10-Q – Quarterly report [Sections 13 or 15(d)]

Amgen has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Amgen, APR 27, 2015, View Source [SID1234503189]).

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Data Safety Monitoring Board Recommends Continuation of Phase 3 Study of Zoptarelin Doxorubicin in Advanced Endometrial Cancer

On April 27, 2015 Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the "Company") reported that the independent Data Safety Monitoring Board ("DSMB") for the pivotal Phase 3 ZoptEC (Zoptarelin Doxorubicin in Endometrial Cancer) study with zoptarelin doxorubicin in women with advanced, recurrent or metastatic endometrial cancer, has completed a pre specified first interim futility analysis (Press release, AEterna Zentaris, APR 27, 2015, View Source;q=655 [SID:1234506576]). The DSMB has recommended that the Phase 3 study continue as planned.

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David Dodd, Chairman and CEO of Aeterna Zentaris, commented, "We are very pleased with this positive recommendation from the DSMB on our ZoptEC Phase 3 trial in endometrial cancer, and I would like to thank everyone involved in this project for their unwavering dedication. With approximately 90 % of patients enrolled at this time, we are well on our way of completing patient recruitment ahead of the anticipated timeline. We believe that zoptarelin doxorubicin has the potential to become the first FDA approved medical therapy for advanced, recurrent endometrial cancer This could result in its rapid adoption as a novel core therapy for patient treatment & management, and therefore, could represent a significant market opportunity for the Company. Moving forward, we are continuing to develop our commercialization plans regarding zoptarelin doxorubicin in this indication, including establishing additional partnerships in territories that won’t be pursued by Aeterna Zentaris. In addition, contingent on the success of the ZoptEC program, we have additional areas of interest for further therapeutic development, including ovarian, prostate and triple negative breast cancer. Our commitment is to ensure that patients and their physicians have such therapies that can potentially improve and extend the quality of lives."

The ZoptEC Phase 3 trial is an open-label, randomized-controlled study, comparing the efficacy and safety of zoptarelin doxorubicin, a hybrid molecule composed of a synthetic peptide carrier and a well known chemotherapy agent, doxorubicin, to doxorubicin alone. It is being conducted under a Special Protocol Assessment with the U.S. Food and Drug Administration ("FDA"). Patients are centrally randomized in a 1:1 ratio and receive either zoptarelin doxorubicin (267 mg/m2) or doxorubicin (60 mg/m2) intravenously, every 3 weeks and for up to 9 cycles. Response will be evaluated every 3 cycles during treatment, thereafter, every 12 weeks until progression. All patients will be followed for survival as the primary efficacy endpoint ("EP"). Secondary EPs include progression-free survival, objective response-rate, and clinical benefit rate.

At this time, sites initiation has been completed with over 120 sites in operation in North America, Europe and Israel. More than 465 patients out of an expected total of 500 have been recruited. A second interim analysis will be conducted according to protocol at approximately 192 events, with the final analysis planned at an anticipated 384 events.

For more information on this trial, please consult (ClinicalTrials.gov Identifier: NCT01767155; EudraCT No: 2012-005546-38; ZoptEC: Zoptarelin doxorubicin in endometrial cancer).

About Zoptarelin Doxorubicin

Zoptarelin doxorubicin represents a new targeting concept in oncology using a hybrid molecule composed of a synthetic peptide carrier and a well-known chemotherapy agent, doxorubicin. Zoptarelin doxorubicin is the first intravenous drug in advanced clinical development that directs the chemotherapy agent specifically to LHRH-receptor expressing tumors, which could result in a more targeted treatment with less damage to healthy tissue. The Company is currently conducting a ZoptEC (Zoptarelin doxorubicin in Endometrial Cancer) Phase 3 trial in women with advanced, recurrent or metastatic endometrial cancer, while zoptarelin doxorubicin is also in an investigator-initiated Phase 2 trial in prostate cancer. Aeterna Zentaris owns the worldwide rights to this compound except in China (including Hong Kong and Macau) where rights have been out-licensed to Sinopharm A-Think Pharmaceuticals, a subsidiary of Sinopharm, the largest medical and healthcare group in China and on Fortune’s Global 500 list. On April 16, 2015, the Company announced the filing of a patent application intended to strengthen the exclusivity of zoptarelin doxorubicin through a unique, significantly lower cost in the manufacturing process.

About Endometrial Cancer

Endometrial cancer is the most common gynecologic malignancy in developed countries and develops when abnormal cells amass to form a tumor in the lining of the uterus. It largely affects women over the age of 50 with a higher prevalence in Caucasians and a higher mortality rate among African Americans. According to the American Cancer Society, there will be more than 50,000 new cases of endometrial cancer in the U.S. alone in 2015, with about 20% of recurring disease.

Genmab Announces Phase III Study of Arzerra® Met Primary Endpoint of Improved Progression-Free Survival in Patients with Relapsed CLL

On April 27, 2015 Genmab reported that the top-line results from the Phase III COMPLEMENT 2 study showed that treatment with Arzerra (ofatumumab) plus fludarabine and cyclophosphamide met the primary endpoint of improved progression-free survival (PFS) in patients with relapsed CLL (p = 0.0036) compared to those given fludarabine and cyclophosphamide alone (Press release, Genmab, APR 27, 2015, View Source [SID:1234503192]). The safety profile observed in this study was consistent with other trials of ofatumumab and no new safety signals were observed.

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"We are pleased with the positive topline results in this pivotal study of ofatumumab in combination with fludarabine and cyclophosphamide in relapsed CLL. This outcome is good news for patients with CLL, a disease for which relapses are inevitable. We look forward to sharing additional data from the study at an upcoming medical conference and to discussions with the regulatory authorities in collaboration with Novartis," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About CLL
CLL, the most commonly diagnosed adult leukemia in Western countries, accounts for approximately 1 in 4 cases of leukemia1,2. Most CLL patients experience disease progression despite initial response to therapy and may require additional treatment3.

About COMPLEMENT 2
COMPLEMENT 2 (NCT00824265) is an open-label, two-arm, randomized, Phase III study, which included 365 patients in 18 countries with relapsed CLL. Patients in the study were randomized 1:1 to treatment with up to six cycles of ofatumumab in combination with fludarabine and cyclophosphamide or up to six cycles with fludarabine and cyclophosphamide alone.

The primary endpoint of the study was PFS, which was assessed by an Independent Review Committee (IRC) according to the International Workshop for Chronic Lymphocytic Leukaemia (iwCLL) updated 2008 National Cancer Institute-sponsored Working Group (NCIWG) guidelines4. Secondary endpoints included overall response rate, overall survival, patient reported outcomes, time to response, duration of response, time to progression, time to next therapy, safety assessments and quality of life.

Ofatumumab is not approved for this indication and Novartis will further analyze the data from the COMPLEMENT 2 study and plans to share the results with regulatory agencies to evaluate the potential for future regulatory filings.

About Arzerra
Arzerra (ofatumumab) is a human monoclonal antibody that is designed to target the CD20 molecule found on the surface of chronic lymphocytic leukemia (CLL) cells and normal B lymphocytes.

In the United States, Arzerra is approved for use in combination with chlorambucil for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate. In the European Union, Arzerra is approved for use in combination with chlorambucil or bendamustine for the treatment of patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy. Arzerra is also approved for first-line use in Russia, Iceland, Norway, Luxembourg and Brazil.

In more than 50 countries worldwide, Arzerra is also indicated as monotherapy for the treatment of patients with CLL who are refractory after prior treatment with fludarabine and alemtuzumab.

Arzerra is marketed under a co-development and collaboration agreement between Genmab and Novartis, as successor in interest to GSK.

Important Safety Information for Arzerra (ofatumumab)

Treatment with Arzerra may cause side effects, some of which are serious and life-threatening.

Treatment with Arzerra may cause a side effect called an infusion reaction, which may be serious. Before treatment with Arzerra, doctors will prescribe 3 types of medicine to their patients to help reduce the risk of an infusion reaction, including a steroid (to reduce swelling and other symptoms of inflammation), a pain reliever, and an antihistamine (to reduce allergic reactions). Even though patients receive these medicines, they may still have an infusion reaction. If an infusion reaction occurs, the doctor will stop their patient’s treatment with Arzerra so the infusion reaction can be treated. Patients should tell their doctor or seek medical treatment right away if they have any of these symptoms while receiving Arzerra or within 24 hours after receiving Arzerra: fever, chills, rash, hives, chest pain, back pain, stomach pain, swelling, dizziness, blurred vision, drowsiness, headache, cough, wheezing, or trouble breathing.

Treatment with Arzerra may cause hepatitis B virus (HBV) infection to reoccur, which may cause serious liver problems and death. Patients who are newly exposed to HBV during or following treatment with Arzerra may experience serious liver problems and death. Patients should tell their doctor if they have had HBV infection or are a carrier of HBV. Before starting Arzerra, doctors will do a blood test to check for HBV infection. In some patients, additional blood tests may be done during and several months after treatment. Patients should call their doctor right away if they feel more tired than usual or notice a yellowing of the skin or eyes. These may be symptoms of hepatitis.

Progressive multifocal leukoencephalopathy (PML) is a rare brain infection that can occur with treatment with Arzerra. PML causes severe disability and can lead to death. Patients should call their doctor right away if they notice new medical problems or problems that are getting worse, such as confusion, dizziness or loss of balance, difficulty talking or walking, or strength, vision or other problems that have lasted over several days.

Tumor lysis syndrome (TLS), including the need for a hospital stay, can occur with treatment with Arzerra. TLS is caused by the fast breakdown of cancer cells, which then release their contents into the blood. This may lead to serious problems, including kidney failure or an abnormal heartbeat. Doctors may do a blood test to check their patients for TLS and may give medicines before starting treatment with Arzerra to help prevent TLS.

Arzerra can cause low blood cell counts (white blood cells, platelets, and red blood cells). These low blood cell counts can be severe and, in some cases, lead to death. Low white blood cells counts (neutropenia), can happen during treatment. Neutropenia can occur 42 days or longer after the end of treatment with Arzerra and may also last between 24 and 42 days after the last treatment dose. Doctors should regularly check their patient’s blood to see if they have low blood cell counts. Patients should call their doctor right away if they have any bleeding, bruising, red or purple spots on their skin, paleness, worsening weakness, tiredness, cough that will not go away, fever, chills, congestion, or any flu-like symptoms while receiving Arzerra.

After a patient receives Arzerra, they should not receive live vaccines until the doctor who prescribed Arzerra has told them that they may do so.

The most common side effects with Arzerra include infusion reactions, feeling tired, low white blood cell count, shortness of breath, pneumonia, rash, fever, nausea, cough, bronchitis, diarrhea, upper respiratory tract infection and low red blood cell count.

Treatment with Arzerra can increase patients’ chances for getting infections. Some infections, such as pneumonia, bronchitis, and sepsis (a blood infection), can be serious, and in some cases, life-threatening. Patients should call their doctor right away if they have a cough that will not go away, fever, chills, congestion, or any flu-like symptoms while receiving Arzerra. These symptoms may be signs of a serious infection.
Please see full Prescribing Information, including Boxed WARNING, for Arzerra (ofatumumab).

Merrimack Pharmaceuticals and Baxter BioScience Announce Completion of New Drug Application Submission to U.S. FDA for MM-398 as a Treatment for Post-Gemcitabine Metastatic Pancreatic Cancer

On April 27, 2015 Merrimack Pharmaceuticals and Baxter International reported that Merrimack has completed the rolling submission of the New Drug Application (NDA) for MM-398 (irinotecan liposome injection), also known as "nal-IRI," to the U.S. Food and Drug Administration (FDA) (Press release, Merrimack, APR 27, 2015, View Source [SID:1234503191]). Merrimack is seeking U.S. marketing approval of MM-398 for the treatment of patients with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine-based therapy. The companies also announced that Merrimack has requested priority review of the MM-398 NDA by the FDA.

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"The submission of Merrimack’s first ever NDA with the U.S. FDA is a major milestone in the company’s history and a significant step forward in our commitment to delivering new treatment options to cancer patients," said Robert Mulroy, President and CEO at Merrimack. "We are encouraged by the FDA’s support in the process and look forward to working with them throughout the NDA review."

Merrimack’s application is based upon the results of an international Phase 3 study (NAPOLI-1) conducted in patients with metastatic pancreatic cancer who previously received gemcitabine-based therapy. MM-398 in combination with 5-fluorouracil (5-FU) and leucovorin achieved its primary and secondary endpoints by demonstrating a statistically significant improvement in overall survival, progression free survival and overall response rate compared to the control group of patients who received a combination of 5-FU and leucovorin. The most common Grade 3 or higher adverse events in patients receiving MM-398 and 5-FU/LV were neutropenia, fatigue and gastrointestinal effects. This was the first global Phase 3 study in a post-gemcitabine setting to show a survival benefit in this aggressive disease. The data were previously presented in June 2014.

"This is an important achievement in our MM-398 collaboration and in our collective efforts to introduce a potentially valuable new standard of care treatment for patients with pancreatic cancer," said David Meek, head of Oncology at Baxter BioScience. "We intend to maintain this positive momentum as we prepare for the European submission in the coming months, with additional global submissions to follow shortly thereafter."

The FDA and European Medicines Agency have granted MM-398 orphan drug designation for patients with metastatic pancreatic cancer. MM-398 was granted Fast Track designation by the FDA in November 2014.

Merrimack and Baxter International’s biopharmaceutical business (NYSE: BAX) entered into an exclusive licensing agreement to develop and commercialize MM-398 outside of the United States. PharmaEngine, Inc. (Taipei, Taiwan) holds the rights to commercialize MM-398 in Taiwan.

About MM-398

MM-398 (irinotecan liposome injection), also known as "nal-IRI," is a novel encapsulation of irinotecan in a long-circulating nanoliposomal formulation. The activated form of irinotecan is SN-38, which functions by inhibiting topoisomerase I (an essential enzyme involved in DNA transcription and replication) and promoting cell death.

About Pancreatic Cancer 1,2

Pancreatic cancer is rare and deadly, accounting for only three percent of all cancer cases worldwide but is the fourth leading cause of cancer death. An estimated 140,000 new cases are diagnosed every year around the world, two-thirds of which are among people aged 65 or older.

Because the signs and symptoms of pancreatic cancer are non-specific and may not appear until the disease has spread to other sites, approximately 80% of patients are diagnosed with late stage disease. These patients are not candidates for surgery, instead receiving chemotherapy as the mainstay of their therapy. This contributes to the five year survival rate for all patients being less than six percent; fewer than 20 percent of newly diagnosed patients survive more than two years. There is no consensus on the standard of care for patients with metastatic pancreatic cancer previously treated with a gemcitabine-based therapy.

OncoGenex Regains Rights to Custirsen from Teva

On April 27, 2015 OncoGenex Pharmaceuticals reported that its wholly owned subsidiary, OncoGenex Technologies Inc., executed a termination agreement with Teva under which OncoGenex will regain rights to custirsen, an investigational compound currently in Phase 3 clinical development as a treatment for prostate and lung cancers. This transfer of rights occurs in connection with the termination of the 2009 collaboration agreement between OncoGenex and Teva (Press release, OncoGenex Pharmaceuticals, APR 27, 2015, View Source [SID:1234503186]).

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"OncoGenex is excited to move forward with the clinical investigation of custirsen in patients with advanced cancers who desperately need new treatment options," said Scott Cormack, President and CEO of OncoGenex. "The finalization of this agreement gives OncoGenex control of custirsen’s development, including the ability to move forward with plans to modify the ENSPIRIT trial design and statistical analysis plan to enable the trial to continue with fewer patients, increased confidence in success and shorter time to regulatory submission."

The agreement between the two parties to terminate the collaboration includes a $23.2 million payment from Teva.

This payment reflects a $27 million advance reimbursement amount less $0.8 million for expenses incurred by Teva in 2015 prior to the termination date as well as a $3 million holdback amount that may be used to settle additional expenses incurred by Teva related to the continued development of custirsen as well as certain indemnity claims. One half of the then remaining balance of the holdback amount will be released to OncoGenex in October 2015 with a further half of the then remaining amount paid in January 2016. Any final remaining amount will be released in April 2016.

In addition, OncoGenex will take over responsibility for all custirsen expenses, including those related to the ENSPIRIT trial, as well as manufacturing and regulatory activities for custirsen programs that were previously managed by Teva.

The company recently reported that as of December 31, 2014, it had $47.1 million in cash, cash equivalents and short-term investments, excluding the advance reimbursement payment from Teva. OncoGenex expects that the $23.2 million payment from Teva and the Company’s current resources should enable the completion of the AFFINITY trial through data readout in late 2015 or early 2016, allow for the continuation of the ENSPIRIT trial through the second interim futility analysis expected in mid-2015, and facilitate the achievement of key apatorsen clinical milestones, such as the completion of patient enrollment in the Borealis-2 trial and final data from the Spruce and Rainier clinical trials.

Additional terms of the agreement with Teva can be found in the Company’s Current Report on Form 8-K filed today and available at View Source