On December 29, 2014 Ignyta reported that the U.S. Food and Drug Administration (FDA) has granted both orphan drug designation and rare pediatric disease designation for Ignyta’s lead product candidate entrectinib for the treatment of neuroblastoma (Press release Ignyta, DEC 29, 2014, View Source [SID:1234501251]).

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"We are pleased that the FDA has provided us these designations, which highlight the potential for entrectinib to address unmet needs of patients with rare cancers," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "Although Ignyta is intrinsically motivated to continue to aggressively pursue our clinical development program for entrectinib in solid tumors for the benefit of adult and pediatric cancer patients everywhere, we are pleased that the incentives provided by these designations – including the potential for seven years of marketing exclusivity and the potential to obtain a valuable Pediatric Disease Priority Review Voucher from the FDA – can potentially provide additional avenues for creating value for our stockholders."

On December 26, 2014 Chugai Pharmaceutical reported that it obtained approval from the Japanese Ministry of Health, Labour and Welfare (MHLW) on December 26, 2014, for "unresectable melanoma with BRAF mutation," for an anti-cancer agent, BRAF inhibitor, vemurafenib tablets (brand name: Zelboraf Tablet 240mg (hereafter, "Zelboraf") (Press release Chugai, DEC 25, 2014, View Source [SID:1234501253]).
Also, Roche Diagnostics K.K. [Main Office: Minato-ku, Tokyo. President & CEO: Makoto Ogasawara (hereafter, "Roche Diagnostics")] obtained approval from the MHLW for in vitro diagnostics to detect the BRAF mutation, "cobas 4800 BRAF V600 Mutation Test," as a companion diagnostics for Zelboraf on December 2, 2014.

It is necessary to detect BRAF mutation with cobas 4800 BRAF V600 Mutation Test before use of Zelboraf for patients with unresectable melanoma with BRAF mutation. As just described, medical approach to select an appropriate therapy for each patient before administration of a drug is called personalized healthcare. It enables to avoid a treatment unlikely to show efficacy. Furthermore, since a treatment unlikely to be effective is not given, personalized healthcare increase the benefit in terms of medical economics.

It is reported that each year 1,300 to 1,400 patients (Globocan 2012) in Japan are newly diagnosed as malignant melanoma (all stages), and the number has been growing. Of these patients, 26.7 to 41.8% have the BRAF gene mutation).

Chugai and Roche Diagnostics, members of the Roche Group and pioneers in personalized healthcare, are sure that Zelboraf and cobas 4800 BRAF V600 Mutation Test can contribute to the treatment of "unresectable melanoma with BRAF mutation," a disease with poor prognosis and with high unmet medical needs. We will continue to dedicate ourselves to providing treatment options to suit individual patients.

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On December 24, 2014, Genentech reported that the U.S. Food and Drug Administration (FDA) approved a supplemental biologics license application (sBLA) for Gazyva in combination with chlorambucil chemotherapy in people with previously untreated chronic lymphocytic leukemia (CLL) (Press release Genentech, DEC 24, 2014, View Source [SID:1234501261]). The sBLA adds to the label data from Stage 2 of the CLL11 study showing significant improvements with Gazyva plus chlorambucil across multiple clinical endpoints when compared head-to-head with Rituxan (rituximab) plus chlorambucil.

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The approval includes complete response (CR) and minimal residual disease (MRD) data from Stage 2 of the study. Additionally, overall survival (OS) data was added from Stage 1 of the study comparing Gazyva plus chlorambucil to chlorambucil alone.

"Gazyva is the first and only medicine to significantly help people live without their disease worsening when combined with chlorambucil compared to Rituxan and chlorambucil in people with previously untreated chronic lymphocytic leukemia," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "These new data enhance our understanding of the disease and its treatment, and this approval affirms an important treatment option for people with this difficult-to-treat disease."

The sBLA approval updated the Gazyva prescribing information with the following data:

Gazyva plus chlorambucil helped people with previously untreated CLL live nearly a year longer without their disease worsening or death (progression-free survival; PFS) than Rituxan plus chlorambucil (median PFS: 26.7 months vs. 14.9 months, respectively. HR=0.42, 95 percent CI 0.33-0.54, p<0.0001).
Gazyva plus chlorambucil nearly tripled the number of people showing no evidence of disease (CR) compared to Rituxan plus chlorambucil (26.1 percent vs. 8.8 percent, respectively).
Of the people who achieved a complete response with or without complete recovery from abnormal blood cell counts (CR, CRi), 19 percent (18/94) of people in the Gazyva arm compared to 6 percent (2/34) of people in the Rituxan arm were MRD negative in the bone marrow, and 41 percent (39/94) of people in the Gazyva arm compared to 12 percent (4/34) people in the Rituxan arm were MRD negative in the peripheral blood. MRD negative means no residual traces of the cancer were found.
Data from the first stage of the CLL11 study showed that at nearly two years, the rate of death was 9 percent (22/238) for people who received Gazyva plus chlorambucil compared to 20 percent (24/118) for those who received chlorambucil alone (HR=0.41, 95 percent CI 0.23-0.74). The median OS has not yet been reached.

Gazyva can cause serious or life-threatening side effects including: Hepatitis B reactivation, progressive multifocal leukoencephalopathy (PML), infusion reactions, tumor lysis syndrome, infections, and low white blood cell counts. The most common side effects of Gazyva are infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea.

Gazyva, the first medicine approved with the FDA’s Breakthrough Therapy Designation, was approved for use in combination with chlorambucil in people with previously untreated CLL on November 1, 2013. Gazyva, known as Gazyvaro in Europe, was approved by the European Commission for the same indication in July 2014. Gazyva is also being investigated in a broad development program across various types of blood cancers, including multiple Phase III studies in non-Hodgkin’s lymphoma (NHL).

About the CLL11 Study

CLL11 is a Phase III, multicenter, open-label, randomized three-arm study, conducted in cooperation with the German CLL Study Group, in 781 previously untreated people with CLL and co-existing medical conditions. Stage 1 (n=589) compared Gazyva plus chlorambucil to chlorambucil alone and Rituxan plus chlorambucil to chlorambucil alone. Stage 2 (n=663) compared Gazyva plus chlorambucil directly with Rituxan plus chlorambucil. The primary endpoint of the study was PFS with secondary endpoints including overall response rate (ORR), OS, CR, median duration of response, MRD and safety profile. Results from Stage 2 and updated data from Stage 1 were presented in 2013 during the Plenary Scientific Session of the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting and published in the New England Journal of Medicine in 2014.

On December 23, 2014 Elios Therapeutics, LLC reported it received FDA approval of its Investigational New Drug (IND) application and its randomized phase IIb trial planned to enroll 120 stage III and IV (resected) melanoma patients to assess the ability of a personalized vaccine to prevent recurrence (Press release, Orbis Health Solutions, DEC 23, 2014, View Source [SID1234532480]). The trial will be conducted at a dozen leading academic cancer research hospitals in the United States.

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The Elios melanoma vaccine to be assessed in this pivotal trial will deliver personalized immunotherapy developed from the patient’s cancer cells and dendritic cells to create a specific immune response in hopes of destroying any remaining cancer cells after surgery and thereby prevent recurrence of melanoma and improve overall survival rates. Qualifying trial patients must be in stage III or IV and considered disease-free after definitive surgery and completion of standard of care therapies.

"The Elios vaccine has shown effectiveness in metastatic patients, and delivered even more promising results in the adjuvant setting. Further, the vaccine has the safety profile to allow for treatment in a preventive setting," explains George E. Peoples, MD, FACS and Chief Medical Officer, Elios Therapeutics, LLC. "Stage III and IV melanoma patients do not currently have an option for a safe, non-toxic, and effective adjuvant therapy. Melanoma at this stage recurs at an approximately 60-70 percent rate in two years, and once that happens, patients will very likely succumb to their disease. We believe that our vaccine technology can cut that rate significantly, preventing recurrence and death."

The Elios Therapeutics’ prospective, randomized, double-blind trial (NCT#02301611) is enrolling patients now, and it is anticipated that all 12-15 sites, to include the lead site at John Wayne Cancer Institute in Santa Monica, California, will open early in 2015. The trial is expected to conclude in 2018.

The vaccine being studied was developed by Elios Therapeutics’ Thomas Wagner, PhD.

"Our approach is completely different than others, in that we don’t need to identify a specific mutation or create a new drug to treat each type of cancer," explains Dr. Wagner. "This vaccine utilizes a particular patient tumor’s unique antigenic and molecular profile and a novel delivery mechanism to set the immune system to defeat that patient’s disease. Our therapy is applicable to any patient, with any tumor.

"The adjuvant therapies available for melanoma today to prevent recurrence are highly toxic and largely ineffective. We believe our vaccine has the potential to make a real impact in this setting by targeting and killing remaining metastatic cells without causing any dangerous side effects," says Dr. Wagner.