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FDA Approves Jakafi (ruxolitinib) for the Treatment of Patients with Uncontrolled Polycythemia Vera

On December 4, 2014 Incyte reported that the U.S. Food and Drug Administration (FDA) has approved Jakafi (ruxolitinib) for the treatment of patients with polycythemia vera (PV) who have had an inadequate response to or are intolerant of hydroxyurea (Press release Incyte, DEC 4, 2014, View Source [SID:1234501068]). Jakafi, an oral medication, is the first and only product approved by the FDA for PV, a rare and progressive blood cancer.

“The approval of Jakafi represents an important advance for patients with uncontrolled PV. For the first time we are able to provide these patients a treatment that has been shown to provide effective and consistent control of their blood counts and reduce spleen volume,” said Srdan Verstovsek, M.D., Ph.D., Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center.

PV is a myeloproliferative neoplasm (MPN) and is typically characterized by elevated hematocrit, the volume percentage of red blood cells in whole blood, which can lead to a thickening of the blood and an increased risk of blood clots, as well as an elevated white blood cell and platelet count1. PV may occur at any age but often presents later in life, with a median age at diagnosis of 60 years.

Approximately 100,000 patients in the U.S. are living with PV3. Current standard treatment for PV is phlebotomy (the removal of blood from the body) plus aspirin. When phlebotomy can no longer control PV, chemotherapy such as hydroxyurea, or interferon, is utilized4,5. Approximately one in four (~25,000) patients with PV are considered uncontrolled6,7 because they have an inadequate response to or are intolerant of hydroxyurea, the most commonly used chemotherapeutic agent for the treatment of PV.

Patients with PV who fail to consistently maintain appropriate blood count levels, including appropriate hematocrit levels, have an approximately four times higher risk of major thrombosis (blood clots) or cardiovascular death8. Patients with PV can also suffer from an enlarged spleen, and a significant symptom burden which may be attributed to thickening of the blood and a lack of oxygen to parts of the body9. These symptoms commonly include fatigue, itching, night sweats, bone pain, fever, and weight loss5.

“Being diagnosed with a serious disease affects a person in a way that cannot be predicted,” said Robert Rosen, a patient living with PV and Founder and Chairman of the MPN Research Foundation. “The FDA approval of this drug is good news for our community and provides a new treatment option for those patients who do not respond to other therapies. This news confirms the ongoing importance of continued research, and the critical role that the MPN Research Foundation plays in improving the lives of patients.”

Jakafi is also the first and only FDA-approved product for the treatment of intermediate or high-risk myelofibrosis, a closely related blood cancer. Jakafi is a JAK1 and JAK2 inhibitor that targets overactive JAK pathway signaling, which plays a critical role in the development of both myelofibrosis and polycythemia vera10.

“The team at Incyte is proud that a second indication has been approved for Jakafi, further confirming the strength of our science and our commitment to discovering and developing innovative treatments for patients with cancer,” said Hervé Hoppenot, Incyte’s President and Chief Executive Officer.

The approval of Jakafi for the treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea was based on data from the pivotal Phase III RESPONSE trial, which was conducted under a Special Protocol Assessment from the FDA. In this trial, patients treated with Jakafi demonstrated superior hematocrit control and reductions in spleen volume compared to best available therapy. In addition, a greater proportion of patients on the ruxolitinib treatment arm achieved complete hematologic remission – which was defined as achieving hematocrit control, and lowering platelet and white blood cell counts. In the RESPONSE trial, the most common hematologic adverse reactions (incidence > 20%) were thrombocytopenia and anemia. The most common non-hematologic adverse events (incidence >10%) were headache, abdominal pain, diarrhea, dizziness, fatigue, pruritus, dyspnea and muscle spasms.

FDA Approves BLINCYTO™ (Blinatumomab) Immunotherapy for the Treatment of Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia

On December 3, 2014 Amgen reported that the U.S. Food and Drug Administration (FDA) has granted approval of BLINCYTO (blinatumomab) for the treatment of patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) (Press release Amgen, DEC 3, 2014, View Source;p=RssLanding&cat=news&id=1994704 [SID:1234501069]). This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials. With this approval, BLINCYTO becomes the first FDA-approved bispecific CD19-directed CD3 T-cell engager (BiTE) antibody construct product, and the first single-agent immunotherapy to be approved for the treatment of patients with Ph- relapsed or refractory B-cell precursor ALL, a rare and rapidly progressing cancer of the blood and bone marrow.1-3

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"The FDA’s breakthrough therapy designation and accelerated approval of BLINCYTO underscores the critical need for new treatment options for patients with relapsed or refractory B-cell precursor ALL, who are often young adults," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "BLINCYTO is the first clinical and regulatory validation of the BiTE platform, a new and innovative approach that helps the body’s own immune system fight cancer."

The BLINCYTO approval is based on results of Amgen’s ‘211 trial, a Phase 2, multicenter, single-arm open-label study. Eligible patients were > 18 years of age with Ph- relapsed or refractory B-cell precursor ALL. Relapsed or refractory was defined as relapsed with first remission duration of < 12 months in the first salvage, or relapsed or refractory after first salvage therapy, or relapsed within 12 months of allogeneic hematopoietic stem cell transplantation (HSCT), and had > 10 percent blasts in bone marrow. Of the 185 patients evaluated in the trial, 41.6 percent (77/185; 95 percent CI: 34.4-49.1) achieved complete remission or complete remission with partial hematologic recovery (CR/CRh*) within two cycles of treatment with BLINCYTO, which was the primary endpoint of the study. The majority of responses (81 percent [62/77]) occurred within the first cycle of treatment. Among patients who achieved CR/CRh*, 39 percent (30/77) went on to HSCT, and 75.3 percent (58/77 95 percent CI: 64.2-84.4) achieved minimal residual disease (MRD) response, a measure of eradication of residual disease at the molecular level.

"The approval of BLINCYTO represents a significant milestone in immunotherapy research, providing clinicians the opportunity to offer a new single-agent therapy to patients fighting this highly aggressive cancer with previously limited options," said Anthony S. Stein, M.D., clinical professor, Hematology/Oncology at City of Hope.

Array To Regain Worldwide Rights To Binimetinib

On December 3, 2014 Array BioPharma reported that it has reached a definitive agreement with Novartis International Pharmaceutical Ltd. to regain full worldwide rights to binimetinib, a MEK inhibitor in three Phase 3 trials (Press release Array BioPharma, DEC 3, 2014, View Source;p=RssLanding&cat=news&id=1994724 [SID:1234501062]). This agreement is conditional on the closing of transactions announced by Novartis and GlaxoSmithKline PLC (GSK) on April 22, 2014, which are expected in the first half of 2015, and remain subject to regulatory approval. Array had previously granted Novartis worldwide exclusive rights to develop and commercialize binimetinib under a 2010 License Agreement, which will terminate and be superseded by a new set of agreements between the parties.

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"Regaining full worldwide rights to binimetinib, an innovative late-stage oncology product, represents a tremendous opportunity for Array," said Ron Squarer, Chief Executive Officer, Array BioPharma. "Binimetinib is currently advancing in three Phase 3 clinical trials and, we expect to file for our first regulatory approval during the first half of 2016. With this agreement, we are in a strong position to successfully develop and commercialize binimetinib to the benefit of cancer patients."

Novartis stated, "Binimetinib has demonstrated promising results for cancer patients across several different clinical trials. We are committed to supporting a successful transition to Array."

Upon deal close, Array will receive up to $85 million and Novartis’ global, exclusive license to binimetinib will terminate with all rights reverting to Array. Novartis has agreed to provide transitional regulatory, clinical development and manufacturing services as specified below and will assign to Array patent and other intellectual property rights it owns to the extent relating to binimetinib. All clinical trials involving binimetinib, including the COLUMBUS, NEMO and MILO pivotal trials, will continue to be conducted as currently contemplated.

Novartis will be responsible for continued conduct and funding of the COLUMBUS trial. This obligation will transfer to any future owner of LGX818 (encorafenib). Following deal close, Novartis will reimburse Array for all remaining out-of-pocket expenses and half of all remaining fully-burdened full time equivalent (FTE) costs associated with MILO, which Array will continue to conduct. For NEMO and all other ongoing and planned clinical trials, Novartis will conduct and solely fund each trial, until a mutually agreed-upon transition date to Array. Following this transition, Novartis will reimburse Array for all remaining out-of-pocket expenses and half of all remaining fully-burdened FTE costs required to complete these studies.

Novartis will remain responsible for conducting and funding development of the NRAS melanoma companion diagnostic until Premarket Approval is received from the U.S. Food and Drug Administration. Following approval, Novartis will transfer the product and Premarket Approval to a diagnostic vendor of Array’s designation.

Novartis also retains binimetinib supply obligations for all clinical and commercial needs for up to 30 months after closing and will also assist Array in the technology and manufacturing transfer of binimetinib. Novartis will also provide Array continued access to several Novartis pipeline compounds including, but not limited to, LEE011 (CDK 4/6 inhibitor) and BYL719 (a-PI3K inhibitor), for use in currently ongoing combination studies, and possible future studies, including Phase 3 trials, with binimetinib.

Oncolytics Biotech® Inc. Announces Filing for Orphan Drug Designation with the U.S. FDA for Pancreatic and Ovarian Cancers

On December 2, 2014 Oncolytics Biotech reported that it has submitted applications for Orphan Drug Designation to the U.S. Food and Drug Administration ("FDA") for REOLYSIN for the treatment of pancreatic and ovarian cancers (Press release Oncolytics Biotech, DEC 2, 2014, View Source [SID:1234501052]).

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The FDA grants Orphan Drug Designation status to products that treat rare diseases, providing incentives to sponsors developing drugs or biologics. The FDA defines rare diseases as those affecting fewer than 200,000 people in the United States at any given time. Orphan Drug Designation provides the sponsor certain benefits and incentives, including a period of marketing exclusivity if regulatory approval is ultimately received for the designated indication, potential tax credits for certain activities, eligibility for orphan drug grants, and the waiver of certain administrative fees. The receipt of Orphan Drug Designation status does not change the regulatory requirements or process for obtaining marketing approval. For more information, please visit:
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REOLYSIN is Oncolytics’ proprietary isolate of the reovirus. Its primary mode of activity is to infect and selectively target tumours with activating Ras pathway mutations and/or over-expressions of Ras pathway elements including, amongst others, EGFR, BRAF, and KRAS. Up to 70% of pancreatic cancers have activating Ras pathway mutations and/or over-expressions.

"Many patients with either pancreatic or ovarian cancer are not diagnosed until after their disease has progressed to its later stages, which reduces their survival outcomes," said Dr. Brad Thompson, President and CEO of Oncolytics. "The development of more targeted treatment options, in this case an agent targeting cancers with Ras pathway defects, will allow patients to access the most suitable treatment for their specific case."

TESARO and AnaptysBio Expand Immuno-Oncology Collaboration to Include Novel Bispecific Antibody Candidate

On December 2, 2014 TESARO and AnaptysBio reported an expansion of their immuno-oncology collaboration and exclusive license agreement to include development of a novel bispecific antibody candidate designed to target two undisclosed immune checkpoints (Press release TESARO, DEC 2, 2014, View Source [SID:1234501050]).

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AnaptysBio and TESARO first initiated their collaboration in March of 2014, and have together focused on the development of monospecific antibody drug candidates targeting TIM-3, LAG-3 and PD-1 and dual reactive antibody drug candidates targeting PD-1/TIM-3 and PD-1/LAG-3. Since the beginning of this partnership, Investigational New Drug (IND) enabling preclinical studies of TSR-042 (anti-PD-1 antibody candidate) have been initiated, and additional clinical candidates have been identified, including lead candidates targeting TIM-3 and LAG-3.

"Through our collaboration with AnaptysBio, we are employing a variety of approaches, including monospecific, bispecific and dual specific antibodies, to address some of the most validated and promising immune checkpoint targets," said Mary Lynne Hedley, Ph.D., president and COO of TESARO. "We are committed to advancing the science of immuno-oncology in order to potentially transform the care of patients with cancer. Our team looks forward to continued collaboration with AnaptysBio on these programs and to the presentation of data describing our anti-TIM-3 antibody candidate at the AACR (Free AACR Whitepaper) conference later today in Orlando."

"AnaptysBio continues to focus on the development of therapeutic antibodies for unmet medical needs in immuno-oncology, inflammation and fibrosis. Our strategic advantage is the ability to rapidly discover and develop therapeutic antibodies against emerging biological targets using the natural somatic hypermutation mechanism encoded within the human immune system," said Hamza Suria, president and CEO of AnaptysBio. "We are pleased to expand our collaboration with TESARO, and look forward to advancing multiple immuno-oncology antibodies into the clinic."

Under the terms of this expansion, TESARO will pay AnaptysBio an undisclosed upfront fee and will provide funding for all costs incurred by AnaptysBio related to the development of a clinical antibody candidate. For each program within the collaboration, AnaptysBio is eligible to receive milestone payments if certain research and development events are achieved and additional payments for achievement of certain U.S. and ex-U.S. regulatory submissions and approvals in multiple indications. AnaptysBio will also be eligible to receive royalties related to worldwide net sales of products developed under the collaboration, and may earn certain commercial milestone payments if specified levels of annual worldwide net sales are attained. AnaptysBio and TESARO will together complete preclinical development of the antibody candidates, with TESARO being solely responsible for all clinical development, manufacturing, regulatory and commercial activities.