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Human Anti-human PD-1 Monoclonal Antibody "OPDIVO® Intravenous Infusion 20 mg/100 mg" Receives Manufacturing and Marketing Approval in Japan for the Treatment of Unresectable Melanoma

On July 4, 2014 Ono Pharmaceutical reported that it had received manufacturing and marketing approval for the human anti-human PD-1 monoclonal antibody "OPDIVO Intravenous Infusion 20 mg/100 mg"("OPDIVO") for the treatment of unresectable melanoma (Press release Ono, JUL 4, 2014, View Source [SID:1234500642]).

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Melanoma is considered to be a form of tumor characterized by the malignant transformation of pigment-producing cells located in the skin. In Japan, there has been an unmet need for an effective treatment for patients with surgically unresectable melanoma, who have an extremely poor prognosis that no treatment exists to significantly improve.

OPDIVO is a human anti-human PD-1 monoclonal antibody. PD-1 (programmed death-1), a receptor expressed on the surface of lymphocytes, plays a role in a regulatory pathway that suppresses activated lymphocytes in the body (negative signal). Available evidence suggests that cancer cells exploit this pathway to escape from immune responses. OPDIVO is thought to provide benefit by blocking PD-1-mediated negative regulation of lymphocytes (i.e., the interaction of PD-1 with its ligands PD-L1 and PD-L2), thereby enhancing the ability of the immune system to recognize cancer cells as foreign and eliminate them. OPDIVO is the world’s first approved drug targeting PD-1.

"We are delighted to obtain a manufacturing and marketing approval as a drug targeting PD-1, which receives a lot of attention in tumor immunity, for the first time in the world." said Gyo Sagara, the President and Representative Director of ONO. "ONO would like to obtain approvals for additional indications on ongoing development for other cancers to bring many patients OPDIVO as soon as possible."

Accumulating further clinical data is important in ensuring that OPDIVO will be used more safely and effectively. ONO is committed to taking actions necessary for the proper use of OPDIVO by implementing a post-marketing use-results survey (all-case surveillance) and collecting clinical data on the safety and efficacy of OPDIVO pursuant to the conditions for its approval.

Because of the very limited number of patients treated with OPDIVO in Japanese clinical trials, ONO is required to perform a post-marketing use-results survey covering all cases until data on a certain minimum number of patients have been accumulated. Through these activities, ONO should identify the characteristics of patients to be treated with OPDIVO and collect safety and efficacy data as soon as possible, thereby taking actions necessary to ensure the proper use of OPDIVO

Japan becomes first country to approve Roche's alectinib for people with a specific form of advanced lung cancer

On July 4, 2014 Roche reported that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved alectinib for the treatment of people living with non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase fusion gene-positive (ALK+) (Press release Hoffmann-La Roche, JUL 4, 2014, View Source [SID:1234500613]). The approval was based on results from a Japanese Phase I/II clinical study (AF-001JP) for people whose tumors were advanced, recurrent or could not be removed completely through surgery (unresectable).

“The approval of alectinib, a treatment specifically targeted to ALK+ lung cancer, in Japan is great news for people living with this difficult to treat disease,” said Sandra Horning MD, Roche’s Chief Medical Officer and Head of Global Product Development. “Another interesting aspect of alectinib is that based on early studies it may also work in people living with tumors that have spread to the brain, a difficult area to reach with current medicines. Our research will continue in this area.”

Alectinib is expected to be made available in Japan later this year. Alectinib was also granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) in June 2013 for patients with ALK+ NSCLC who progressed on crizotinib. BTD is designed to expedite the development and review of medicines intended to treat serious diseases and to help ensure patients have access to them through FDA approval as soon as possible.

Global pivotal studies are currently ongoing which will further inform on the clinical value of alectinib in this disease setting as well as in treatment-naïve patients. The results of these studies will be used in future regulatory submissions in the US and in Europe.

About the Japanese Phase I/II study (AF-001JP)
This trial was conducted in 13 medical institutions in ALK fusion gene positive recurrent or advanced non-small cell lung cancer patients with a treatment history of one or more chemotherapy regimens.

The trial consisted of two phases: Phase I that evaluated safety, tolerability, pharmacokinetic parameters and recommended dose (24 patients), and a Phase II part that evaluated the efficacy and safety of the recommended dose (46 patients). The primary endpoint was response rate.

Japanese Phase I/II study (AF-001JP) results
The Phase I part of the study determined a recommended dose of 300 mg twice daily. No dose limiting toxicity was observed.

The Phase II portion of the study was conducted using the recommended dose, and demonstrated a response rate of 93.5% (43/46 patients; 95%CI: 82.1-98.6%).
– 14 patients entered the study with Central Nervous System (CNS) metastases1
– 9 of the 14 patients remained in the study without CNS or systemic progression for more than 12 months1
Progression Free Survival (PFS) at 12 months was measured as 83% (95% CI: 68-92%)1
There were no treatment-related deaths and/or grade 4 or higher serious adverse reactions assessed according to CTCAE (Common Terminology Criteria for Adverse Events) defined by the Japan Clinical Oncology Group. The most frequently observed grade 3 or higher adverse reaction was neutropenia, and the incidence of the adverse event was 4 out of 58 patients (6.9%) who were treated with 300 mg twice daily, the approved dose

FDA approves Beleodaq to treat rare, aggressive form of non-Hodgkin lymphoma

On July 3, 2014 The U.S. Food and Drug Administration today approved Beleodaq (belinostat) for the treatment of patients with peripheral T-cell lymphoma (PTCL), a rare and fast-growing type of non-Hodgkin lymphoma (NHL) (External Source US FDA , Spectrum Pharmaceuticals, JUL 3, 2014, View Source [SID:1234500610]). The action was taken under the agency’s accelerated approval program.

PTCL comprises a diverse group of rare diseases in which lymph nodes become cancerous. In 2014, the National Cancer Institute estimates that 70,800 Americans will be diagnosed with NHL and 18,990 will die. PTCL represents about 10 to 15 percent of NHLs in North America.

Beleodaq works by stopping enzymes that contribute to T-cells, a type of immune cell, becoming cancerous. It is intended for patients whose disease returned after treatment (relapsed) or did not respond to previous treatment (refractory).

"This is the third drug that has been approved since 2009 for the treatment of peripheral T-cell lymphoma," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. "Today’s approval expands the number of treatment options available to patients with serious and life-threatening diseases."

The FDA granted accelerated approval to Folotyn (pralatrexate) in 2009 for use in patients with relapsed or refractory PTCL and Istodax (romidepsin) in 2011 for the treatment of PTCL in patients who received at least one prior therapy.

The safety and effectiveness of Beleodaq was evaluated in a clinical study involving 129 participants with relapsed or refractory PTCL. All participants were treated with Beleodaq until their disease progressed or side effects became unacceptable. Results showed 25.8 percent of participants had their cancer disappear (complete response) or shrink (partial response) after treatment.

The most common side effects seen in Beleodaq-treated participants were nausea, fatigue, fever (pyrexia), low red blood cells (anemia), and vomiting.

The FDA’s accelerated approval program allows for approval of a drug based on surrogate or intermediate endpoints reasonably likely to predict clinical benefit for patients with serious conditions with unmet medical needs. Drugs receiving accelerated approval are subject to confirmatory trials verifying clinical benefit. Beleodaq also received orphan product designation by the FDA because it is intended to treat a rare disease or condition.

Beleodaq and Folotyn are marketed by Spectrum Pharmaceuticals, Inc., based in Henderson, Nevada. Istodax is marketed by Celgene Corporation based in Summit, New Jersey.

FDA approval of Beleodaq (belinostat) for Injection

On July 3, 2014 Topotarget reported that the U.S. Food and Drug Administration (FDA) has granted its partner, Spectrum Pharmaceuticals, Inc., Accelerated Approval of Beleodaq for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (R/R PTCL) (Press release TopoTarget, JUL 3, 2014, View Source [SID:1234500612]). This follows a Priority Review of the Beleodaq New Drug Application (NDA) and was an Early Approval action prior to the August 9 PDUFA (Prescription Drug User Fee Act) date.

Beleodaq was granted marketing authorization under the FDA’s accelerated approval program, which allows conditional approval of a medicine for a life-threatening disease based on early evidence suggesting clinical benefit. The approval is based on results from the BELIEF study, which enrolled 129 PTCL patients refractory to or who had failed at least one prior systemic therapy.

“With the FDA’s Accelerated Approval of Beleodaq, we have succeeded in developing a new treatment option for patients with PTCL. We are very pleased with the validation of our compound and find that it truly underlines the rationale behind Topotarget’s merger with BioAlliance Pharma in providing an even stronger orphan oncology pipeline for the combined entity, Onxeo”, says Anders Vadsholt, CEO of Topotarget.

GSK and Genmab Receive EU Authorization for Arzerra™ (ofatumumab) as First-Line Treatment for Chronic Lymphocytic Leukemia (CLL) in Combination with Chlorambucil or Bendamustine for Patients Ineligible for Fludarabine-based Therapy

On July 3, 2014 GlaxoSmithKline and Genmab reported that the European Commission (EC) has granted marketing authorization for a new indication for the use of Arzerra (ofatumumab), a human monoclonal antibody against CD20, in combination with chlorambucil or bendamustine for the treatment of patients with chronic lymphocytic leukemia (CLL) who have not received prior therapy and who are not eligible for fludarabine-based therapy (Press release Genmab, JUL 3, 2014, View Source [SID:1234500611]).

"Today’s decision by the European Commission for the first-line use of Arzerra offers a new treatment option for appropriate CLL patients and enables physicians flexibility in their choice of adjunct chemotherapy – chlorambucil or bendamustine," said Dr. Paolo Paoletti, President of Oncology, GSK.

"We are very pleased to receive this decision that Arzerra is approved in the EU in the front-line setting in combination with two different alkylating chemotherapies. This is another important milestone and we look forward to a successful launch under this new indication of the drug in Europe in the coming months. We hope to receive additional approvals in frontline across the globe in the future," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The EC authorization of the first-line indication for Arzerra (ofatumumab) is based on results from two trials:

A randomized, Phase III open-label, parallel-arm, multicenter, pivotal study (OMB110911, COMPLEMENT 1) evaluating the combination of ofatumumab and chlorambucil (N=221) versus chlorambucil alone (N=226) in CLL patients for whom fludarabine-based treatment is considered inappropriate. In this study, treatment with ofatumumab and chlorambucil demonstrated a statistically significant, 71 per cent improvement in median progression-free survival (PFS) compared to chlorambucil alone (22.4 months versus 13.1 months, respectively) (HR=0.57 [95 per cent CI, 0.45, 0.72] p<0.001).
A single-arm, multicenter, Phase II study (OMB115991) evaluating ofatumumab in combination with bendamustine in 44 patients with previously untreated CLL for whom fludarabine-based treatment was considered inappropriate. Results of this study demonstrated that ofatumumab in combination with bendamustine provided an overall response rate (ORR) of 95 per cent [95 per cent CI, 85, 99] and a complete response rate (CR) of 43 per cent.