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TESARO Announces U.S. FDA Approval of VARUBI(TM) (rolapitant) for Nausea and Vomiting Associated With Cancer Chemotherapy

On September 2, 2015 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has approved VARUBI (rolapitant) in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy (Press release, TESARO, SEP 2, 2015, View Source [SID:1234507385]).

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VARUBI is a selective and competitive antagonist of human substance P/neurokinin 1 (NK-1) receptors, with a plasma half-life of approximately seven days. Results from three Phase 3 trials of VARUBI demonstrated a significant reduction in episodes of vomiting or use of rescue medication during the 25 to 120 hour period following administration of highly emetogenic and moderately emetogenic chemotherapy regimens. In addition, patients who received VARUBI reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting or retching over multiple cycles of chemotherapy. A 180 milligram dose of VARUBI is to be administered approximately one to two hours prior to chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone. No dosage adjustment is required for dexamethasone, a CYP3A4 substrate, when administering VARUBI.

"The approval of VARUBI, our first product, represents a significant milestone in TESARO’s evolution into an integrated biopharmaceutical company with strong development and commercialization capabilities," said Lonnie Moulder, CEO of TESARO. "Results from the Phase 3 trials of VARUBI demonstrated that patients receiving emetogenic chemotherapy agents, including platinum and cyclophosphamide-containing regimens, benefitted from the addition of VARUBI to their antiemetic regimen. Data from multiple well-controlled trials demonstrate that patients who receive only a 5-HT3 receptor antagonist and dexamethasone often continue to suffer from nausea and vomiting for several days following chemotherapy administration. Patient surveys and our primary market research also point to the high rate of CINV and its potentially debilitating effects. We look forward to expanding the awareness of CINV and working with healthcare providers to make this important medicine available to patients during the fourth quarter."

"While important strides in preventing nausea and vomiting associated with chemotherapy have been made, still up to half of patients receiving emetogenic cancer chemotherapy can experience delayed CINV," said Richard J. Gralla, M.D., Professor of Medicine at Albert Einstein College of Medicine in New York. "Because NK-1 receptors are key drivers of CINV, especially in the delayed Phase, NK-1 receptor antagonists such as VARUBI, when combined with a 5-HT3 receptor antagonist and a corticosteroid, provide enhanced protection from CINV, and do so in the delayed timeframe where the most help is needed."

The full prescribing information for VARUBI will be available at www.VarubiRx.com.

About Chemotherapy-Induced Nausea and Vomiting (CINV)

Chemotherapy-induced nausea and vomiting is a debilitating, yet often preventable, side effect of chemotherapy.

Up to 50% of patients undergoing highly or moderately emetogenic chemotherapy experience delayed CINV (25 to 120 hours post chemotherapy)—even when prescribed a 5-HT3 receptor antagonist and corticosteroid.

Blocking both 5-HT3 and NK-1 receptors has been shown to offer better control of nausea and vomiting than inhibiting 5-HT3 receptors alone. Adding a single dose of VARUBI to an antiemetic regimen, including a 5-HT3 receptor antagonist and corticosteroid, further improves prevention of CINV in the delayed Phase following chemotherapy.

About the VARUBI (Rolapitant) Clinical Program

The superior efficacy of VARUBI was established in multiple randomized, well-controlled, blinded clinical trials that enrolled more than 2,500 patients. VARUBI, when administered in combination with a 5-HT3 receptor antagonist and dexamethasone, was superior to a 5-HT3 receptor antagonist and dexamethasone in preventing CINV in patients receiving either moderately or highly emetogenic chemotherapy.

The clinical profile of VARUBI in cisplatin-based highly emetogenic chemotherapy (HEC) was confirmed in two identical Phase 3 studies: HEC1 and HEC2. Both trials met their primary endpoint of complete response (CR), and demonstrated statistical superiority of rolapitant 180 mg compared to active control (5-HT3 receptor antagonist + dexamethasone) in the delayed Phase (25-120 hours) of CINV. In HEC1, 264 patients received rolapitant 180 mg and 262 received control. The proportion of patients achieving a CR was 72.7% vs. 58.4% (p= < 0.001). In HEC2, 271 patients received rolapitant and 273 received control. The proportion of patients achieving a CR was 70.1% vs. 61.9% (p=0.043). The most common adverse reactions (≥3%) among patients receiving cisplatin-based chemotherapy were neutropenia (9% VARUBI vs. 8% control), hiccups (5% vs. 4%), and abdominal pain (3% vs. 2%).

A Phase 3 trial was also conducted to evaluate rolapitant 180 mg compared to active control in 1,332 patients receiving moderately emetogenic chemotherapy regimens, including anthracycline/cyclophosphamide combinations, carboplatin, irinotecan, pemetrexed, oxaliplatin, and doxorubicin. This trial met its primary endpoint of CR, and demonstrated statistical superiority of rolapitant 180 mg compared to active control (5-HT3 receptor antagonist + dexamethasone) in the delayed Phase of CINV. The proportion of patients achieving a CR was 71.3% vs 61.6% (p= < 0.001). The most common adverse reactions (≥3%) among patients receiving these chemotherapies were decreased appetite (9% VARUBI vs. 7% control), neutropenia (7% vs. 6%), dizziness (6% vs. 4%), dyspepsia (4% vs. 2%), urinary tract infection (4% vs. 3%), stomatitis (4% vs. 2%), and anemia (3% vs. 2%).

Primary data from the three Phase 3 studies have recently been published online ahead of print in Lancet Oncology, the analysis of the non-AC MEC population was presented at the 2015 annual meeting for the Multinational Association for Supportive Care in Cancer, and commentary has been provided in Nature Reviews Clinical Oncology.

VARUBI Additional Safety Information

VARUBI is contraindicated in patients receiving thioridazine, a CYP2D6 substrate with a narrow therapeutic index.

Use of VARUBI should be avoided in patients who are receiving pimozide, a CYP2D6 substrate with a narrow therapeutic index. Adverse reactions should be monitored if concomitant use of VARUBI and other CYP2D6 substrates with a narrow therapeutic index cannot be avoided. The inhibitory effect of VARUBI on CYP2D6 lasts for at least 7 days and may last longer after administration of a single dose of VARUBI.

VARUBI is available by prescription only.

About VARUBI

VARUBI is a substance P/neurokinin-1 (NK-1) receptor antagonist indicated in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. NK-1 receptors are highly concentrated in the brain and bind neurokinin substance P. Activation of NK-1 receptors plays a central role in nausea and vomiting induced by emetogenic stimuli, including certain cancer chemotherapies. A Positron Emission Tomography (PET) study with rolapitant in normal, healthy volunteers demonstrated that rolapitant crosses the blood brain barrier and occupies brain NK-1 receptors at high levels for up to 120 hours. VARUBI has a half-life of approximately 7 days, which may contribute to the ability of a single dose of VARUBI to cover the entire delayed CINV Phase (25-120 hours).

An intravenous formulation of rolapitant is also being developed. TESARO licensed exclusive rights for the development, manufacture, commercialization and distribution of VARUBI (rolapitant) from OPKO Health, Inc.

Loxo Oncology Announces FDA Orphan Drug Designation Granted to LOXO-101 for Treatment of Soft Tissue Sarcoma

On September 2, 2015 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company focused on the discovery, development, and commercialization of targeted cancer therapies, reported that the United States Food and Drug Administration (FDA) has granted the company orphan drug designation for LOXO-101 for treatment of patients with soft tissue sarcoma (Press release, Loxo Oncology, SEP 2, 2015, View Source [SID:1234507381]).

Soft tissue sarcomas are cancers of the body’s connective or supportive tissues, such as cartilage, fat, muscle, fibrous tissue, and blood vessels. The FDA’s Office of Orphan Drug Products grants orphan drug designation to support the development of medicines for underserved patient populations, or rare disorders, that affect fewer than 200,000 people in the United States. Orphan drug designation provides to Loxo certain benefits, including market exclusivity upon regulatory approval if received, exemption of FDA application fees and tax credits for qualified clinical trials.

About LOXO-101

LOXO-101 is a potent, oral, selective inhibitor of tropomyosin receptor kinase (TRK) signaling molecules. The TRK family (TRKA, TRKB, and TRKC) has been implicated in diverse tumor types such as lung cancer, head and neck cancer, melanoma, colorectal cancer, sarcoma, and breast cancer. LOXO-101 was built specifically to inhibit TRK and is currently the only selective TRK inhibitor in clinical development. LOXO-101 is currently being evaluated in a Phase 1 dose escalation trial for patients with advanced solid tumors.

Incyte Announces Global License Agreement with Jiangsu Hengrui Medicine for SHR-1210, an Investigational Anti-PD-1 Monoclonal Antibody

On September 2, 2015 Incyte Corporation (Nasdaq: INCY) reported a global license and collaboration agreement with Jiangsu Hengrui Medicine Co., Ltd. for the development and commercialization of SHR-1210, an investigational anti-PD-1 monoclonal antibody (Press release, Incyte, SEP 2, 2015, View Source [SID:1234507380]).

Under the agreement, Incyte will have the exclusive development and commercialization rights to SHR-1210 worldwide, with the exception of Mainland China, Hong Kong, Macau, and Taiwan. SHR-1210 is expected to enter proof-of-concept studies for the treatment of patients with advanced solid tumors in the coming months.

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"The addition of this anti-PD-1 candidate to our early stage portfolio reinforces our commitment to cancer patients and further diversifies our clinical development programs," stated Hervé Hoppenot, President and Chief Executive Officer of Incyte. "We continue to make excellent progress in the multiple clinical trials underway across our existing portfolio, including our strategic collaborations."

Piaoyang Sun, Chairman of the Board of Hengrui, added, "Both Incyte and Hengrui are dedicated to cancer immunotherapy and are investigating several relevant biological targets in the area. The addition of SHR-1210 is an excellent fit to Incyte’s oncology portfolio, and we are pleased to see Incyte’s commitment to this PD-1 program. Combining the expertise and resources of both companies can accelerate the development of SHR-1210."

Terms of the Agreement

Under the terms of the agreement, Incyte will acquire development and commercialization rights to SHR-1210 worldwide, with the exception of Mainland China, Hong Kong, Macau, and Taiwan, in exchange for an upfront payment of $25 million. The terms also include potential milestone payments of up to $770 million to Hengrui, consisting of $90 million for regulatory approval milestones, $530 million for commercial performance milestones, and $150 million based on clinical superiority. The terms also include tiered royalties to Hengrui on net sales of SHR-1210 in Incyte territories. Under the Agreement, Incyte and Hengrui will assume all financial obligations associated with the development and commercialization of SHR-1210 in their respective territories.

About Anti-PD-1 Monoclonal Antibodies

Monoclonal antibodies targeting PD-1 enhance anti-tumoral immunity and are being developed for the treatment of cancer. Many tumor cells express PD-L1, an immunosuppressive PD-1 ligand. Inhibition of the interaction between PD-1 and PD-L1, known as immune checkpoint blockade, can enhance T-cell responses and mediate preclinical antitumor activity.1

For this transaction, Incyte was advised by Morgan Lewis, and Hengrui was advised by Wilson Sonsini Goodrich & Rosati.

EISAI CLEARS ALL-CASE SURVEILLANCE CONDITION FOR APPROVAL OF ANTICANCER DRUG GLIADEL(R) 7.7MG IMPLANT

On September 2, 2015 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that it has received notification from Japan’s Ministry of Health, Labour and Welfare (MHLW) to the effect that the "all-case surveillance" survey condition required for approval of Gliadel 7.7mg Implant (carmustine, "Gliadel") has been lifted (Press release, Eisai, SEP 2, 2015, View Source [SID:1234507378]).

In September 2012, the MHLW approved Gliadel indicated for malignant glioma with the following condition for approval: "Because of the very limited number of subjects treated in the Japanese clinical trials, the applicant is required to conduct all-case drug use-results survey until data from a certain number of patients are accumulated after market launch, in order to identify the background information of patients treated with the product and collect safety and efficacy data on the product in the early post-marketing period, and thereby take necessary measures to ensure proper use of the product."

The MHLW lifted this condition for approval after evaluating safety and efficacy data submitted by Eisai from patients with malignant glioma (558 cases for safety analysis, 536 cases for efficacy analysis). According to the results of the evaluation, the MHLW determined that the conditions for approval have been met.

Gliadel is the only sustained-release formulation approved for intracranial implantation in Japan. Each wafer contains the nitrosourea alkylating agent carmustine distributed in a biodegradable polymer matrix. Implanting the agent into the brain following surgical removal of malignant glioma allows for direct delivery of chemotherapy to the tumor site, allowing the agent to be used prior to initiating radiation, chemotherapy and other standard therapies. Gliadel is manufactured and distributed by Eisai, and the product is co-promoted by Eisai and Nobelpharma Co., Ltd.

Eisai will continue to promote and provide information on the proper use of Gliadel while making further contributions to improve the quality of life of patients.

DelMar Pharmaceuticals Announces Expansion of VAL-083 Development Program to Include Ovarian Cancer

On September 2, 2015 DelMar Pharmaceuticals, Inc. (OTCQX: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported that it will present an abstract entitled, "A Comparison of the Mechanisms and Cytotoxic Activity of Dianhydrogalactitol (VAL-083) to Cisplatin in Ovarian Tumor Models Harboring Wild-type and Mutant p53," at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Advances in Ovarian Cancer Research: Exploiting Vulnerabilities Conference being held October 17-20, 2015 in Orlando, FL (Press release, DelMar Pharmaceuticals, SEP 2, 2015, View Source [SID:1234507377]).

The presentation will summarize VAL-083’s potential as a new treatment for ovarian cancer in the context of DelMar’s recent research and historical data from prior NCI-sponsored clinical trials.

"These data have been developed in collaboration with researchers at MD Anderson Cancer Center and are aligned with our business model to leverage historical clinical proof-of-concept with modern biological data to solve modern unmet medical needs in the treatment of cancer," said Jeffrey Bacha, DelMar’s president and CEO.

DelMar Pharmaceuticals is currently conducting a Phase II clinical trial with VAL-083 for the treatment of refractory glioblastoma multiforme (GBM). Interim data from this trial presented at the American Association of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual meeting demonstrated a promising dose-response trend in patients with recurrent GBM. DelMar will present the next update of its GBM program at the 2nd International Symposium on Clinical and Basic Research in Glioblastoma, being held September 9-12, 2015 in Toledo, Spain.

The Company has also announced plans to initiate clinical development with VAL-083 in non-small cell lung cancer (NSCLC), which will be funded through DelMar’s collaboration with Guangxi Wuzhou Pharmaceutical (Group) Co. Ltd. Details of this trial will be presented at the 16th World Conference on Lung Cancer being held September 7 – 9 in Denver, Colorado.

About VAL-083

VAL-083 is a "first-in-class", small-molecule chemotherapeutic. In more than 40 Phase I and II clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated safety and efficacy in treating a number of cancers including lung, brain, cervical, ovarian tumors and leukemia. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia (CML) and lung cancer and has received orphan drug designation in Europe and the U.S. for the treatment of gliomas.

DelMar is currently studying VAL-083 in a multi-center Phase I/II clinical trial for patients with refractory glioblastoma multiforme (GBM) in accordance with the protocol that has been filed with the U.S. Food and Drug Administration (FDA) at five clinical centers in the United States: Mayo Clinic (Rochester, MN); UCSF (San Francisco, CA) and three centers associated with the Sarah Cannon Cancer Research Institute (Nashville, TN, Sarasota, FL and Denver, CO). As a potential treatment for glioblastoma, VAL-083’s mechanism of action appears to be unaffected by the expression of MGMT, a DNA repair enzyme that is implicated chemotherapy resistance and poor outcomes following front-line treatment with Temodar (temozolomide).