Spectrum Pharmaceuticals Begins Enrolling Patients in Registrational Trial of SPI-2012, a Novel, Long Acting G-CSF in Patients with Breast Cancer

On January 29, 2016 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations and a primary focus in Hematology and Oncology, reported the Company has initiated the planned registrational trial for SPI-2012 (eflapegrastim), its novel, long-acting G-CSF (Press release, Spectrum Pharmaceuticals, JAN 29, 2016, View Source [SID:1234508908]). This trial will evaluate the safety and efficacy of SPI-2012 as a treatment for chemotherapy-induced neutropenia in patients with breast cancer, and will serve as the basis for the Biologics License Application (BLA) filing.

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"The initiation of the registration trial for SPI-2012 is a significant milestone in the history of our company," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "Revenues from our current marketed drugs have helped us invest in this exciting technology that opens the door for us to a blockbuster oncology market. In parallel, Spectrum has built a strong commercial infrastructure with specialized expertise in this indication that positions us well to aggressively compete in this market."

"I am excited to be the lead investigator for this important study, and about the potency and safety of SPI-2012 as demonstrated in Phase 2," said Lee S. Schwartzberg, M.D., FACP Professor of Medicine and Division Chief, Hematology Oncology, The University of Tennessee Health Science Center, and Executive Director, UT/West Cancer Center. "The LAPSCOVERY technology confers long-acting properties and increased bone marrow uptake through decreased renal and vascular clearance, as well as Fc-mediated transport of G-CSF. We look forward to a successfully conducted Phase 3 trial of SPI-2012. I believe this novel biologic drug, if approved, would be a very valuable addition to our supportive care armamentarium for cancer patients receiving myelosuppressive cytotoxic chemotherapy."

"SPI-2012 is a third generation agent for the treatment of neutropenia that has shown promising results in Phase 2 trials," said, Jeffrey L. Vacirca, M.D., FACP CEO, Managing Partner & Chief of Clinical Research at North Shore Hematology/Oncology Associates and Vice-President, Community Oncology Alliance. "In the Phase 2 trial, the duration of severe neutropenia was equivalent to pegfilgrastim at the medium dose and superior at the high dose. No new or significant dose-related toxicities have been observed in over 230 patients who have been treated with SPI-2012, and the incidence of adverse events has been similar to pegfilgrastim."

In accordance with the SPA, this registrational, Phase 3 or ADVANCE study (RAnDomized Trial of SPI-2012 Versus Pegfilgrastim in the Management of Chemotherapy Induced Neutropenia in Breast CANCEr Patients Receiving Docetaxel and Cyclophosphamide) is a multicenter, randomized, active controlled trial that will enroll 580 newly diagnosed early-stage breast cancer patients, who will receive adjuvant or neoadjuvant chemotherapy every 21 days. Adjuvant chemotherapy is treatment given after primary surgical therapy to kill any remaining cancer cells and increase the chance of long-term disease-free survival; neoadjuvant chemotherapy is the administration of cytotoxic agents before surgical resection in early-stage breast cancer to shrink the tumor and potentially allow for breast-conserving surgery. SPI-2012 will be administered subcutaneously as a fixed dose equivalent to 3.6 mg of GCSF, which was selected based on the robust pharmacological and pharmacodynamic data from Phase 2. The primary study endpoint is the Duration of Severe Neutropenia (Absolute Neutrophil Counts [ANC] < 0.5×109/L) in Cycle 1 of chemotherapy, based on central laboratory assessment of ANC over the 21 day cycle. Secondary endpoints include the incidence of neutropenic complications, incidence of Febrile Neutropenia, Relative Dose Intensity, and safety.

About Special Protocol Assessments

A Special Protocol Assessment is a written agreement between a Sponsor and the U.S. Food and Drug Administration on the design, execution and analysis for a clinical trial that may form the basis of a new Biologics License Application or BLA. Final marketing approval depends upon the efficacy results, safety profile and an evaluation of the risk/benefit of treatment demonstrated in the Phase 3 clinical program.

About Breast Cancer

According to the American Cancer Society (ACS), breast cancer is the second most common form of cancer in women after skin cancer, and the second highest cause of female cancer deaths after lung cancer. Unfortunately, it is estimated that about 1 in 8 (12%) of women in the US will develop invasive breast cancer during their lifetime. In 2015 in the United States (US), an estimated 231,840 new cases of invasive breast cancer and 60,290 additional cases of in situ breast cancer will be diagnosed, and approximately 40,290 US women are expected to die from breast cancer. In addition, ~2,350 men are also expected to be diagnosed with breast cancer in 2015 with an estimated 440 deaths.

8-K – Current report

On January 29, 2016, in Tokyo, Japan (January 28, 2016, in San Francisco, CA), Medivation, Inc.’s collaboration partner Astellas Pharma Inc. (Astellas), reported its financial results for the quarter ended December 31, 2015 (Filing, 8-K, Medivation, JAN 29, 2016, View Source [SID:1234508921]).

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Astellas reported, among other things, that U.S. net sales of XTANDI (enzalutamide) capsules were $315.9 million for the quarter ended December 31, 2015 (Medivation’s fourth quarter), an increase of $85.7 million or 37% over the prior year quarter. The Astellas-reported net sales of $315.9 million increased by approximately one percent above the reported net sales of $313.0 million in the quarter ended September 30, 2015. Net sales for the quarter ended December 31 included an unfavorable adjustment of $2.6 million related to changes in Astellas’ estimate of prior period gross-to-net deductions against gross sales and an increase in channel partner inventory of just over one-half week of supply. As previously disclosed, the reported net sales of $313.0 million for the September quarter included a favorable adjustment of $17.9 million related to changes in Astellas’ estimate of prior period gross-to-net deductions against gross sales. Based on information provided by Astellas, the estimated growth in prescription demand from the quarter ended September 30, 2015 to the quarter ended December 31, 2015 was a low- to mid- single digit percentage. For the year ended December 31, 2015, U.S. net sales of XTANDI, as reported by Astellas, were $1.151 billion, an increase of $471.5 million or 69% over the prior year.

In its release, Astellas also reported net sales of XTANDI outside of the U.S. for the quarter ended December 31, 2015, expressed in various currencies. Medivation estimates such sales (expressed in U.S. dollars) were approximately $231 million for the quarter, which represents an increase of approximately 83% over the quarter ended December 31, 2014 and 13% over the quarter ended September 30, 2015. Medivation estimates net sales of XTANDI outside of the U.S. for the full year ended December 31, 2015 were approximately $757 million, an increase of approximately 99% over net sales for the year ended December 31, 2014. Fluctuating currency exchange rates reduced such estimated 2015 ex-U.S. net sales at the Astellas level, as expressed in U.S. dollars, by approximately 10% for the quarter and 14% for the year compared with the respective 2014 periods.

Based on the above, Medivation estimates worldwide net sales of XTANDI at the Astellas level were approximately $547 million for the quarter ended December 31, 2015 and $1.908 billion for the year ended December 31, 2015. Medivation earned the final sales milestone of $175 million under the collaboration with Astellas in the quarter ended December 31, 2015, based upon worldwide net sales exceeding $1.6 billion in the calendar year.

Medivation plans to report its own financial results for the quarter and year ended December 31, 2015, on February 25, 2016.

The information in this Item 7.01 is being furnished and shall not be deemed filed for purposes of Section 18 of the Exchange Act, or otherwise subject to the liability of that section, nor shall such information be deemed to be incorporated by reference in any registration statement or other document filed under the Securities Act of 1933, as amended, or the Exchange Act, except as otherwise stated in such filing.

ArQule Provides Proprietary Pipeline Update for AKT Inhibitors

On January 28, 2016 ArQule, Inc. (NASDAQ:ARQL) reported a pipeline update for its AKT inhibitors, including ARQ 092 and ARQ 751, both orally available, selective pan-AKT inhibitors (Press release, ArQule, JAN 28, 2016, View Source [SID:1234508895]).

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ARQ 092 – Lead AKT Inhibitor

The phase 1 trial for ARQ 092 in Proteus syndrome, which was opened for enrollment in November 2015, has completed dosing of its first cohort. The first cohort, consisting of three patients, is being observed for safety. The phase 1 trial is being conducted by our collaborators at the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH). Proteus syndrome is a rare disease that is characterized by overgrowth of the skeleton, skin, adipose tissue and central nervous system. ARQ 092 was recently granted orphan drug designation by the Food and Drug Administration (FDA) in this indication which impacts less than one in a million people worldwide.

Recently, a manuscript was published by the NHGRI of the NIH in Scientific Reports (available on-line at View Source) discussing pre-clinical research with ARQ 092 in Proteus syndrome. This pre-clinical study tested the efficacy of ARQ 092 in suppressing AKT signaling in cells and tissues from patients with Proteus syndrome. Reduced phosphorylation of AKT and downstream targets of AKT in a concentration-dependent manner were observed in as little as two hours without reduction in cell viability.

ArQule continues to enroll patients harboring AKT1 or PI3K mutations in the company sponsored phase 1b expansion cohort of its oncology trial. Cohorts for lymphoma and endometrial are fully enrolled. Thus far the company has observed five partial responses in the phase 1b portion of the trial, three of which occurred in patients whose tumors have AKT1 or PI3K mutations and two of which occurred in patients where the mutational status is unknown.

ARQ 751 – Next Generation AKT Inhibitor

ArQule received FDA approval of its investigational new drug (IND) application for ARQ 751, a next generation AKT inhibitor, in oncology. As published in PLOS ONE, (available on-line at View Source), ARQ 751 has demonstrated signal abrogation and efficacy in pre-clinical in vitro and in vivo models harboring AKT1 and PI3K mutations. The company expects to commence a phase 1 trial in oncology during the first half of 2016 targeting AKT1 and PI3K mutations.

"We are pleased with the two recent publications on our AKT program, and we look forward to further advancing our AKT pipeline in 2016 with ARQ 092 and our next generation AKT inhibitor, ARQ 751," said Brian Schwartz, Chief Medical Officer and Head of Research and Development at ArQule. "The understanding accumulated by us and our collaborators on our AKT program in oncology and rare diseases positions us for leadership in this class. We plan to explore opportunities to advance our trials in oncology as well as in rare over-growth indications beyond Proteus syndrome."

"2015 was an exciting year for ArQule as we were able to bring forward clinical results from our proprietary pipeline which now includes two orphan drug designations from the FDA," said Paolo Pucci, Chief Executive Officer at ArQule. "Looking ahead into 2016, we expect the interim analysis for the tivantinib phase 3 METIV-HCC trial to occur early in the second quarter, and we also expect to be able to make decisions on next steps in clinical development for ARQ 092 in oncology and Proteus syndrome, as well as for ARQ 087 in intrahepatic cholangiocarcinoma (iCCA)."

About Proteus Syndrome

According to the patient advocacy and support group, the Proteus syndrome Foundation (View Source), the condition was named for Proteus, the Greek god who could transform his shape. Patients experience changes in the shapes of certain body structures over time, including abnormal, often asymmetric, massive growth (overgrowth) of the skeleton, skin, adipose tissue and central nervous system out of proportion to the rest of the body, which may appear normal. Although patients may have minimal or no manifestations at birth, the disease develops and becomes apparent in early childhood (6-18 months) and rapidly progresses with intense growth in the first ten years of life. It is primarily a childhood-onset disease but there are very few living affected adults.

Proteus syndrome is a rare condition with an incidence of less than 1 in 1 million people worldwide. Only a few hundred individuals have been reported in the medical literature. At this time, there are more than 120 documented cases worldwide, but because not all cases are documented, it is not known how many individuals have this syndrome. The incidence of Proteus syndrome classifies it as a rare disorder, defined by the National Organization of Rare Diseases (NORD) as any disease affecting fewer than 200,000 Americans.

About the AKT Pathway, ARQ 092 and ARQ 751

ARQ 092 and ARQ 751 are orally bioavailable, selective small molecule inhibitors of the AKT kinases. The AKT pathway when abnormally activated is implicated in multiple oncogenic processes such as cell proliferation and apoptosis. This pathway has emerged as a target of potential therapeutic relevance for compounds that inhibit its activity, which has been linked to a variety of cancers as well as to select non-oncology indications.

ARQ 092, the lead compound in ArQule’s AKT program, has completed phase 1a clinical testing and has advanced into phase 1b expansion testing in cohorts of patients with endometrial cancer, lymphoma and tumors harboring either AKT or PI3K mutations. A number of next-generation compounds in the Company’s AKT program are in early to late stages of pre-clinical development. The company plans to initiate a phase 1 clinical trial in the first half of 2016 for ARQ 751, a next generation AKT inhibitor.

Sophiris Bio Reports Encouraging Preliminary Data from Phase 2a Proof of Concept Study in Localized Prostate Cancer

On January 28, 2016 Sophiris Bio Inc. (NASDAQ: SPHS) (the "Company" or "Sophiris"), a biopharmaceutical company developing PRX302 (topsalysin) for the treatment of urological diseases, reported the biopsy data at 6 months for the first seven patients to complete the Phase 2a proof-of-concept study in localized prostate cancer (Press release, Sophiris Bio, JAN 28, 2016, View Source [SID:1234508896]).

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A review of the biopsy data from the first seven men to complete the study showed that four patients experienced a response to treatment: One patient experienced complete ablation of the tumor where no evidence of the treated tumor remained on a targeted biopsy at 6 months; three patients experienced either a reduction in the maximum cancer core length or a reduction in Gleason pattern; three patients had no response to treatment.

"This new trial is very exciting — we have promising data showing that topsalysin can ablate cancer cells and we look forward to reviewing the results from the remaining 11 patients as they complete the study. We could be on the cusp of a new class of therapeutics for the focal treatment of localized prostate cancer," stated Professor Mark Emberton, Dean, Faculty of Medical Sciences, University College London and Honorary Consultant Urologist University College London Hospital NHS Foundation Trust.

Dr. Hashim Ahmed, Principal Investigator for the study, Division of Surgery and Interventional Sciences, University College London, said, "Topsalysin could offer a tissue-sparing cancer treatment that carries little in the way of side effects. This treatment has the potential to help men avoid radical treatments such as radiation therapy or complete removal of the prostate."

This one-time administration of topsalysin directly into a pre-identified clinically significant tumor appears to be well tolerated with no serious adverse events and no new safety signals being reported. This is consistent with safety observed in the 365 patients that have been treated with topsalysin in the Company’s BPH program to date.

"The biological activity that we have observed further validates the mechanism of action of topsalysin. We are gaining valuable experience on how we might best optimize both the delivery and dose of topsalysin based on lesion size, and the remaining patients to complete the study will help in that assessment," said Dr. Ahmed.

The ongoing Phase 2a proof of concept study is a single-center, open-label study at University College London, which is well known for the focal treatment of prostate cancer in the UK. In this study, previously obtained multiparametric magnetic resonance images (mpMRIs) of each patient’s prostate tumor lesions are mapped to real-time three-dimensional transrectal ultrasound. These images are used to guide the injection of topsalysin to treat a single, histologically-proven, clinically significant prostate cancer lesion. The primary objective of the study is safety and tolerability, and the key efficacy variable is the change in the treated lesion on targeted biopsy after 6 months. The study is designed to assess whether topsalysin has the potential to provide patients with clinically significant, localized, low to intermediate risk prostate cancer a tissue-sparing cancer treatment that carries little in the way of side effects. A total of 18 patients were enrolled and treated in this study. Sophiris expects to have final data on all patients by the end of the second quarter of 2016.

Webcast scheduled for today at 11:00 a.m. Pacific Time
The Sophiris management team will host a conference call and webcast today, January 28, at 11:00 a.m. Pacific Time to review the topsalysin prostate cancer data as well as the previously announced results of the topsalysin Phase 3 study in BPH. Dr. Hashim Ahmed, University College London and an investigator in the prostate cancer study, and Dr. Marc Gittelman, Director of South Florida Medical Research and investigator in the Phase 3 BPH study, will also participate in the call.

A live audio webcast will be accessible on the "Investor Relations" page of the Sophiris corporate website at www.SophirisBio.com. A replay will be available at the same location for 60 days.

About Prostate Cancer
Prostate cancer is the second most common form of cancer in men in the US with an estimated 220,800 new cases in 2015. Approximately 80 percent of patients in the US are diagnosed with localized disease. Research has shown that patients with early, localized disease have a low likelihood of the cancer spreading beyond the confines of the prostate; however, many men with clinically significant localized disease do choose to undergo radical treatment. Radical therapies include surgery to remove the entire prostate and/or radiation. Potential toxicities from radical treatments can be significant and permanent and include erectile dysfunction, urinary incontinence, and rectal toxicity.

Topsalysin for the Targeted Treatment of Localized Prostate Cancer
Topsalysin (PRX302) has the potential to provide a focal targeted therapy for the ablation of localized prostate cancer while potentially avoiding many of the complications and side effects associated with whole gland radical treatments. The increasing use of multi-parametric magnetic resonance imaging (mpMRI) and advances in mapping previously obtained mpMRI images with real-time three-dimensional ultrasound images enables physicians to more accurately locate tumors within the prostate when taking biopsies. This increases the accuracy with which men with clinically significant lesions are identified. It also enables the injection of an ablative agent, such as topsalysin, directly into previously identified clinically significant tumors located within the prostate. Topsalysin, an inactivated pore-forming protein, was engineered to be activated only by enzymatically-active PSA, which is present only in prostate tissue. The targeted focal treatment of prostate cancer is in line with current treatments for solid tumors such as breast and liver, where the goal is to remove the tumor and preserve as much of the organ as possible

8-K – Current report

On January 28, 2016 Eagle Pharmaceuticals, Inc. (Nasdaq: EGRX) reported that Teva Pharmaceuticals has commenced shipment of BENDEKA, (bendamustine hydrochloride) injection, a liquid, low-volume (50 mL) and short-time 10-minute infusion formulation of bendamustine (Filing, 8-K, Eagle Pharmaceuticals, JAN 28, 2016, View Source [SID:1234508898]). BENDEKA is approved for the treatment of patients with chronic lymphocytic leukemia (CLL) and for the treatment of patients with indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. Efficacy in CLL relative to first-line therapies other than chlorambucil has not been established.

According to Paul Rittman, Senior Vice President and General Manager, Teva Oncology, "With the launch of BENDEKA, Teva furthers our commitment to providing treatment options for patients with these rare forms of cancer. We believe BENDEKA represents an important benefit to both patients and healthcare providers, and are pleased it is now available. Based on the product profile, we expect BENDEKA to replace TREANDA liquid."

Under a February 2015 exclusive license agreement for BENDEKA, Teva is responsible for all U.S. commercial activities for the product including promotion and distribution.

The information furnished pursuant to Item 7.01 of this current report shall not be deemed to be "filed" for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended. As such, this information shall not be incorporated by reference into any of the Company’s reports or other filings made with the Securities and Exchange Commission. The furnishing of the information in this current report is not intended to, and does not, constitute a determination or admission by the Company that the information in this current report is material or complete, or that investors should consider this information before making an investment decision with respect to any security of the Company.

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