On July 30, 2015 Juno Therapeutics, Inc. (Nasdaq:JUNO), a biopharmaceutical company focused on re-engaging the body’s immune system to revolutionize the treatment of cancer, reported the U.S. Food and Drug Administration (FDA) cleared the Company’s investigational new drug (IND) application for JCAR015 for treatment of adult patients with relapsed/refractory acute lymphoblastic leukemia (r/r ALL) (Press release, Juno, JUL 30, 2015, View Source [SID:1234506765]).

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The IND enables Juno to initiate a multi-center, pivotal Phase 2 trial evaluating JCAR015 in patients with r/r ALL. The trial is scheduled to begin in the near term, with the potential to file for registration by late 2016 or early 2017. JCAR015, Juno’s most advanced product candidate, is an autologous chimeric antigen receptor (CAR) T cell immunotherapy targeting CD19, a protein expressed on the surface of most B cell leukemias and lymphomas.

"Based on the encouraging results of JCAR015 in its Phase 1 adult ALL trial conducted by Memorial Sloan Kettering Cancer Center, we are excited to begin Juno’s first pivotal trial investigating this product candidate in a multi-center study," said Mark Frohlich, M.D., Juno EVP of development and portfolio strategy. "FDA clearance of the JCAR015 IND for this pivotal Phase 2 trial is a significant milestone for the company, highlighting the early returns on the investments we have made in process development and manufacturing as well as providing clarity on a potential path toward our first product approval."

The initial trial to be conducted under this IND is titled "Protocol 015001: A Phase 2, single-arm, Multicenter Trial to Determine the Efficacy and Safety of JCAR015 in Adult Subjects with Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia (The ROCKET Study)." The primary objective of this trial is to evaluate the efficacy of JCAR015 as measured by overall remission rate in subjects with morphologic evidence of disease (5% or more leukemic blasts in the bone marrow). The trial will also evaluate the safety and tolerability of the therapy. The study will open at 14 clinical sites in the U.S. and enroll approximately 90 subjects in order to achieve 50 subjects with morphologic disease following salvage chemotherapy.

About Juno’s Chimeric Antigen Receptor (CAR) and T Cell Receptor (TCR) Technologies
Juno’s chimeric antigen receptor (CAR) and T cell receptor technologies (TCR) genetically engineer T cells to recognize and kill cancer cells. Juno’s CAR T cell technology inserts a gene for a particular CAR into the T cell, enabling it to recognize cancer cells based on the expression of a specific protein located on the cells surface. Juno’s TCR technology provides the T cells with a specific T cell receptor to recognize protein fragments derived from either the surface or inside the cell. When either type of engineered T cell engages the target protein on the cancer cell, it initiates a cell-killing response against the cancer cell.

On July 30, 2015 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported it has entered into a global license and supply agreement with Sanofi to utilize Captisol in the development and commercialization of SAR-125844, a potent MET kinase inhibitor (Press release, Ligand, JUL 30, 2015, View Source [SID:1234506760]).

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Under the terms of the license, Ligand will be eligible to receive potential milestone payments, royalties on future net sales and revenue from Captisol material sales. Sanofi will be responsible for all costs related to the program.

"This represents the progression and expansion of our relationship with Sanofi as they continue to make progress on SAR-125844, a novel, selective MET kinase inhibitor," commented John Higgins, President and Chief Executive Officer of Ligand. "Captisol continues to bring significant value to our partners’ programs and shows great promise in enabling compounds in oncology, CNS, anti-infectives and many other therapy areas."

About Captisol

Captisol is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. Captisol was invented and initially developed by scientists in the laboratories of Dr. Valentino Stella at the University of Kansas’ Higuchi Biosciences Center for specific use in drug development and formulation. This unique technology has enabled seven FDA-approved products, including Amgen’s Kyprolis, Baxter International’s Nexterone and Merck’s NOXAFIL IV. There are more than 30 Captisol-enabled products currently in clinical development.

About SAR-125844

SAR-125844 is a potent, selective and reversible ATP-competitive MET tyrosine kinase inhibitor for intravenous (IV) administration. SAR-125844 recently completed a first-in-human, open-label, non-randomized, single agent, Phase 1 study in advanced/refractory solid tumor patients.

On July 30, 2015 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, and Jiangsu Hengrui Medicine Co., Ltd., a fully integrated pharmaceutical company based in China, reported an exclusive license agreement for the development, registration, manufacture, and commercialization of rolapitant in China (Press release, TESARO, JUL 30, 2015, View Source [SID:1234506756]).

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Hengrui will make upfront and milestone payments to TESARO subject to the achievement of certain events, in addition to royalty payments on annual net sales in China. Additional financial details were not disclosed.

"TESARO is committed to advancing new therapeutic options for patients with cancer, and we are pleased to be working with Hengrui to develop and commercialize rolapitant for patients in China," said Lonnie Moulder, CEO of TESARO. "Hengrui is a leading innovative pharmaceutical company in China, with a substantial portfolio of marketed oncology products, deep regulatory expertise, and a robust pipeline of product candidates. With a strong commitment to quality and a significant level of expertise in clinical development, regulatory affairs, and commercialization, we believe Hengrui is the optimal partner to develop rolapitant in China."

Piaoyang Sun, Chairman of the Board of Hengrui, added, "As one of the leading pharmaceutical companies in China, Hengrui has a rich history of delivering high quality oncology products worldwide and continues to be committed to developing innovative oncology medicines. In recent years, Hengrui has expanded its oncology portfolio to include cancer supportive care products, and the development and commercialization of rolapitant for China is the most recent example of our effort to make new therapeutic options available to millions of cancer patients here. We are extremely pleased to be working with TESARO, an emerging leader in the development of oncology specialty medicines."

Rolapitant is an investigational neurokinin-1 (NK-1) receptor antagonist being developed for the prevention of chemotherapy-induced nausea and vomiting (CINV). The New Drug Application (NDA) for oral rolapitant is currently under review by the U.S. Food and Drug Administration, with a PDUFA goal date of September 5, 2015. Rolapitant has not been approved by any regulatory agency.

On July 30, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported it has submitted the cobas EGFR Mutation Test v2 for Premarket Approval (PMA) to the U.S. Food and Drug Administration (FDA), as a companion diagnostic test for AZD9291, an AstraZeneca investigational therapy for non-small cell lung cancer patients with an acquired resistant mutation (Press release, Hoffmann-La Roche , JUL 30, 2015, View Source [SID:1234506754]).

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Patients with non-small cell lung cancer who have adenocarcinoma with tumor containing an EGFR sensitizing mutation show significant benefit from currently available EGFR TKI therapies. However, approximately two-thirds of these patients will relapse and develop drug resistance. In many cases, this resistance is caused by an acquired mutation called T790M. The cobas EGFR v2 test can aid clinicians to appropriately select NSCLC patients who have acquired the T790M mutation and are most likely to benefit from AstraZeneca’s novel therapy.

"The collaboration with AstraZeneca to be the companion diagnostic for their third generation EGFR drug therapy is a testament to the innovation and quality of Roche oncology assays and demonstrates the value of molecular testing in patients," said Paul Brown, Head of Roche Molecular Diagnostics (RMD). "At Roche Molecular Diagnostics, we have one of the broadest portfolios of FDA-approved tests for Oncology that enable clinicians to make informed treatment decisions for their patients."

"At AstraZeneca, we are focused on developing novel treatments that address the genetic drivers underlying lung cancer disease progression and resistance mechanisms. AZD9291 was designed to inhibit both the activating sensitising EGFRm and the resistance mutation, T790M. The partnership with Roche on developing a companion diagnostics test for AZD9291, ensures that physicians will be able to identify the patients most likely to benefit from the treatment," said Antoine Yver, Head of Oncology, Global Medicines Development at AstraZeneca.

About the cobas EGFR Mutation Test v2
The cobas EGFR Mutation Test v2 is built upon the existing FDA-approved cobas EGFR Mutation Test, developed by Roche. It is intended to identify a broad spectrum of EGFR mutations for patients with non-small cell lung cancer, including the T790M acquired resistant mutation.

About AZD9291
AZD9291 is a once daily, selective, irreversible EGFR TKI designed to target both the activating sensitising mutation, EGFRm, and T790M, the genetic mutation responsible for EGFR TKI treatment resistance in up to approximately two-thirds of cases of EGFRm advanced NSCLC. AZD9291 has been granted Breakthrough Therapy designation, Orphan Drug and Fast Track status by the US Food and Drug Administration (FDA).

On July 30, 2015 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that it has submitted applications to regulatory authorities in Japan, the United States and Europe (MHLW, FDA and EMA respectively) seeking an additional indication for its in-house developed anticancer agent Halaven (eribulin mesylate) as a treatment for soft tissue sarcoma (Press release, Eisai, JUL 30, 2015, View Source [SID:1234506753]).

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Halaven is the first and only single agent systemic therapy to demonstrate an improvement in overall survival (OS) in people previously treated for soft tissue sarcomas in a randomized controlled trial to date. In a Phase III clinical study (Study 309) which examined the efficacy and safety of Halaven versus dacarbazine in patients with locally advanced or recurrent and metastatic soft tissue sarcoma (one of two subtypes: leiomyosarcoma or adipocytic sarcoma) who had disease progression following standard therapies (including 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 (Halaven median OS: 13.5 months vs dacarbazine median OS: 11.5 months, Hazard Ratio (HR) 0.768 [95% CI=0.618-0.954], p=0.017). In this study, the most common treatment-emergent adverse events observed in the Halaven arm were fatigue or asthenia, neutropenia, nausea, alopecia, and peripheral neuropathy, which was consistent with the known side-effect profile of Halaven.
These data were presented at an oral session at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in June 20151.

Soft tissue sarcoma is a collective term for a diverse group of malignant tumors that occur throughout the soft tissue (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 the MHLW, there are approximately 4,000 patients with soft tissue sarcoma in Japan. Meanwhile, 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 novel mechanism of action. It was first approved for the treatment of metastatic breast cancer in the United States in November 2010, and is currently approved in approximately 60 countries including Japan and countries in Europe, the Americas and Asia.
Eisai remains committed to providing further clinical evidence for Halaven aimed at maximizing value of the drug as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.

< Notes to editors >

1. About Halaven (eribulin mesylate)
Halaven, a halichondrin class microtubule dynamics inhibitor with a novel mechanism of action, belongs to a class of antineoplastic agents, the halichondrins, which are natural products isolated from the marine sponge Halichondria okadai. It is believed to work by inhibiting the growth phase of microtubule dynamics without affecting the shortening phase and sequestering tubulin into nonproductive aggregates.
Halaven was first approved as a treatment for breast cancer in the United States in November 2010, and is now approved in nearly 60 countries worldwide, including Japan and countries in the Americas, Europe 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. In addition, Halaven has been designated as an orphan drug for soft-tissue sarcoma in the United States and Japan.

2. About Soft Tissue Sarcoma
Soft tissue sarcoma is a collective term for a diverse group of malignant tumors that occur throughout the soft tissue (fat, muscle, nerves, fibrous tissues and blood vessels) in the body. As the structures where the tumors originate are diverse, there are various types of soft tissue sarcoma, and the most common types include leiomyosarcoma, adipocytic 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 needs.

3. 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 versus dacarbazine in 452 patients (aged 18 or over) with locally advanced or recurrent and metastatic soft tissue sarcoma (one of two subtypes: leiomyosarcoma or adipocytic sarcoma) who had disease progression following standard therapies which must have included an anthracycline and at least one other additional regimen. Patients received either Halaven (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, Halaven demonstrated a statistically significant extension in the study’s primary endpoint of overall survival (OS) over the comparator treatment dacarbazine (Halaven median OS: 13.5 months vs dacarbazine median OS: 11.5 months, Hazard Ratio (HR) 0.768 [95% CI=0.618-0.954], p=0.017). Furthermore, in the study’s secondary endpoint of progression-free rate at 12 weeks (PFR12wks), while there was a numerical difference in PFR12wks between the Halaven and dacarbazine arms (33% vs 29%), this was not statistically significant. Median progression-free survival was 2.6 months in both arms.
In this study, the most common treatment-emergent adverse events observed in the Halaven arm were fatigue or asthenia, neutropenia, nausea, alopecia, and peripheral neuropathy, which was consistent with the known side-effect profile of Halaven.