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BioInvent receives €2 million milestone payment from Daiichi Sankyo for licensed n-CoDeR® antibody progressing into Phase I clinical trial

On February 29, 2016 BioInvent International (BINV) reported that it will receive a €2 million milestone payment under the collaboration with Daiichi Sankyo pertaining to the progression of an anti-FGFR4 antibody into a Phase I clinical trial in the EU (Press release, BioInvent, FEB 29, 2016, http://www.bioinvent.com/media-centre/press-releases/release/?ReleaseID=0343D46385679286 [SID:1234509259]).

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The anti-FGFR4 antibody, known as U3-1784, was discovered by Daiichi Sankyo utilizing BioInvent’s n-CoDeR phage display library. Its target indication is for solid cancer tumors.

Under the terms of BioInvent’s licensing agreement with Daiichi Sankyo, payments are due to BioInvent when certain clinical milestones are achieved and royalty payments are due when a product is sold on the market. Beginning a Phase I clinical trial is a milestone that triggers a payment to BioInvent.

"We are very pleased that our partner Daiichi Sankyo has progressed U3-1784 into a Phase I clinical trial", said Michael Oredsson, CEO of BioInvent. "It is yet another example of an n-CoDeR library derived antibody that is being successfully developed through to the clinic by a leading global pharmaceutical company. We wish Daiichi Sankyo continued success with this antibody in their clinical program."

EISAI’S ANTICANCER AGENT HALAVEN(R) NEWLY APPROVED IN JAPAN FOR TREATMENT OF SOFT TISSUE SARCOMA

On February 29, 2016 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that it has received approval in Japan for its in-house developed anticancer agent Halaven (eribulin mesylate) as a treatment of patients with soft tissue sarcoma (Press release, Eisai, FEB 29, 2016, View Source [SID:1234509258]).

Halaven is the first and only single agent to demonstrate an overall survival (OS) benefit in a Phase III trial in patients with advanced, recurrent or metastatic soft tissue sarcoma (liposarcoma or leiomyosarcoma). Following approval for use in the treatment of inoperable or recurrent breast cancer in Japan, this marks the second indication for which Halaven has been approved based on a statistically significant extension of OS.

In a Phase III clinical study (Study 309) in patients with locally advanced, locally recurrent or metastatic soft tissue sarcoma (liposarcoma or leiomyosarcoma) who had disease progression following standard therapies which must have included an anthracycline and at least one other additional regimen, Halaven demonstrated a statistically significant extension in the study’s primary endpoint of OS over the comparator treatment dacarbazine. 1 The most common adverse reactions (incidence greater than or equal to 25%) in patients treated with Halaven in the study were neutropenia, fatigue, alopecia, nausea, and peripheral neuropathy, which was consistent with the known side-effect profile of Halaven. Furthermore, in a Phase II clinical study (Study 217) of Halaven in patients with advanced or recurrent soft tissue sarcoma who had received chemotherapy conducted within Japan, the results also suggested clinical efficacy for Halaven.2

Soft tissue sarcoma is a collective term for a diverse group of malignant tumors that occur throughout the soft tissues (including fat, muscle, nerves, fibrous tissues and blood vessels) in the body. According to a patient survey conducted by Japan’s Ministry of Health, Labour and Welfare, there are approximately 4,000 patients with soft tissue sarcoma in Japan.
In January 2016, Halaven was approved in the United States as a treatment of patients with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen, and applications seeking approval for use in the treatment of soft tissue sarcoma are currently under review in the EU, Switzerland, Russia, Australia, and Brazil. Halaven has been designated as an orphan drug for the treatment of soft tissue sarcoma in the United States and Japan.

Halaven is a halichondrin class microtubule dynamics inhibitor with a distinct binding profile. Recent non-clinical studies showed that Halaven is associated with increased vascular perfusion and permeability in tumor cores.3 Halaven promotes the epithelial state and decreases the capacity of breast cancer cells to migrate. 4 Halaven is currently approved for use in the treatment of breast cancer in approximately 60 countries including Japan and countries in Europe, the Americas and Asia.
Through obtaining this additional approval, Eisai aims to enhance the clinical value of Halaven to contribute further toward addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.

[Notes to editors]
1. Product Outline (New Information Related to Additional Indication Underlined) 1) Product name Halaven Injection 1 mg 2) Generic name Eribulin mesylate 3) Indication for use Inoperable or recurrent breast cancer, soft tissue sarcoma 4) Dosage and administration The usual adult dose of eribulin mesylate is 1.4 mg/m2 body surface area, administered intravenously as a single dose over 2 to 5 minutes, once a week. Treatment should be continued for 2 consecutive weeks, followed by a third week of drug cessation. With each cycle lasting 3 weeks, the treatment should be repeated. The dose may be reduced, depending on the condition of the individual patient.

2. About Halaven
Halaven is the first in the halichondrin class of microtubule dynamics inhibitors with a novel mechanism of action. Structurally Halaven is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Halaven is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division. In addition, recent non-clinical studies showed that Halaven is associated with increased vascular perfusion and permeability in tumor cores.3 Halaven promotes the epithelial state and decreases the capacity of breast cancer cells to migrate.4

Halaven was first approved in November 2010 in the United States as a treatment for patients with metastatic breast cancer who have received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting. Halaven is currently approved for use in the treatment of breast cancer in approximately 60 countries worldwide, including Japan and countries in the Europe, Americas and Asia. In Japan, Halaven has been approved to treat inoperable or recurrent breast cancer and was launched in the country in July 2011. Halaven has also been approved in countries in Europe and Asia indicated as a treatment for patients with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments.

Regarding soft tissue sarcoma, Halaven was approved in the United States for the treatment of patients with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen in January 2016, and was approved in Japan for the treatment of soft tissue sarcoma in February 2016. Applications seeking approval for use in the treatment of soft tissue sarcoma are currently under review in the EU, Switzerland, Russia, Australia, and Brazil. Furthermore, Halaven has been designated as an orphan drug for soft-tissue sarcoma in the United States and Japan.

3. About Soft Tissue Sarcoma
Soft tissue sarcoma is a collective term for a diverse group of malignant tumors that occur throughout the soft tissue (including fat, muscle, nerves, fibrous tissues and blood vessels) in the body. Approximately 12,000 patients in the United States and 29,000 patients in Europe are diagnosed with soft tissue sarcoma each year. According to a patient survey conducted by Japan’s Ministry of Health, Labour and Welfare, there are approximately 4,000 patients with soft tissue sarcoma in Japan. As the structures where the tumors originate are diverse, there are various types of soft tissue sarcoma, and the most common types include leiomyosarcoma, liposarcoma and malignant fibrous histiocytoma. While treatment of soft tissue sarcoma is focused on curative surgery, if the degree of malignancy is high, treatment then becomes a combination of chemotherapy and radiation therapy. As outcomes are poor for patients with advanced disease, it remains a disease with significant unmet medical need.

4. About Study 3091
Conducted primarily in Europe and the United States, Study 309 was a multicenter, open-label, randomized Phase III study comparing the efficacy and safety of Halaven ("eribulin") versus dacarbazine in 452 patients (aged 18 or over) with locally advanced, locally recurrent or metastatic soft tissue sarcoma (liposarcoma or leiomyosarcoma) who had disease progression following standard therapies which must have included an anthracycline and at least one other additional regimen. Patients received either eribulin (1.4 mg/m2 administered intravenously on Day 1 and Day 8) or dacarbazine (850–1200 mg/m2 administered intravenously on Day 1) every 21 days until disease progression. From the results for the study, eribulin demonstrated a statistically significant extension in the study’s primary endpoint of overall survival (OS) over the comparator treatment dacarbazine (eribulin median OS: 13.5 months vs dacarbazine median OS: 11.5 months; Hazard Ratio 0.77 [95% CI=0.62-0.95], p=0.0169). Furthermore, in the study’s secondary endpoints, there was no statistically significant difference found between eribulin and dacarbazine in either progression-free survival (PFS) (median PFS: 2.6 months in both arms) or progression-free rate at 12 weeks (PFR12wks) (eribulin PFR12wks: 33% vs dacarbazine PFR12wks: 29%). The most common adverse reactions (incidence greater than or equal to 25%) in study patients with liposarcoma or leiomyosarcoma treated with eribulin were neutropenia, fatigue, alopecia, nausea, and peripheral neuropathy, which was consistent with the known side-effect profile of eribulin.

5. About Study 217 (Results Presented at 50th Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)) 2
Conducted in Japan, Study 217 was an open label, multicenter, Phase II study to evaluate the efficacy and safety of eribulin in 51 previously treated subjects with advanced or recurrent soft tissue sarcoma. Patients in the study received eribulin (1.4 mg/m2 administered intravenously on Day 1 and Day 8) every 21 days until disease progression, and the primary endpoint was PFR12wks. The results of the study demonstrated efficacy for eribulin in previously treated patients with advanced soft tissue sarcoma. PFR12wks in all evaluated groups of soft tissue sarcoma was 51.0%. Furthermore, the PFR12wks in patients with liposarcoma or leiomyosarcoma (35 patients) and in patients with other types of soft tissue sarcoma (16 patients) were 60.0% and 31.3%, respectively. The most common treatment emergent adverse events of Grade 3 or higher (Common Terminology Criteria for Adverse Events) were neutropenia (86.3%), white blood cell decrease (74.5%), lymphocyte decrease (31.4%), anemia (11.8%) and febrile neutropenia (7.8%).

European Committee for Medicinal Products for Human Use recommends approval of Giotrif® (afatinib) for advanced squamous cell cancer of the lung

On February 29, 2016 Boehringer Ingelheim reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion for the approval of Giotrif (afatinib) for the treatment of patients with advanced squamous cell carcinoma (SqCC) of the lung whose disease has progressed on or after treatment with platinum-based chemotherapy (Press release, Boehringer Ingelheim, FEB 29, 2016, View Source [SID:1234509257]).

Afatinib is already approved for the treatment of patients with EGFR mutated non-small cell lung cancer (NSCLC).*

The CHMP positive opinion is based on the results of the head-to-head LUX-Lung 8 trial in patients with SqCC of the lung whose tumours progressed on or after first-line chemotherapy. Afatinib, compared to erlotinib, demonstrated:1

Significant delay in progression of lung cancer (PFS, progression-free survival, primary endpoint), reducing the risk of cancer progression by 19%
Significant improvement in overall survival (OS, key secondary endpoint), reducing the risk of death by 19%
An improvement in quality of life and control of cancer symptoms
The rate of severe adverse events was similar between the two treatment arms with differences observed in the incidence of certain side effects: a higher incidence of severe diarrhoea and stomatitis (mouth sores) was observed with afatinib compared to erlotinib (grade 3 diarrhoea: 10% vs 2%; grade 3 stomatitis: 4% vs 0%), while a higher incidence of severe rash/acne was reported with erlotinib compared to afatinib (grade 3 rash/acne: 10% vs 6%).1
SqCC of the lung develops in the cells lining the airways and represents approximately 20-30% of NSCLC cases.2,3 It is associated with a poor prognosis, limited survival and symptoms like cough and dyspnoea; the median OS after diagnosis of advanced SqCC is around one year.4,5

Dr. Mehdi Shahidi, Medical Head, Solid Tumour Oncology, Boehringer Ingelheim commented: "Despite recent advances in the treatment of squamous cell lung cancer, this disease remains challenging to treat. We are pleased to receive this positive opinion from the CHMP for afatinib; not only does it represent the potential availability of the first oral treatment option specifically approved for patients with squamous cell lung cancer, it also confirms the positive profile of afatinib, a second-generation EGFR targeting agent, when compared to a first-generation agent."

LUX-Lung 8 is part of the afatinib LUX-Lung programme – the largest collection of clinical trials of any EGFR tyrosine kinase inhibitor (TKI), with over 3760 patients across eight studies conducted across the world. The comprehensive programme includes two pivotal studies in the first-line setting, LUX-Lung 3 and 6, as well as two head-to-head studies (LUX-Lung 7 and 8) of afatinib versus first-generation EGFR TKIs. The LUX-Lung programme has involved lung cancer specialists across over 680 sites in 40 countries around the world, reflecting the strong partnership between Boehringer Ingelheim and the lung cancer specialist community.

Afatinib is already approved in over 60 countries for the first-line treatment of EGFR mutation-positive NSCLC*, and recent results from the LUX-Lung 7 trial positively underscored benefits of afatinib versus another first-generation EGFR targeting agent in this indication.6 Results of this global Phase IIb head-to-head trial demonstrated afatinib was superior in reducing the risk of lung cancer progression and the risk of treatment failure both by 27% compared to gefitinib.6

For more information about the LUX-Lung 8 Trial, please see Professor Jean-Charles Soria’s publication in The Lancet Oncology

Two Quality of Life (QoL) Interim Analyses Presented at ASCO Quality Care Symposium Represent First Results from ABOUND ABRAXANE® Lung Cancer Program

On February 27,2016 Celgene Corporation (NASDAQ:CELG) reported that two interim analyses of exploratory quality of life (QoL) endpoints in the ongoing phase III ABOUND.sqm clinical study investigating ABRAXANE (paclitaxel protein-bound particles for injectable suspension)(albumin-bound) in patients with advanced, squamous non-small cell lung cancer (NSCLC) were presented at the 2016 ASCO (Free ASCO Whitepaper) Quality Care Symposium (Press release, Celgene, FEB 27, 2016, View Source [SID:1234509247]).

In the ABOUND.sqm study, patients received four 21-day cycles of ABRAXANE (100 mg/m2 on days 1, 8 and 15) plus carboplatin (AUC6 on day 1) and those with a response or stable disease could be randomized to receive either ABRAXANE (100 mg/m2 on days 1, 8) plus best supportive care or best supportive care alone in 21-day cycles until disease progression.

The analyses included 159 patients from the study who were evaluable for radiological response and QoL. In the two analyses 99% of patients had an ECOG performance status of 0-1 and pre-defined QoL measures including the LCSS (Global Score, Average Total Score, 3-Item Index, Average Symptom Burden Index and Lung Cancer Symptoms) and EuroQol EQ-5D-5L assessment were taken on day one of each cycle during the initial treatment phase.

The first analysis evaluated the therapeutic impact of chemotherapy on patient symptoms and activities. For all patients in the analysis, quality of life as measured by the LCSS and EuroQoL (EQ-5D-5L) was generally either maintained or improved throughout the entire treatment course.

The second analysis assessed the impact of radiological response on Quality of Life. In this analysis, 93/159 patients had an unconfirmed radiological response and 66/159 did not. Responders had a greater improvement in lung cancer symptom score, as measured by the LCSS and EQ-5D-5L scores.

Importantly, among patients who reported problems with mobility, self care, usual activities of living, pain/discomfort, or anxiety/depression prior to treatment, 38 – 47% reported complete resolution of these problems at least once during treatment. This was more pronounced in patients who achieved a radiological response, with complete resolution at least once reported in 42 – 59% of patients.

"Inclusion of quality of life measures is particularly important when so few prospective trials in advanced non-small cell lung cancer currently include such analyses," said Dr. Corey Langer of the University of Pennsylvania and lead investigator of one of the analyses. "These data demonstrate a correlation between radiologic response and patient reported quality of life."

Indication

ABRAXANE is indicated for the first-line treatment of locally advanced or metastatic non-small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.

Important Safety Information

WARNING – NEUTROPENIA

Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE

Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS
CONTRAINDICATIONS

Neutrophil Counts

ABRAXANE should not be used in patients who have baseline neutrophil counts of < 1500cells/mm3
Hypersensitivity

Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug
WARNINGS AND PRECAUTIONS

Hematologic Effects

Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity of ABRAXANE. In a clinical study, Grade 3-4 neutropenia occurred in 47% of patients with non-small cell lung cancer (NSCLC)

Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15

Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1500 cells/mm3

In the case of severe neutropenia ( < 500 cells/mm3 for 7 days or more) during a course of ABRAXANE therapy, reduce the dose of ABRAXANE in subsequent courses in patients with NSCLC

Resume treatment if recommended at permanently reduced doses for both weekly ABRAXANE and every-3-week carboplatin after ANC recovers to at least 1500 cells/mm3 and platelet count of at least 100,000 cells/mm3 on Day 1 or to an ANC of at least 500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Days 8 or 15 of the cycle

Nervous System

Sensory neuropathy is dose- and schedule-dependent

The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification

If ≥ Grade 3 sensory neuropathy develops, withhold ABRAXANE treatment until resolution to ≤ Grade 1 followed by a dose reduction for all subsequent courses of ABRAXANE

Hypersensitivity

Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported

Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug

Hepatic Impairment

Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, administration of ABRAXANE in patients with hepatic impairment should be performed with caution

Patients with hepatic impairment may be at an increased risk of toxicity, particularly from myelosuppression, and should be monitored for development of profound myelosuppression

For NSCLC, the starting dose should be reduced for patients with moderate or severe hepatic impairment

Albumin (Human)

ABRAXANE contains albumin (human), a derivative of human blood

Use in Pregnancy: Pregnancy Category D

ABRAXANE can cause fetal harm when administered to a pregnant woman

If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus

Women of childbearing potential should be advised to avoid becoming pregnant while receiving ABRAXANE

Use in Men

Men should be advised not to father a child while receiving ABRAXANE

ADVERSE REACTIONS

Non-Small Cell Lung Cancer (NSCLC) Study

The most common adverse reactions (≥20%) of ABRAXANE in combination with carboplatin are anemia, neutropenia, thrombocytopenia, alopecia, peripheral neuropathy, nausea, and fatigue

The most common serious adverse reactions of ABRAXANE in combination with carboplatin for NSCLC are anemia (4%) and pneumonia (3%)

The most common adverse reactions resulting in permanent discontinuation of ABRAXANE are neutropenia (3%), thrombocytopenia (3%), and peripheral neuropathy (1%)

The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (24%), thrombocytopenia (13%), and anemia (6%)

The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (41%), thrombocytopenia (30%), and anemia (16%)

The following common (≥10% incidence) adverse reactions were observed at a similar incidence in ABRAXANE plus carboplatin-treated and paclitaxel injection plus carboplatin-treated patients: alopecia (56%), nausea (27%), fatigue (25%), decreased appetite (17%), asthenia (16%), constipation (16%), diarrhea (15%), vomiting (12%), dyspnea (12%), and rash (10%); incidence rates are for the ABRAXANE plus carboplatin treatment group

Adverse reactions with a difference of ≥2%, Grade 3 or higher, with combination use of ABRAXANE and carboplatin vs combination use of paclitaxel injection and carboplatin in NSCLC are anemia (28%, 7%), neutropenia (47%, 58%), thrombocytopenia (18%, 9%), and peripheral neuropathy (3%, 12%), respectively

Adverse reactions with a difference of ≥5%, Grades 1-4, with combination use of ABRAXANE and carboplatin vs combination use of paclitaxel injection and carboplatin in NSCLC are anemia (98%, 91%), thrombocytopenia (68%, 55%), peripheral neuropathy (48%, 64%), edema peripheral (10%, 4%), epistaxis (7%, 2%), arthralgia (13%, 25%), and myalgia (10%, 19%), respectively

Neutropenia (all grades) was reported in 85% of patients who received ABRAXANE and carboplatin vs 83% of patients who received paclitaxel injection and carboplatin

Postmarketing Experience With ABRAXANE and Other Paclitaxel Formulations

Severe and sometimes fatal hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied

There have been reports of congestive heart failure, left ventricular dysfunction, and atrioventricular block with ABRAXANE, primarily among individuals with underlying cardiac history or prior exposure to cardiotoxic drugs

There have been reports of extravasation of ABRAXANE. Given the possibility of extravasation, it is advisable to monitor closely the ABRAXANE infusion site for possible infiltration during drug administration

DRUG INTERACTIONS

Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4

USE IN SPECIFIC POPULATIONS

Nursing Mothers

It is not known whether paclitaxel is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother

Pediatric

The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated

Geriatric

Myelosuppression, peripheral neuropathy, and arthralgia were more frequent in patients ≥65 years of age treated with ABRAXANE and carboplatin in NSCLC

Renal Impairment

There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance < 30 mL/min)

DOSAGE AND ADMINISTRATION

Do not administer ABRAXANE to any patient with total bilirubin greater than 5 x ULN or AST greater than 10 x ULN

Reduce starting dose in NSCLC patients with moderate to severe hepatic impairment

Dose reductions or discontinuation may be needed based on severe hematologic or neurologic toxicity

Monitor patients closely

Please see full Prescribing Information, including Boxed WARNING.

20-F – Annual and transition report of foreign private issuers [Sections 13 or 15(d)]

Qiagen has filed a 20-F – Annual and transition report of foreign private issuers [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 20-F, QIAGEN, FEB 26, 2016, View Source [SID1234509325]).