On November 23, 2015 The U.S. Food and Drug Administration reported that it approved Opdivo (nivolumab) to treat patients with advanced (metastatic) renal cell carcinoma, a form of kidney cancer, who have received a certain type of prior therapy.
"Opdivo provides an important therapy option for patients with renal cell carcinoma," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research (Press release, , NOV 23, 2015, View Source [SID:1234508328]). "It is one of few therapies that have demonstrated the ability to extend patients’ survival in treating this disease." Torisel (temsirolimus), approved in 2007, is the only other FDA-approved therapy that has demonstrated overall survival in renal cell cancer.

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Renal cell carcinoma is the most common form of kidney cancer in adults and forms in the tissues of the kidney that make urine. The National Cancer Institute estimates 61,560 new cases and 14,080 deaths from kidney and renal pelvis cancer in the United States this year.

"Additionally, Opdivo’s extended indication, from melanoma and non-small cell lung cancer to renal cell cancer, demonstrates how immune therapies can benefit patients across a wide range of tumors," continued Dr. Pazdur.

Opdivo works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). By blocking this pathway, Opdivo may help the body’s immune system fight cancer cells. Opdivo is intended for use in renal cell carcinoma in patients who have received prior anti-angiogenic therapy (treatments that interfere with the blood vessels that contribute to the growth of cancerous cells).

The safety and efficacy of Opdivo for this use were demonstrated in an open-label, randomized study of 821 patients with advanced renal cell carcinoma whose disease worsened during or after treatment with an anti-angiogenic agent. Patients were treated with Opdivo or another type of kidney cancer treatment called everolimus (marketed as Afinitor). Those treated with Opdivo lived an average of 25 months after starting treatment compared to 19.6 months in those treated with Afinitor. This effect was observed regardless of the PD-L1 expression level of patients’ renal cell tumors. Additionally, 21.5 percent of those treated with Opdivo experienced a complete or partial shrinkage of their tumors, which lasted an average of 23 months, compared to 3.9 percent of those taking Afinitor, lasting an average of 13.7 months.

The most common side effects of Opdivo for this use are conditions relating to abnormal weakness or lack of energy (asthenic conditions), cough, nausea, rash, difficulty breathing (dyspnea), diarrhea, constipation, decreased appetite, back pain and joint pain (arthralgia).

Opdivo also has the potential to cause serious side effects that result from the immune system effect of Opdivo (known as "immune-mediated side effects"). These severe immune-mediated side effects involve healthy organs, including the lung, colon, liver, kidneys, hormone-producing glands and the brain.

The FDA granted the Opdivo application a breakthrough therapy designation, fast track designation, and priority review status. These are distinct programs intended to facilitate and expedite the development and review of certain new drugs in light of their potential to benefit patients with serious or life-threatening conditions.

Opdivo is marketed by Bristol-Myers Squibb based in Princeton, New Jersey. Torisel is marketed by Pfizer, based in New York, New York. Afinitor is marketed by Novartis Pharmaceuticals of East Hanover, New Jersey.

On November 24, 2015 CTI BioPharma Corp. (CTI BioPharma or the Company) (NASDAQ and MTA: CTIC) reported that the United Kingdom’s National Cancer Research Institute (NCRI) Haematological Oncology Clinical Studies Group has chosen to advance tosedostat, the Company’s investigative oral aminopeptidase inhibitor, to the second stage of a randomized clinical trial of low-dose cytarabine plus or minus tosedostat in older patients with Acute Myeloid Leukemia (AML) or high risk Myelodysplastic Syndrome (MDS) (Press release, CTI BioPharma, NOV 23, 2015, View Source;p=RssLanding&cat=news&id=2116992 [SID:1234508332]). The AML Less Intensive (LI-1) trial is designed as a "Pick-a-Winner" trial to be able to simultaneously test a number of promising agents added to standard therapy with low-dose cytarabine in older patients with AML or MDS who are unfit for standard aggressive induction therapy. Nine regimens have been tested in the Pick-a-Winner program, of which only 4, including tosedostat, have passed the initial hurdle for progression (which requires evidence of an improvement in remission rate with acceptable safety). The ultimate aim of the trial is to identify treatments that can double the 2-year survival of patients in this group. Based on the randomized Phase 2 interim analysis, the trial management group determined that tosedostat should proceed to the next stage of the study. It is anticipated that an additional 110 patients will be required in such phase. A further evaluation will take place before the intended expansion to a 400 patient Phase 3 trial.

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Tosedostat is a potential first-in-class selective inhibitor of aminopeptidases, which are enzymes required by some tumor cells, but not normal cells, to provide a source of amino acids necessary for growth and tumor cell survival.

"A large portion of older patients and patients with comorbid conditions are poorly suited for conventional intensive chemotherapy due to a high rate of treatment-related mortality. For these patients, there is a significant unmet need for effective and well tolerated alternative therapies," said Jack Singer, M.D., Chief Scientific Officer of CTI BioPharma. "We are pleased that tosedostat has been selected to continue in this trial and is moving forward to the next stage. Tosedostat has demonstrated encouraging clinical activity in three prior Phase 2 studies in both first-line AML in older patients and in patients who relapsed following standard therapies. Tosedostat is an oral agent given once daily on an outpatient basis that has not been associated with drug-related blood count suppression."

About the LI-1 Trial
In this Phase 2/3 trial, referred to as the AML Less Intensive (LI-1) trial, patients are randomized to standard treatment with low dose cytarabine, versus several investigational treatments – each usually in combination with low dose cytarabine. This is called a "Pick-a-Winner" trial design. Under this design, the Phase 2 portion of the trial initially randomized 50 patients per arm, and, if the complete response rate of cytarabine plus novel therapy appeared satisfactory, the randomization continues to the next stage usually with an additional 50 patients per arm. There is then a further assessment by the data monitoring committee to allow the trial to continue to the final stage in which case up to a total of approximately 200 patients per arm would be enrolled. Overall survival will serve as the primary endpoint of the trial. The NCRI Haematological Oncology Clinical Studies Group under the sponsorship of Cardiff University is conducting the trial.

About Tosedostat
Tosedostat is an oral aminopeptidase inhibitor that has demonstrated anti-tumor responses in blood-related cancers and solid tumors in Phase 1-2 clinical trials. Tosedostat is currently being evaluated in multiple Phase 2 clinical trials for the treatment of patients with AML or high-risk MDS. Tosedostat is not approved or commercially available.

About Acute Myeloid Leukemia and Myelodysplastic Syndrome
AML is the most common acute leukemia affecting adults, and its incidence increases with age. In older patients, AML may occur de novo or secondary to prior anti-cancer therapy, or from progression of other diseases, such as myelodysplasia. AML is a cancer characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute leukemia affecting adults, and its incidence increases with age.1 The symptoms of AML are caused by the replacement of normal bone marrow with leukemic cells, which causes a drop in red blood cells, platelets, and normal white blood cells, leading to infections and bleeding. AML progresses rapidly and is typically fatal within weeks or months if left untreated. In 2015, approximately 20,830 new cases of AML are expected to be diagnosed in the United States and an estimated 10,460 are expected to die from the disease.2 While AML may occur at any age, adults at least 60 years of age are more likely than younger people to develop the disease.2 Although a substantial proportion of younger individuals who develop AML can be cured, AML in the elderly typically responds poorly to standard therapy with few complete remissions.

AML may develop from the progression of other diseases, such as MDS. MDS are a group of diverse bone marrow disorders in which the bone marrow does not produce enough healthy blood cells. MDS is often referred to as a "bone marrow failure disorder."

On November 23, 2015 Genmab A/S (OMX: GEN) reported that the Phase III study of single agent ofatumumab compared to single agent rituximab in patients with follicular non-Hodgkin’s lymphoma (NHL) that has relapsed at least 6 months after completion of treatment with a rituximab-containing regimen will be stopped early (Press release, Genmab, NOV 23, 2015, View Source [SID:1234508333]). The decision to stop the study was made after a planned interim analysis performed by an Independent Data Monitoring Committee (IDMC) showed that it was unlikely that ofatumumab would show superiority if the trial was to be completed as planned.

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"The outcome of the interim analysis in this study is disappointing as we had hoped to see superiority of ofatumumab. The data from the study will now be prepared so that it can be presented at a future scientific conference," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

Today’s news does not impact any other ongoing studies with ofatumumab.

About the study
This Phase III study aimed to randomize up to 516 patients to receive ofatumumab (1000 mg) or rituximab (375 mg/m2) by intravenous infusion for four weekly doses. Patients who had stable or responsive disease then received single infusions of ofatumumab or rituximab every two months for four additional doses for a total of eight doses over nine months. The primary endpoint of the study was progression free survival.

About Ofatumumab (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. 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 not approved anywhere in the world as treatment for relapsed follicular NHL.

Please see full Prescribing Information, including Boxed WARNING for Arzerra (ofatumumab).

Arzerra is marketed under a collaboration agreement between Genmab and Novartis.

On November 23, 2015 CTI BioPharma Corp. (CTI BioPharma) (NASDAQ and MTA: CTIC) reported findings from an investigator-sponsored preclinical study showing the potential synergistic effect of combining pacritinib, an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R, with an epidermal growth factor receptor (EGFR) inhibitor in decreasing brain tumor initiating cells (BTIC) viability (Press release, CTI BioPharma, NOV 22, 2015, View Source;p=RssLanding&cat=news&id=2114521 [SID:1234508311]). BTICs have cancer stem cell characteristics and are believed to be responsible for disease initiation and recurrence. Additionally, high rates of mutations in BTICs may lead to the rapid emergence of resistance in GBM, the most common and aggressive primary brain cancer. Given that upregulation of the JAK/STAT pathway may be a common mechanism of resistance to EGFR antagonists, the current study demonstrates the potential for combination therapies with pacritinib to be a promising therapeutic avenue in GBM. The early phase findings also showed prolonged survival in an intracerebral BTIC xenograft preclinical model of human GBM when delivered in combination with temozolomide.

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These findings were presented by Ms Katharine Jensen from the laboratory of Drs Artee Luchman and Samuel Weiss, at the Hotchkiss Brain Institute, University of Calgary in an oral presentation (abstract #ATPS-52) during the 20th Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology (SNO) held November 19-22, 2015 in San Antonio, Texas.

"Although activating mutations in EGFR are common in GBM, physiological challenges with drug penetration, drug pharmacokinetics and rapid emergence of resistance have resulted in EGFR inhibitors showing limited effectiveness as monotherapies," said Dr. Weiss, Professor at the University of Calgary’s Cumming School of Medicine and Director of the Hotchkiss Brain Institute. "Our findings support the hypothesis that combination therapy, for example targeting both the JAK/STAT pathways inhibited by pacritinib and EGFR, may improve clinical outcomes for patients with GBM."

"The tolerability profile of pacritinib observed in the clinic to date, along with the ability to achieve meaningful intracerebral levels in preclinical models, makes it a candidate to be explored for use in combination therapy for GBM," said Jack W. Singer, M.D., Chief Scientific Officer and Global Head of Translational Medicine at CTI BioPharma. "We believe these findings further support the potential for clinical trials of pacritinib in difficult to treat, non-hematological cancers."

The combination of pacritinib with one of three different EGFR inhibitors (afatinib, lapatinib, erlotinib) each resulted in decreased BTIC viability. Additionally, the effect of combining pacritinib with afatinib was shown to be synergistic in BTIC growth inhibition. Ongoing investigations are focusing on whether combinatorial therapy can improve survival in a preclinical model.

About Pacritinib

Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. In August 2014, pacritinib was granted Fast Track designation by the FDA for the treatment of intermediate and high risk myelofibrosis, including but not limited to patients with disease-related thrombocytopenia, patients experiencing treatment-emergent thrombocytopenia on other JAK2 inhibitor therapy, or patients who are intolerant of, or whose symptoms are sub-optimally managed on other JAK2 inhibitor therapy. The FDA’s Fast Track process is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Pacritinib does not have regulatory approval and is not commercially available.

CTI BioPharma and Baxalta Incorporated (NYSE:BXLT) are parties to a worldwide license agreement to develop and commercialize pacritinib. CTI BioPharma and Baxalta will jointly commercialize pacritinib in the U.S. while Baxalta has exclusive commercialization rights for all indications outside the U.S.

About Glioblastoma Multiforme

According to the National Cancer Institute, GBM is the most common and deadliest type of primary brain tumor in adults. GBM has an incidence of two to three per 100,000 adults per year, and accounts for 52 percent of all primary brain tumors.1 The current standard of care for patients with GBM is a surgical resection, if possible, followed by radiation given with concurrent temozolomide. The prognosis for the majority of patients with GBM is poor with median survival of approximately 14.6 months with less than 30 percent of patients surviving two years using current therapies.2

On November 23, 2015 CTI BioPharma Corp. (CTI BioPharma) (NASDAQ and MTA: CTIC) reported the initiation of its rolling new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for pacritinib, an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R (Press release, CTI BioPharma, NOV 22, 2015, View Source;p=RssLanding&cat=news&id=2114525 [SID:1234508312]). As part of the application, CTI BioPharma and its partner, Baxalta Incorporated (Baxalta), are seeking accelerated approval and priority review for pacritinib for the treatment of patients with intermediate and high-risk myelofibrosis with low platelet counts of less than 50,000 per microliter (<50,000/uL). If approved for the requested indication, pacritinib would be the first JAK2 inhibitor approved for the treatment of patients with myelofibrosis with platelet counts of less than 50,000/uL – a specific patient population for which there are currently no approved drugs. The rolling NDA allows completed portions of an NDA to be submitted and reviewed by the FDA on an ongoing basis. CTI BioPharma and Baxalta plan to complete the submission before the end of 2015.

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Myelofibrosis (a type of myeloproliferative neoplasm) is a rare, but serious and life-threatening chronic bone marrow disorder caused by the accumulation of malignant bone marrow cells that triggers an inflammatory response and scars the bone marrow. Myelofibrosis is associated with significantly reduced quality of life and shortened survival, can affect patients of all ages (with a median affected age being 65 years) and an estimated prevalence in the United States of approximately 18,000 patients.

"We believe the initiation of the rolling NDA submission represents a major step forward toward potentially offering pacritinib as a next generation JAK2/FLT3 inhibitor to patients with this rare and chronic type of blood cancer," said James A. Bianco, M.D., President and CEO of CTI BioPharma. "We are excited to have achieved this milestone and look forward to working with the FDA during the review process, with the goal of bringing this important treatment to market – which we hope will fill an unmet need for many patients whose lives are profoundly impacted by myelofibrosis."

The submission includes data from the PERSIST-1 Phase 3 trial – as well as data from Phase 1 and 2 studies of pacritinib. Submission of an NDA after a single Phase 3 trial under accelerated approval, instead of waiting to complete two Phase 3 trials, could potentially reduce time to market by up to 14 months. In August 2014, pacritinib was granted Fast Track designation by the FDA for the treatment of intermediate and high-risk myelofibrosis including, but not limited to, patients with disease-related thrombocytopenia (low platelet counts); patients experiencing treatment emergent thrombocytopenia on another JAK2 therapy; or patients who are intolerant to or whose symptoms are not well controlled (or sub-optimally managed) on another JAK2 therapy.

About Myelofibrosis and Myeloproliferative Neoplasms
Myelofibrosis is a one of three main types of myeloproliferative neoplasms (MPN), which are a closely related group of hematological blood cancers. The three main types of MPNs are myelofibrosis, polycethemia vera, and essential thrombocythemia.1 Myelofibrosis is a serious and life-threatening chronic bone marrow disorder caused by the accumulation of malignant bone marrow cells that triggers an inflammatory response and scars the bone marrow. The replacement of bone marrow with scar tissue limits its ability to produce red blood cells, prompting the spleen and liver to take over this function. Symptoms that arise from this disease include enlargement of the spleen, anemia, extreme fatigue, and pain.

The estimated prevalence of MPNs suggest there are approximately 300,000 people living with the disease in the U.S. of which myelofibrosis accounts for approximately 18,000 patients.2 In Europe, there is a wide variation of prevalence observed across data sources. Myelofibrosis has a median age of 64 at the time of diagnosis2 and is a progressive disease with approximately 20 percent of patients eventually developing acute myeloid leukemia.3 The median survival for high-risk patients is less than one and a half years; median survival for myelofibrosis patients overall is approximately six years.4

About Pacritinib
Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. In August 2014, pacritinib was granted Fast Track designation by the FDA for the treatment of intermediate and high risk myelofibrosis, including but not limited to patients with disease-related thrombocytopenia, patients experiencing treatment-emergent thrombocytopenia on other JAK2 inhibitor therapy, or patients who are intolerant of, or whose symptoms are sub-optimally managed on other JAK2 inhibitor therapy. The FDA’s Fast Track process is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Pacritinib does not have regulatory approval and is not commercially available.

CTI BioPharma and Baxalta (NYSE:BXLT) are parties to a worldwide license agreement to develop and commercialize pacritinib. CTI BioPharma and Baxalta will jointly commercialize pacritinib in the U.S. while Baxalta has exclusive commercialization rights for all indications outside the U.S.