On May 23, 2016Exelixis, Inc. (NASDAQ:EXEL) reported positive top-line results from the CABOSUN randomized phase 2 trial of cabozantinib in patients with previously untreated advanced renal cell carcinoma (RCC) (Press release, Exelixis, MAY 23, 2016, View Source [SID:1234512708]).

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The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for cabozantinib compared with sunitinib in patients with advanced intermediate- or poor-risk RCC. The safety data in the cabozantinib-treated arm of the study were consistent with those observed in previous studies in patients with advanced RCC. CABOSUN is being conducted by The Alliance for Clinical Trials in Oncology as part of Exelixis’ collaboration with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP). The final results from CABOSUN will be submitted for presentation at a future medical conference.

"The positive outcome of CABOSUN is extremely exciting, as it marks the very first time that a therapy has shown a progression-free survival benefit over standard of care first-line treatment sunitinib for patients with previously untreated advanced renal cell carcinoma," said Toni K. Choueiri, M.D., Clinical Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and chair of the CABOSUN study. "Based on these findings, cabozantinib may have the potential to become a new gold standard for previously untreated patients following their diagnosis with advanced kidney cancer."

"All of us at the Alliance for Clinical Trials in Oncology are very gratified to have successfully demonstrated the potential of first-line cabozantinib to benefit patients with renal cell carcinoma in the CABOSUN study. This trial exemplifies how NCI-sponsored studies can be efficient, accrue rapidly, and yield results highly relevant to the field," said Michael J. Morris, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center, and Chair of the Alliance Genitourinary (GU) Committee.

Exelixis will share the results of CABOSUN with regulatory authorities to discuss potential next steps in the development and submission strategy for cabozantinib as a treatment of first-line advanced renal cell carcinoma. Exelixis is also working closely with clinical advisors on the development plan for cabozantinib in future clinical trials in other genitourinary malignancies.

"Demonstrating an improvement in progression-free survival with cabozantinib compared to sunitinib as a first-line treatment represents an important milestone for patients with previously untreated RCC," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "We are thrilled to be a part of the many recent advances in the treatment of advanced kidney cancer and would like to thank the patients, physicians, nurses, caregivers, the Alliance cooperative group and NCI-CTEP who made this clinical trial possible. We look forward to pursuing next steps in the development of cabozantinib in the first-line treatment of patients with advanced RCC and other GU malignancies."

About the CABOSUN Study

CABOSUN is a randomized, open-label, active-controlled phase 2 trial that was designed to enroll 150 patients with advanced RCC determined to be intermediate- or poor-risk by the International Metastatic RCC Database Consortium (IMDC) criteria. Patients were randomized 1:1 to receive cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, 4 weeks on followed by 2 weeks off). The randomization was stratified by the IMDC risk strata (intermediate or poor risk) and presence of bone metastasis (yes, no). Enrollment was completed in March 2015. The primary endpoint was PFS, defined as time from randomization to disease progression or death, whichever occurs first. Positive PFS results have formed the basis for previous regulatory approvals of treatments in the first-line setting, including sunitinib. Secondary endpoints included overall survival and objective response rate. Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0-2, and had to be intermediate or poor risk, per the IMDC Criteria (Heng JCO 2009). Prior systemic treatment for RCC was not permitted. With 123 events (disease progression or death), the log-rank statistic has 85 percent power (with a one-sided type I error rate=0.12) to detect a hazard ratio of 0.67. Between July 9, 2013 and April 6, 2015, 157 patients were randomized: 79 patients on the cabozantinib arm and 78 patients on the sunitinib arm.

Please see Important Safety Information below and full U.S. prescribing information at View Source

About Advanced Renal Cell Carcinoma

The American Cancer Society’s 2016 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 Clear cell RCC is the most common type of kidney cancer in adults.2 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 12 percent, with no identified cure for the disease.1 Approximately 30,000 patients in the U.S. and 68,000 globally require treatment.3

The majority of clear cell RCC tumors have lower than normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL and VEGF.4,5 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.6-9 MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.5,6

About CABOMETYX

CABOMETYX targets include MET, AXL and VEGFR-1, -2 and -3. In preclinical models, cabozantinib has been shown to inhibit the activity of these receptors, which are involved in normal cellular function and pathologic processes such as tumor angiogenesis, invasiveness, metastasis and drug resistance.

CABOMETYX, the tablet formulation of cabozantinib, is available in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg orally, once daily.

On April 25, the FDA approved CABOMETYX tablets for the treatment of patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy.

On January 28, 2016, the European Medicines Agency (EMA) validated Exelixis’ Marketing Authorization Application (MAA) for cabozantinib as a treatment for patients with advanced renal cell carcinoma who have received one prior therapy. The MAA has been granted accelerated assessment, making it eligible for a 150-day review, versus the standard 210 days. On February 29, 2016, Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications outside of the United States, Canada and Japan.

Important Safety Information

Hemorrhage: Severe hemorrhage occurred with CABOMETYX. The incidence of Grade ≥3 hemorrhagic events was 2.1% in CABOMETYX-treated patients and 1.6% in everolimus-treated patients. Fatal hemorrhages also occurred in the cabozantinib clinical program. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.

Gastrointestinal (GI) Perforations and Fistulas: Fistulas were reported in 1.2% (including 0.6% anal fistula) of CABOMETYX-treated patients and 0% of everolimus-treated patients. GI perforations were reported in 0.9% of CABOMETYX-treated patients and 0.6% of everolimus-treated patients. Fatal perforations occurred in the cabozantinib clinical program. Monitor patients for symptoms of fistulas and perforations. Discontinue CABOMETYX in patients who experience a fistula that cannot be appropriately managed or a GI perforation.

Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. Venous thromboembolism was reported in 7.3% of CABOMETYX-treated patients and 2.5% of everolimus-treated patients. Pulmonary embolism occurred in 3.9% of CABOMETYX-treated patients and 0.3% of everolimus-treated patients. Events of arterial thromboembolism were reported in 0.9% of CABOMETYX-treated patients and 0.3% of everolimus-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.

Hypertension and Hypertensive Crisis: CABOMETYX treatment results in an increased incidence of treatment-emergent hypertension. Hypertension was reported in 37% (15% Grade ≥3) of CABOMETYX-treated patients and 7.1% (3.1% Grade ≥3) of everolimus-treated patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy. Discontinue CABOMETYX if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.

Diarrhea: Diarrhea occurred in 74% of patients treated with CABOMETYX and in 28% of patients treated with everolimus. Grade 3 diarrhea occurred in 11% of CABOMETYX-treated patients and in 2% of everolimus-treated patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose. Dose modification due to diarrhea occurred in 26% of patients.

Palmar-Plantar Erythrodysesthesia Syndrome (PPES): Palmar-plantar erythrodysesthesia syndrome (PPES) occurred in 42% of patients treated with CABOMETYX and in 6% of patients treated with everolimus. Grade 3 PPES occurred in 8.2% of CABOMETYX-treated patients and in <1% of everolimus-treated patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPES or Grade 3 PPES until improvement to Grade 1; resume CABOMETYX at a reduced dose. Dose modification due to PPES occurred in 16% of patients.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Embryo-fetal Toxicity: CABOMETYX can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the last dose.

Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, PPES, hypertension, vomiting, weight decreased, and constipation.

Drug Interactions: Strong CYP3A4 inhibitors and inducers: Reduce the dosage of CABOMETYX if concomitant use with strong CYP3A4 inhibitors cannot be avoided. Increase the dosage of CABOMETYX if concomitant use with strong CYP3A4 inducers cannot be avoided.

Lactation: Advise a lactating woman not to breastfeed during treatment with CABOMETYX and for 4 months after the final dose.

Reproductive Potential: Contraception―Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the final dose. Infertility ―CABOMETYX may impair fertility in females and males of reproductive potential.

Hepatic Impairment: Reduce the CABOMETYX dose in patients with mild (Child-Pugh score [C-P] A) or moderate (C-P B) hepatic impairment. CABOMETYX is not recommended for use in patients with severe hepatic impairment.

Please see full Prescribing Information at View Source

On May 23, 2016 Medivation, Inc. (NASDAQ: MDVN) reportedd that the talazoparib-containing arm of the I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2) has been activated (Press release, Medivation, MAY 23, 2016, View Source [SID:1234512693]). I-SPY 2, sponsored by the QuantumLeap Healthcare Collaborative, combines a personalized medicine approach and novel trial design to study investigational treatments in the neoadjuvant setting and is being conducted by a consortium consisting of the U.S. Food and Drug Administration (FDA), the National Cancer Institute (NCI), pharmaceutical and biotech companies, leading academic medical centers and patient advocates.

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"The I-SPY 2 TRIAL is designed to rapidly test promising agents to reduce the cost, time and number of patients needed to bring new therapies to breast cancer patients who urgently need new treatment options," said Laura J. Esserman, M.D., Principal Investigator of I-SPY 2 and Director of the Carol Franc Buck Breast Care Center at the UCSF Helen Diller Family Comprehensive Cancer Center. "We are very excited to initiate a new trial arm of talazoparib that is designed to optimize our understanding of this investigational drug and avoid some of the complications of paclitaxel, which is part of the current standard treatment. We are building on what we know of the PARP-inhibitor drug class and looking for ways to maximize benefit and minimize toxicity, which is what all women want."

The I-SPY 2 TRIAL is a Phase II, randomized, controlled, multi-center trial for women with newly diagnosed, locally advanced breast cancer (Stage II/III). The trial employs an adaptive design, matching experimental therapies with patients based on the use of biomarkers, investigating whether new therapies can be added to standard chemotherapy or whether they may replace certain components of standard chemotherapy in the neoadjuvant setting. Therapies that are found effective can move onto a more focused Phase III registration trial.

"We are delighted that the combination of talazoparib and irinotecan was chosen to be evaluated in this innovative trial design seeking to replace components of standard chemotherapy with more targeted, potentially less toxic agents," said Amy Peterson, M.D., Vice President, Clinical Research, Medivation. "This trial will allow us to gather important information about the activity and tolerability of this combination in a breast cancer patient population that goes beyond germline BRCA1/2 carriers and is an example of Medivation’s commitment to rapidly and efficiently bring impactful medicines to patients in need."

The talazoparib arm of the I-SPY 2 TRIAL will enroll up to 75 patients with HER-2 negative breast cancer. Patients will be treated initially with talazoparib daily and irinotecan every two weeks for 12 weeks followed by treatment with doxorubicin and cyclophosphamide. Patients in the comparator arm will receive standard paclitaxel therapy followed by doxorubicin and cyclophosphamide treatment. The primary endpoint of the trial is pathologic complete response (pCR), defined as the absence of clinical and pathological evidence of invasive tumor in breast or lymph nodes.

For more information about the I-SPY 2 TRIAL, visit www.clinicaltrials.gov, trial identifier NCT01042379.

About Talazoparib

Talazoparib is a potent and specific inhibitor of PARP 1 and 2(i) that is being developed by Medivation for the treatment of selected solid tumors. In pre-clinical studies, talazoparib has shown single-agent anti-tumor activity, as well as synergy in combination with lowered doses of DNA-damaging agents, due to its dual mechanisms of cytotoxicity, PARP trapping, and inhibition of PARP enzyme activity. Trapping of PARP on DNA impairs DNA replication resulting in tumor cell death. Talazoparib currently is in Phase III development for patients with locally advanced and/or metastatic breast cancer who harbor a germline BRCA1/2 mutation.

On May 23, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported that the European Commission (EC) has granted a conditional marketing authorization for first-in-class CD38 antibody DARZALEX (daratumumab) (Press release, Genmab, MAY 23, 2016, View Source [SID:1234512691]).

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The conditional approval is for the use of DARZALEX as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor (PI) and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. The EC approval follows a positive opinion issued for DARZALEX by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in April 2016. Conditional marketing authorizations are granted by the EMA for medicines where the benefit of immediate availability outweighs the risk of less comprehensive data than normally required. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

DARZALEX is the first human CD38 monoclonal antibody (mAb) approved in Europe. The European approval follows the November 2015 U.S. Food and Drug Administration (FDA) approval of DARZALEX for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize DARZALEX.

The marketing authorization was based on data from the Phase II study (SIRIUS MMY2002, published in The Lancet in January 2016), the Phase I/II GEN501 monotherapy study (published in The New England Journal of Medicine in August 2015) and data from three additional supportive studies. These studies included heavily pre-treated patients with relapsed and refractory multiple myeloma who had exhausted other approved treatment options and whose disease was progressive at enrolment. Findings from a combined efficacy analysis of the GEN501 and MMY2002 (SIRIUS) trials demonstrated that after a mean follow-up of 14.8 months, the estimated median overall survival (OS) for single-agent daratumumab (16 mg/kg) in these heavily pre-treated patients was 20 months (95 percent Confidence Interval, 15 months to not yet estimable). The overall response rate (ORR) for the combined analysis was 31 percent, and 83 percent of patients achieved stable disease or better.1

"At Genmab we are driven by a desire to improve the quality of life for cancer patients and their families. The approval of the marketing application for DARZALEX provides the opportunity to do just that for multiple myeloma patients living in the EU and represents a landmark event for these patients and their families, as well as for Genmab and Janssen," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

Daratumumab demonstrated a clinically manageable safety profile. The most commonly occurring adverse reactions (in 20 percent or more of patients in three pooled clinical studies) were infusion-related reactions (IRRs), fatigue, pyrexia, cough, nausea, back pain, upper respiratory tract infection, anemia, neutropenia (abnormally low levels of neutrophils, a type of white blood cell) and thrombocytopenia (abnormally low levels of platelets in the blood).2
In data from three pooled clinical studies including a total of 156 patients, four percent of patients discontinued treatment due to adverse reactions, none of which were considered drug-related. IRRs were reported in approximately half of all patients treated with DARZALEX, the majority of which (91 percent) occurred during the first infusion. Seven percent of patients had an IRR at more than one infusion. Common (≥5 percent) symptoms of IRRs included nasal congestion, chills, cough, allergic rhinitis, throat irritation, dyspnea, and nausea, and these were mild to moderate in severity.2 Severe IRRs (4 percent), including bronchospasm (1.3 percent), hypertension (1.3 percent), and hypoxia, or decreased oxygen supply to the tissues (0.6 percent), were also reported.2

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.3 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.4 Approximately 26,850 new patients were estimated to be diagnosed with multiple myeloma and approximately 11,240 people would die from the disease in the U.S. in 2015.5 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would die from the disease in 2015.6 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.7 Patients who relapse after treatment with standard therapies, including proteasome inhibitors or immunomodulatory agents, have poor prognoses and few treatment options.8

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.2 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It is believed to induce rapid tumor cell death through programmed cell death, or apoptosis,2,9 and multiple immune-mediated mechanisms, including complement-dependent cytotoxicity,2,9 antibody-dependent cellular phagocytosis10,11 and antibody-dependent cellular cytotoxicity.2,9 In addition, daratumumab therapy results in a reduction of immune-suppressive myeloid derived suppressor cells (MDSCs) and subsets of regulatory T cells (Tregs) and B cells (Bregs), all of which express CD38. These reductions in MDSCs, Tregs and Bregs were accompanied by increases in CD4+ and CD8+ T cell numbers in both the peripheral blood and bone marrow.2

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma, non-Hodgkin’s lymphoma and a solid tumor.

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, Chugai, MAY 23, 2016, View Source [SID:1234512672]).

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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.

* T. Sobue, et al., Cancer White Paper 2012, Shinoharashinsha Inc.

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 non-small 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.

On May 23, 2016 Astellas Pharma Inc. (President and CEO: Yoshihiko Hatanaka; Headquarters: Tokyo; TSE: 4503; "Astellas"), Daiichi Sankyo Company, Limited (President and CEO: Joji Nakayama; Headquarters: Tokyo; TSE: 4568; "Daiichi Sankyo"), and Takeda Pharmaceutical Company Limited (President and CEO: Christophe Weber; Headquarters: Osaka; TSE: 4502; "Takeda") reported that they have entered into a joint research agreement (Press release, Astellas, MAY 23, 2016, http://www.astellas.com/en/corporate/news/detail/astellas-daiichi-sankyo-and-ta.html [SID:1234512671]). It is an agreement to comprehensively acquire and analyze fundamental biomarker*1 data on healthy adult volunteers in order to optimize and accelerate the development of innovative medicines.

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Biomarkers are used in patient stratification, investigation of a drug’s mechanism of action, and efficacy and safety indices, and are utilized in a wide variety of scenarios, ranging from the exploration stage of drug candidacy to clinical studies and daily diagnostics. However, fundamental biomarker data from healthy adults, which can be used for comparing and contrasting with patients in the preclinical and clinical stages, has not been sufficiently accumulated globally, and further enhancement of data construction is expected.

Based on this agreement, Astellas, Daiichi Sankyo, and Takeda will comprehensively acquire fundamental data from healthy adult volunteers that is required for clinical studies using protein and metabolite biomarkers, and undertake joint analysis thereon. Samples will be acquired at a clinical research organization associated with Leiden University in the Netherlands and be under the supervision of Dr. Thomas Hankemeier, Professor at Leiden University. The analysis results will be mainly utilized in the companies’ therapeutic areas of focus*2. Data gained from this analysis will be publicized so that it may be widely utilized in various types of drug discovery research to meet patients’ unmet needs.

Astellas, Daiichi Sankyo, and Takeda aim to contribute to the enhancement of health and welfare of people around the world through creating innovative medicine. Through this joint research, it will become possible to establish a base of comprehensive biomarker data— something that is difficult for individual pharmaceutical companies to do— as well as lead to more effective drug discovery by using a translational research*3 approach. The three companies will contribute to the optimization and acceleration of innovation in Japan-originated drug discovery through this collaboration as pharmaceutical companies with research bases in Japan.