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FDA Expands Approval of Velcade for Patients with Untreated Mantle Cell Lymphoma


Millennium, a Cambridge subsidiary of the Japanese drugmaker Takeda Pharmaceuticals International, said that US health regulators have expanded approval of Velcade for a rare form of blood cancer.

The US Food and Drug Administration (FDA) approved Velcade (bortezomib) for injection for use in previously untreated patients with mantle cell lymphoma (MCL), a rare, aggressive type of B-cell non-Hodgkin lymphoma (NHL) that typically occurs in older adults.

Velcade was first approved in 2003 to treat multiple myeloma, and then gained additional approval in 2006 for use in patients with relapsed or refractory MCL. Now the drug becomes the first treatment available in the US approved for use in previously untreated patients with MCL.

The approval is based on results from a head-to-head Phase III study that showed that previously untreated patients receiving Velcade-containing combination (VcR-CAP) experienced a 59 percent relative improvement in the study’s primary endpoint of progression-free survival (PFS) compared to those who were administered standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) regimen. The study evaluated the safety and efficacy of VcR-CAP vs R-CHOP in 487 patients with previously untreated MCL who were ineligible or not considered for a bone marrow transplant. The complete response (CR) rate for patients receiving VcR-CAP vs. R-CHOP was 44 percent versus 34 percent, respectively.

“We are delighted Velcade has received approval in previously untreated mantle cell lymphoma. The Velcade-combination delivered an 11-month median advantage in progression-free survival as compared to a current standard of care,” said Dixie-Lee Esseltine, MD, FRCPC, Vice President, Oncology Clinical Research, Takeda Pharmaceuticals International Co. “Since 2006, Velcade has proven to be an important therapy for the treatment of relapsed or refractory mantle cell lymphoma, and it can now be used as an initial treatment for all patients with mantle cell lymphoma.”

MCL constitutes about six percent of cases of NHL. The disease typically starts in the lymph nodes, but can spread to other tissues, such as bone marrow and liver. The expected overall survival for MCL is four to five years. The five-year survival rate for patients with advanced stage MCL is approximately 50 percent.

Millennium was acquired by Takeda in 2008. The company is will soon change its name to Takeda Oncology.

Source: Takeda

Last updated: 10/10/14; 11:25am EST

Sunesis' Cancer Drug Fails its Late-Stage Study

Sunesis Pharmaceuticals

Sunesis Pharmaceuticals Inc. today announced results from its late-stage study of its experimental drug vosaroxin, saying that it failed to meet the primary endpoint.

Following the announcement, the company’s shares fell more than 70 percent.

Sunesis was studying experimental vosaroxin in patients with acute myeloid leukemia (AML). The Phase III trial, known as the VALOR trial, evaluated vosaroxin and chemotherapy drug cytarabine in patients with first relapsed or refractory AML. The late-stage study enrolled 711 patients, who were stratified for age, geography and disease status. According to Sunesis, the trial did not meet its primary endpoint of demonstrating a statistically significant improvement in overall survival (OS). The results showed that patients receiving the combination lived a median of 7.5 months compared to 6.1 months for patients receiving cytarabine and placebo.

However, since transplant may cofound the primary analysis, a predefined analysis of OS censoring for stem cell transplantation was planned. In this analysis, patients receiving the vosaroxin combination had a median OS of 6.7 months versus 5.3 months for the group receiving placebo. Additionally, the company said that the trial demonstrated a clinically significant benefit in complete remission (CR) rate, the secondary endpoint.

According to the company, participants over the age of 60 demonstrated better results than those under the age of 60. In the intent-to-treat population, the rate of serious adverse events was 55.5 percent in the vosaroxin combination compared to 35.7 percent in the placebo group.

“VALOR was a robust, well-conducted trial, among the largest in the relapsed or refractory AML setting. The study outcomes are very encouraging, and I look forward to a full presentation of the data in a peer-reviewed forum,” said Robert Stuart, MD, Professor of Medicine, Division of Hematology/Oncology, Department of Medicine, Medical University of South Carolina, an investigator of the VALOR study and chairman of the study’s steering committee. “The clinical benefit is particularly impressive in patients aged 60 years and older, a population for whom there is no therapeutic standard of care.”

The company said that based on the results of the trial, it plans to seek approval of the drug in Europe. Sunesis said it will meet with the US Food and Drug Administration (FDA) to determine the appropriate regulatory path forward. Detailed results of the clinical trial will be submitted for presentation at an upcoming medical conference.

“There remains an acute need for new treatment options in AML, particularly relapsed refractory patients, where no therapy has demonstrated a survival benefit in a pivotal Phase 3 trial in more than 40 years,” said Adam Craig, MD, PhD, Executive Vice President, Development and Chief Medical Officer of Sunesis. “While we continue to evaluate the findings of VALOR in their totality, we believe the results demonstrate a clinically meaningful and important advancement in the treatment of this disease.”

AML is a rapidly progressing cancer of the blood, characterized by the uncontrolled proliferation of immature blast cells in the bone marrow. According to estimates from the American Cancer Society (ACS), there will be approximately 18,860 new cases of AML and approximately 10,460 deaths from AML in the US in 2014. AML typically affects older adults, with a median age of patient diagnosis of about 67 years. AML patients with relapsed or refractory disease and newly diagnosed AML patients over 60 years of age with poor prognostic risk factors typically die within one year.

Source: Sunesis Pharmaceuticals Inc.

Last updated: 10/6/14; 2:00pm EST

Novartis Partners with Bristol-Myers Squibb to Test Lung Cancer Combination Therapies


Today, Novartis announced that it has partnered with Bristol-Myers Squibb Company (BMS) to test a few of its cancer drugs in combination with BMS’ PD-1 immune checkpoint inhibitor Opdivo (nivolumab).

The companies entered into a clinical collaboration agreement to evaluate the safety, tolerability and preliminary efficacy of three of Novartis’ molecularly targeted compounds in combination with BMS’ Opdivo in Phase I/II trials of patients with non-small cell lung cancer (NSCLC). Novartis will test its experimental INC280 and EGF816 and the newly-approved ALK inhibitor Zykadia with BMS’ Opdivo for a joint attack on NSCLC.

“Preclinical data suggests that combining molecularly targeted agents with immunotherapies such as nivolumab may have synergistic effects and lead to better outcomes for patients,” said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. “This collaboration enables us to study several key compounds, including our new highly-potent ALK inhibitor Zykadia, together with a promising, novel immunotherapy agent, paving the way for potential new treatment approaches for patients with NSCLC.”

Novartis will conduct both studies, one of which will evaluate the combination of Opdivo and Zykadia (ceritinib) for those with anaplastic lymphoma kinase-positive (ALK+) metastatic NSCLC who have progressed or are intolerant to Pfizer’s Xalkori (crizotinib). A second study will test Opdivo with INC280, a potent and highly selective inhibitor of c-MET receptor tyrosine kinase, and separately with EGF816, a potent, third-generation EGFR tyrosine kinase inhibitor that is active against T790 mutations.

“Combining Opdivo with select targeted agents from Novartis complements our broad global development strategy of immuno-oncology combinations across the spectrum of lung cancer settings, and supports our global of improving outcomes for patients. We look forward to working with Novartis to fully explore how the combination of these agents can potentially advance care for lung cancer patients,” said Michael Giordano, senior vice president, Oncology Development, Bristol-Myers Squibb.

Despite advancements, treatment for lung cancer remains a significant medical need, and the studies will explore the potential of enhanced anti-tumor response using a combined immunotherapy and targeted molecular approach.

Novartis said that the collaboration further advances its development efforts in the field of immunotherapy. The company acquired CoStim Pharmaceuticals Inc. earlier this year, adding late discovery stage immunotherapy programs focused on targets, including PD-1.

Sources: Bristol-Myers Squibb Company; Novartis

Last updated: 10/6/14; 11:50am EST

Committee Recommends the Continuation of Threshold's Late-Stage Sarcoma Trial

Threshold Pharmaceuticals

Threshold Pharmaceuticals, Inc. said that the Independent Data Monitoring Committee (IDMC) has recommended that its late-stage cancer trial continue as planned.

Threshold said that the IDMC has completed the planned interim efficacy and safety analyses of unblinded data from its pivotal Phase III clinical trial of TH-302 in combination with doxorubicin versus doxorubicin alone in patients with locally advanced unresectable or metastatic soft tissue sarcoma (STS). Based on their findings, the committee recommended that the trial continue as planned to its natural conclusion.

Threshold and its partner Merck KGaA, have been and will remain blinded to the data from the trial. Based on projections derived from the interim analysis, Threshold is revising its guidance on timing for the number of events (deaths) required for the primary efficacy analysis. The company previously projected that 434 deaths would occur around the middle of 2015. However, the revised projections suggest the requisite events will occur in the latter half of 2015.

“The IDMC’s recommendation to continue the trial is in line with our expectations and previous guidance that this was the likely outcome in light of the very high statistical hurdle for demonstrating efficacy in the interim analyses,” said Barry Selick, PhD, Chief Executive Officer of Threshold. “We look forward to the continuation of this important study with the goal of improving survival for patients with advanced STS.”

The Phase III clinical trial is being conducted by Threshold in partnership with the Sarcoma Alliance for Research through Collaboration (SARC) and under a Specialty Protocol Assessment (SPA) agreement with the US Food and Drug Administration (FDA). The study’s primary endpoint is overall survival (OS), and secondary endpoints include progression-free survival (PFS), overall response rate (ORR), pharmacokinetics and safety. The trial enrolled 640 patients at 81 study sites in Europe, Israel, North America and the Russian Federation.

Sarcomas are a group of aggressive cancers of connective tissues of the body. Currently, limited treatment options for sarcomas exist. STS is treated with surgery, chemotherapy and radiation. A combination of these modalities typically offers the best option for treating the disease successfully. The most commonly used chemotherapeutic agents used in patients with advanced STS are doxorubicin and ifosfamide; however the response rates are generally low and toxicity can be significant.

TH-302 is designed to be activated under severe tumor hypoxic conditions, a hallmark of many cancers. The drug is currently being tested in two Phase III trials, one in patients with STS and the other in patients with pancreatic cancer. TH-302 has been granted orphan drug designation by the FDA and the European Commission (EC) for treatment of STS and pancreatic cancer. Additionally, the drug is being investigated in earlier-stage trials of other solid tumors and hematological malignancies.

Source: Threshold Pharmaceuticals, Inc.

Last updated: 9/22/14; 3:15pm EST

Amgen Files for Early Approval of its Breakthrough Leukemia Drug


Today, Amgen announced that it has submitted a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) seeking approval for its leukemia drug.

Specifically, the company submitted the application for its investigational cancer immunotherapy blinatumomab for treatment of adult patients with Philadelphia-negative (Ph-) relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), a rapidly progressive cancer of the blood and bone marrow. Amgen’s blinatumomab has been granted orphan drug designation and awarded with breakthrough therapy designation from the FDA, intended to expedite review of the drug.

“We look forward to working with regulatory authorities to make blinatumomab available for adult patients with acute lymphoblastic leukemia, who experience high relapse rates and have limited treatment options,” said Sean E. Harper, MD, executive vice president of Research and Development at Amgen. “The filing for blinatumomab brings us a step closer to first realizing the potential of BiTE® technology and represents our commitment to evaluating this novel approach in a broad range of difficult-to-treat cancers.”

Blinatumomab is an investigational bispecific T cell engager (BiTE) antibody construct. BiTE® antibody constructs represent an innovative immunotherapy approach that helps the body’s immune system targeting cancer cells.

Amgen’s application includes data from a mid-stage trial of adult patients with Ph- relapsed/refractory B-precursor ALL treated with blinatumomab, which successfully met its primary endpoint, with 43 percent of patients achieving complete remission or complete remission with partial hematologic recovery within two cycles of treatment with blinatumomab. Results were presented at the American Society of Clinical Oncology (ASCO) meeting.

“Currently, there is no broadly accepted standard treatment regimen for adult patients with relapsed or refractory ALL,” said Anthony S. Stein, MD, clinical professor, Hematology/Oncology at City of Hope. “Blinatumomab has the potential to significantly advance treatment options for patients living with this difficult-to-treat disease, and the BLA submission marks an important step toward achieving this goal.”

ALL progresses rapidly and affects immature blood cells. Worldwide, the disease accounts for more than 12 percent of leukemia cases. Among the 42,000 people diagnosed with ALL worldwide, 31,000 will die from the disease. Patients with ALL have abnormal white blood cells, also known as lymphocytes, that crowd out healthy white blood cells, red blood cells and platelets, leading to infection, anemia (fatigue), easy bleeding and other serious side effects.

Source: Amgen

Last updated: 9/22/14; 11:15am EST