On June 1, 2016 Nektar Therapeutics (Nasdaq: NKTR) reported that it has entered into an agreement with Daiichi Sankyo Europe for Nektar’s investigational drug therapy, ONZEALD (etirinotecan pegol, NKTR-102), which has completed a Phase 3 clinical trial (the BEACON study) in patients with advanced breast cancer (Filing, 8-K, Nektar Therapeutics, JUN 1, 2016, View Source [SID:1234512942]). The agreement grants Daiichi Sankyo Europe exclusive rights to market ONZEALD in Europe (EEA), Switzerland and Turkey. Nektar Therapeutics will retain rights to ONZEALD in the United States and the rest of the world.

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Under the terms of the agreement, Nektar Therapeutics is entitled to an upfront payment of $20 million as well as an additional $60 million in milestone payments, based upon the achievement of European regulatory milestones and European sales of ONZEALD. Nektar is also entitled to significant double-digit royalties on net sales in Europe.

"This new collaboration with Daiichi Sankyo Europe allows Nektar to advance ONZEALD to a potential conditional approval and availability in Europe as early as next year, and also enables us to retain ownership of the drug in the U.S. and rest of world," said Howard W. Robin, President and Chief Executive Officer of Nektar Therapeutics. "We are pursuing conditional approval for ONZEALD based on highly promising data from our Phase 3 BEACON clinical trial in the pre-specified subgroup of patients with advanced breast cancer who have a history of brain metastases. A diagnosis of brain metastases in women with advanced breast cancer is devastating and there are no therapies approved to treat this specific patient population."

Nektar plans to submit an MAA filing in June 2016 seeking conditional approval from the European Medicines Agency (EMA) for the use of ONZEALD in the treatment of patients with advanced breast cancer and brain metastases. On May 26, 2016, the Committee for Medicinal Products for Human Use (CHMP) granted an accelerated assessment procedure for the planned ONZEALD filing, which provides for an accelerated MAA review timeline.

Nektar will be responsible for sponsoring and funding the confirmatory trial which will support the Marketing Authorization Application (MAA) filing for ONZEALD in Europe. The data from the confirmatory trial can be used by Nektar for a potential U.S. new drug application (NDA) filing for ONZEALD.

Breast cancer is the most frequently diagnosed cancer in women worldwide with nearly 1.7 million new cases diagnosed in 2012.1 There are approximately 250,000 newly-diagnosed cases of breast cancer in the United States and 470,000 in Europe each year. 1 Approximately 10-30 percent of patients with advanced breast cancer are also diagnosed with brain metastases. 2

Nektar’s planned MAA filing is based upon data from a subgroup of patients from the completed BEACON study of single-agent ONZEALD in patients with advanced breast cancer. In this subgroup of 67 patients who also had a history of brain metastases, treatment with single-agent ONZEALD resulted in an improvement in median overall survival (OS) of 5.2 months compared to treatment with a single-agent chemotherapy of physician’s choice (TPC) (10 months vs. 4.8 months, P < 0.01). TPC included a choice of ixabepilone, vinorelbine, gemcitabine, eribulin or a taxane. In the planned primary analysis for the overall patient population in the BEACON study, ONZEALD median OS was 2.2 months longer than TPC (12.4 months vs. 10.3 months, P= 0.08).3 In the overall patient population in the BEACON study, fewer patients in the ONZEALD arm had grade 3 or worse adverse events (AEs) than those in the TPC arm (204 [48%] vs. 256 [63%]; p<0·0001).3 The most common grade 3 and above AEs observed with ONZEALD were diarrhea (9.6%), neutropenia (9.6%), anemia (4.7%) and fatigue (4.5%). The most common grade 3 and above AEs observed with TPC were neutropenia (30.8%), anemia (4.7%), and dyspnea (4.4%).

In order to satisfy the EMA’s requirement for additional controlled data with the MAA for conditional approval, Nektar will sponsor a global, randomized Phase 3 trial of ONZEALD in approximately 350 patients with advanced breast cancer and brain metastases. The trial will compare ONZEALD to TPC and the primary endpoint in the trial will be OS. The trial will include a pre-specified interim analysis for OS which is to be conducted after 130 events have been observed in the trial. The U.S. Food and Drug Administration has also reviewed the Phase 3 study design with the Statistical Analysis Plan, and indicated the trial could serve as a potential registrational study by Nektar for purposes of seeking approval of ONZEALD to treat this patient population in the U.S.
The EMA may grant conditional marketing authorization when the potential treatment addresses a severely debilitating disease with an unmet medical need, has a positive benefit to risk profile, and the benefits to public health of its immediate availability outweigh the risks inherent in the fact that additional data are still required. Ongoing or new studies must be completed with the objective of confirming that the benefit to risk balance is positive. A conditional approval granted by the EMA is renewed on an annual basis until all obligations have been fulfilled, at which point a full approval may be granted by the EMA.

For additional terms and conditions of the licensing agreement between Nektar and Daiichi Sankyo Europe, please refer to the Current Report on Form 8-K filed today with the Securities and Exchange Commission.

About ONZEALD (etirinotecan pegol) (formerly NKTR-102)

ONZEALD is the first long-acting topoisomerase I inhibitor with an extended half-life and a unique structure that is designed to concentrate the drug in tumors. In patients, ONZEALD leads to greatly prolonged plasma SN38 exposure compared with irinotecan (elimination half-life of 37 days compared with 2 days) yet peak SN38 concentrations are at least 5- to 10-times less, which may also result in a favorable tolerability profile. ONZEALD was evaluated in a Phase 3, open-label, randomized, multicenter study (the BEACON study) that enrolled 852 women with locally recurrent or metastatic breast cancer, who have previously been treated with an anthracycline, taxane and capecitabine therapies.

On June 1, 2016 Regulus Therapeutics Inc. (NASDAQ: RGLS), a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs (miR), reported that it has expanded its clinical trial collaboration agreement with GSK (NYSE: GSK) for the development of RG-101, Regulus’ wholly-owned, GalNAc-conjugated anti-miR that targets miR-122 (Press release, Regulus, JUN 1, 2016, View Source [SID:1234512943]). In the expanded collaboration, the companies plan to conduct a multi-centered, randomized, dose-ranging Phase II study evaluating the combination of RG-101 and GSK’s long-acting parenteral ("LAP") formulation of GSK2878175 as a potential single-visit cure in patients chronically infected with HCV. This study will be conducted outside the United States and is planned to begin in the fourth quarter of 2016. Based on predicted enrollment rates, interim results from this expanded collaboration should be available in the second half of 2017, enabling a potential initiation of a pivotal study in late 2017. As with the initial collaboration, both parties will share equally in the costs associated with the study. Neither Regulus nor GSK has any further obligations or commitments to each other beyond this expanded clinical collaboration agreement.

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"We are very pleased to expand our working collaboration with GSK. This is an important next step to advance the scientific understanding of the potential for a combination therapy to achieve a single-visit cure for HCV," said Paul Grint, M.D., President and CEO of Regulus. "The market research conducted to date indicates that a potential single visit cure would be a highly preferred product profile to existing regimens."

Zhi Hong, Senior Vice President and Head of the Infectious Diseases Therapy Area, GSK, commented, "We are excited about the potential of this combination to provide people living with HCV a new treatment option that could be delivered in a single visit. Together with Regulus, we are taking another step forward to proving this novel concept."

Earlier this year, pursuant to the initial GSK-Regulus clinical trial collaboration agreement, Regulus began enrolling patients in an open-label Phase II clinical trial combining RG-101 and GSK2878175 for the treatment of HCV to evaluate the potential to achieve sustained viral responses post treatment with a single subcutaneous administration of 4 mg/kg of RG-101 in combination with daily oral administrations of 20 mg of GSK2878175 for up to 12 weeks in treatment-naïve patients chronically infected with HCV genotypes 1 and 3. Regulus and GSK anticipate reporting interim results from this study by year-end.

About microRNAs

The discovery of microRNAs in humans during the last decade is one of the most exciting scientific breakthroughs in recent history. microRNAs are small RNA molecules, typically 20 to 25 nucleotides in length, that do not encode proteins but instead regulate gene expression. More than 800 microRNAs have been identified in the human genome, and over two-thirds of all human genes are believed to be regulated by microRNAs. A single microRNA can regulate entire networks of genes. As such, these molecules are considered master regulators of the human genome. microRNA expression, or function, has been shown to be significantly altered or dysregulated in many disease states, including oncology, fibrosis, metabolic diseases, immune-inflammatory diseases and HCV. Targeting microRNAs with anti-miRs, chemically modified, single-stranded oligonucleotides, offers a unique approach to treating disease by modulating entire biological pathways and may become a new and major class of drugs with broad therapeutic application.

On May 31, 2016 Janssen-Cilag International NV (Janssen) reported that the European Commission (EC) has approved IMBRUVICA (ibrutinib) for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) (Press release, Johnson & Johnson, MAY 31, 2016, View Source [SID:1234512902]).1 This broadens the indication beyond the initial CLL approval by the EC in October 2014. Ibrutinib is now approved for all patients with CLL, expanding the number of patients who may benefit from this treatment.

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The expanded ibrutinib indication is based on data from the Phase 3, randomised, open-label RESONATE-2 trial, as published in The New England Journal of Medicine (NEJM) in 2015.

"Ibrutinib has shown remarkable improvements in overall survival, progression-free survival and response rates compared with chlorambucil," said Professor Paolo Ghia, Associate Professor of Internal Medicine at Università Vita-Salute San Raffaele in Milan, Italy. "The RESONATE-2 data indicate that ibrutinib can provide a much-needed first line treatment alternative for many patients."

Results from the RESONATE-2 study showed that ibrutinib significantly prolonged overall survival (OS) (HR=0.16, 95 percent CI 0.05 to 0.56; P=0.001), with 98 percent of patients still alive after two years, compared to 85 percent for patients randomised to the chlorambucil arm.2 The median progression-free survival (PFS) was not reached for patients receiving ibrutinib versus 18.9 months for those in the chlorambucil arm, representing a statistically significant 84 percent reduction in the risk of death or progression in the ibrutinib arm (HR=0.16, 95 percent CI 0.09 to 0.28; P<0.001).2 The overall safety of ibrutinib in the treatment-naïve CLL patient population was consistent with previously reported studies.3 The most common adverse reactions (ARs) (=20 percent) of any Grade in the RESONATE-2 trial for ibrutinib were diarrhoea (42 percent), fatigue (30 percent), cough (22 percent) and nausea (22 percent).2

"The availability of a targeted therapy as an initial treatment is a tremendous step forward for people affected by CLL and has been long-awaited by the CLL community," said Nick York, patient advocate, CLL Advocates Network (CLLAN). "Many patients are considered unsuitable for the current first line standard of care so there is a real need for new, effective treatment options for these patients."

Despite the availability of effective first line chemo-immunotherapy regimens for CLL, many patients, especially the elderly, cannot tolerate their adverse effects.3 CLL is generally a slow-growing blood cancer of the white blood cells.4 The prevalence rate of CLL in Europe among men and women is approximately 5.87 and 4.01 cases per 100,000 persons per year, respectively.5,6 CLL is predominantly a disease of the elderly, with a median age of 72 at diagnosis.7

"The body of clinical and real-world evidence in support of ibrutinib’s patient benefits continues to grow, and with this first line approval we are so pleased to be able to alter the treatment landscape and options for CLL patients," said Jane Griffiths, Company Group Chairman, Janssen Europe, Middle East and Africa. "We now look forward to working with health authorities across the region to make ibrutinib available to patients in this indication as soon as possible."

This latest EC approval follows the decision by the U.S. Food and Drug Administration on 04 March 2016 to approve the expanded use of ibrutinib capsules for treatment-naïve patients with CLL.

Ibrutinib is co-developed by Cilag GmbH International, a member of the Janssen Pharmaceutical Companies, and Pharmacyclics LLC, an AbbVie company. Janssen affiliates market ibrutinib in EMEA (Europe, Middle East and Africa) as well as the rest of the world, except for the United States, where Janssen Biotech, Inc. and Pharmacyclics co-market it. Janssen and Pharmacyclics continue to support an extensive clinical development program for ibrutinib, including Phase 3 study commitments in multiple patient populations.

#ENDS#
About ibrutinib

Ibrutinib is a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, which works by forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B cells.8 By blocking this BTK protein, ibrutinib helps kill and reduce the number of cancer cells, thereby delaying progression of the cancer.9

Ibrutinib is currently approved in Europe for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL); for previously untreated adult patients with chronic lymphocytic leukaemia (CLL) or those who have received at least one prior therapy; and in adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy.10

Additional uses are under clinical investigation but have not yet been granted regulatory approval.

Please see the ibrutinib summary of product characteristics for further information.

About CLL

CLL is a chronic disease; median overall survival ranges between 18 months and more than 10 years, according to the stage of disease.11 The disease eventually progresses in the majority of patients, and patients are faced with fewer treatment options each time. Patients are often prescribed multiple lines of therapy as they relapse or become resistant to treatments.

On May 31, 2016 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported details relating to two poster presentations at the upcoming 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 3-7 in Chicago, Illinois (Press release, Onconova, MAY 31, 2016, View Source [SID:1234512903]).

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Rationale and Mechanism of Action for Rigosertib/Azacitidine Combination Therapy

Poster Presentation with Discussion*
Abstract Number: 7020
Title: Rigosertib (RIG) in combination with azacitidine (AZA) to modulate epigenetic effects and to overcome clinical resistance to hypomethylating agents (HMA) in myelodysplastic syndromes (MDS).
Session Name: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Date: Monday, June 6, 2016
Time and Location: 8:00 AM — 11:30 AM, McCormick Place, Hall A
Presenter: Pratima Chaurasia, PhD, Icahn School of Medicine at Mount Sinai

*Poster discussion session on Monday, June 6, 2016 from 11:30 AM — 12:45 PM

Design of Phase 3 INSPIRE Trial for Second-line Higher-risk Myelodysplastic Syndromes

Poster Presentation
Abstract Number: TPS7077
Title: INSPIRE: A randomized phase III trial of intravenous rigosertib in patients with higher-risk myelodysplastic syndromes (HR-MDS) after failure of hypomethylating agents (HMAs)—Study design informed by subgroup analyses of ONTIME.
Session Name: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Date: Monday, June 6, 2016
Time and Location: 8:00 AM — 11:30 AM, McCormick Place, Hall A
Presenter: Guillermo Garcia-Manero, MD, MD Anderson Cancer Center, Houston, TX

On May 31, 2016 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that it has acquired Sividon Diagnostics, a leading breast cancer prognostic company, for €35 million upfront with the potential for €15 million in additional performance-based milestones (Press release, Myriad Genetics, MAY 31, 2016, View Source [SID:1234512945]). The transaction closed on May 31, 2016. Myriad expects the deal to be neutral to both revenue and earnings in fiscal year 2017. A discussion on the details and strategy underlying the transaction will be provided on a conference call today at 4:30 pm EDT.

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"Sividon brings to Myriad the best-in-class breast cancer prognostic test and strengthens our market leading oncology portfolio of high value personalized medicine products," said Mark C. Capone, president and CEO, Myriad Genetic Laboratories. "The EndoPredict test will be the foundational product of our newly initiated kit-based strategy and allow Myriad to leverage its global oncology distribution to bring this important test to patients worldwide."

"We are excited to be integrated with the global leader and pioneer in personalized medicine," said Christoph Petry, CEO of Sividon Diagnostics. "Myriad has the reimbursement, regulatory, and commercial expertise to make this product very successful, especially as we seek distribution in the United States and broader reimbursement coverage in Europe."

Sividon Diagnostics was spun out of Siemens Healthcare Diagnostics in 2010 as part of a management buyout. Their core EndoPredict product is a kit-based RNA expression test that evaluates 12 genes to assess the aggressiveness of breast cancer on a molecular level. The test is currently CE Marked on the Siemens Versant instrument, however, Myriad is transitioning the product to the Thermo Fisher QuantStudio platform as a key step in the international kit strategy. EndoPredict has been evaluated in 5 major studies incorporating more than 4,000 patients, utilized on a clinical basis in over 13,000 patients worldwide, and is extensively referenced in clinical guidelines across the globe. In a head-to-head study, it has been shown to outperform the prognostic ability of the leading first generation test while providing definitive answers with no intermediate results.

Benefits of the Transaction

Synergistic Product Within the 4in6 Strategy: EndoPredict evaluates the aggressiveness of breast cancer to help patients decide whether to safely forgo chemotherapy and will be added into our existing oncology commercial channel, creating significant opportunities for operating leverage.
Substantial Market Opportunity: Myriad believes the global market opportunity for EndoPredict is greater than $600 million with the majority of that market existing in major European countries, Canada, and the United States. We estimate that this market is less than 25 percent penetrated on a global basis and EndoPredict should benefit from a significant expansion in reimbursement in the coming years.
Best-in-Class Product: EndoPredict has been studied in approximately 4,000 patients and utilized in over 13,000 patients, and has consistently demonstrated the best ability to predict which patients are at low risk for distant metastases in both node negative and node positive patients. Additionally, the kit-based format provides unique advantages in the marketplace and EndoPredict will be the foundational product in Myriad’s global kit-based strategy.
Broadens Comprehensive Product Offering in Oncology: Myriad currently sells market leading tests in oncology for hereditary cancer and companion diagnostics. EndoPredict answers another important clinical question for breast cancer patients by identifying which can safely forgo chemotherapy. Oncology customers can increasingly rely on Myriad as a single source trusted advisor answering questions across the entire continuum of care with unmatched quality.
Financing
Myriad intends to fund the transaction entirely through cash on hand. At the end of the fiscal third quarter Myriad had cash and cash equivalents of $286 million on hand.