numerous targets in a variety of oncology indications, the partners will work together to identify, validate and develop novel anti-cancer antibodies through to clinical proof of concept. MorphoSys will apply its proprietary Ylanthia technology to generate and optimize fully human antibody candidates against jointly selected targets. The parties will collaborate in target validation and preclinical drug development to quickly bring selected candidates into the clinic.

"We are excited to join forces with MD Anderson, one of the world’s most respected cancer research and care institutions, to work on bringing cancer treatment to a new level," said Dr Simon Moroney, Chief Executive Officer of MorphoSys. "This partnership combines MD Anderson’s expertise with our strength in developing innovative antibodies based on our Ylanthia technology platform. This deal is another step in the execution of our strategy of building an oncology pipeline of optimized therapeutic antibodies against innovative targets, with the goal of improving outcomes for cancer patients."

MD Anderson also will conduct in collaboration with MorphoSys early clinical trials of therapeutic antibody candidates with the goal of obtaining proof of concept, utilizing its translational medicine capabilities to optimize development.

"ORBIT is committed to bringing ground-breaking monoclonal antibodies into the clinic that can significantly benefit cancer patients", said Carlo Toniatti, M.D., Ph.D., executive director of ORBIT. "This alliance is designed to complement our drug discovery and clinical strengths and quickly and effectively develop potentially disruptive anti-cancer therapies for patients worldwide."

The long-term collaboration, licensing and co-development alliance will embrace multiple targets and programs. During the five-year research phase of the partnership, the parties will select innovative targets and apply their respective expertise and technologies to generate and validate antibody candidates against these targets. During the development phase of the collaboration, the parties will jointly develop antibodies through clinical proof of concept. Thereafter, MorphoSys has options to continue development of selected antibodies through later clinical stages.