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Idera Provides Key Updates on Clinical Development of IMO-8400 for Treatment of Waldenstrom’s Macroglobulinemia

On December 30, 2014 Idera Pharmaceuticals reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for IMO-8400, an antagonist of the endosomal Toll-like receptors (TLRs) 7, 8 and 9, for the treatment of Waldenström’s macroglobulinemia (WM) (Press release Idera Pharmaceuticals, DEC 30, 2014, View Source [SID:1234501255]). Additionally, Idera is providing a progress update on the ongoing Phase 1/2 clinical trial being conducted in WM.

Idera is currently conducting a Phase 1/2 clinical trial of IMO-8400 in patients with WM (ClinicalTrials.gov identifier NCT02092909) who have a history of relapse or failure to respond to one or more prior therapies. In B‐cell lymphomas characterized by the MYD88 L265P oncogenic mutation, including WM, preclinical studies have shown that TLR signaling is overactivated, thereby enabling tumor cell survival and proliferation. About 90 percent of WM patients are reported to harbor the MYD88 L265P oncogenic mutation.

The objectives of the trial are to evaluate the compound’s safety, tolerability and potential clinical activity. The protocol includes three dose-escalation cohorts of IMO-8400 administered subcutaneously. The trial’s independent data review committee has completed its review of four-week safety data from the second dose cohort (1.2 mg/kg/week) and has determined that Idera may open enrollment in the third dose cohort (2.4 mg/kg/week). Final 24-week safety and clinical activity data are anticipated in the second half of 2015.

Orphan drug designation is granted by the FDA Office of Orphan Products Development to drugs intended for the treatment of a rare disease or condition that affects fewer than 200,000 people in the United States. This designation provides certain incentives, including eligibility for federal grants, research and development tax credits, waiver of PDUFA filing fees and a seven-year marketing exclusivity period, once the product is approved and as long as orphan drug designation is maintained.

The approval of an orphan drug designation request does not alter the standard regulatory requirements and processes for obtaining marketing approval of an investigational drug. Sponsors must establish safety and efficacy of a compound in the treatment of a disease through adequate and well-controlled studies.

ARIAD Announces Commercialization Agreement for Iclusig in Seven Central and Eastern European Countries

On December 30, 2014 ARIAD Pharmaceuticals and Angelini Pharma, through the Austrian subsidiary CSC Pharmaceuticals reported that ARIAD has granted Angelini exclusive rights to commercialize Iclusig (ponatinib) for the indications approved by the European Medicine Agency (EMA) in Central and Eastern Europe (Press release Ariad, DEC 30, 2014, View Source [SID:1234501254]). These countries include Bulgaria, the Czech Republic, Hungary, Poland, Romania, Slovakia and Slovenia. With this distributorship in place, Iclusig will be available to patients with resistant and intolerant Philadelphia-positive leukemias in more than 23 countries in Europe.

Under the terms of the agreement, ARIAD will remain the Marketing Authorization Holder of Iclusig, and ARIAD will manage this distributorship out of its European headquarters in Lausanne, Switzerland.

Angelini will be responsible for sales and marketing, medical affairs, regulatory and reimbursement support. Angelini will book sales of Iclusig while ARIAD will supply packaged drug to Angelini. An upfront payment to ARIAD and milestones associated with commercial launches will total approximately $7.3 million. Additionally, Angelini will provide ARIAD with a substantial share of Iclusig sales in the region.

“With this agreement, we continue to move towards having Iclusig available to patients in geographies outside of our own commercial footprint,” said Marty J. Duvall, executive vice president and chief commercial officer of ARIAD. “Angelini will be an important partner for us in this region where, according to the EMA, there are approximately 8,000 patients living with chronic myeloid leukemia (CML) who may become resistant or intolerant to other approved tyrosine kinase inhibitors. Angelini has the experience and geographic reach to market and distribute Iclusig in Central and Eastern Europe.”

ARIAD received Marketing Authorization Approval for Iclusig from the European Medicine Agency in July 2013. The commercial launches of Iclusig in these Central and Eastern European countries are expected to begin in 2015.

“By partnering with ARIAD, we will be able to provide this important cancer medicine to patients in Central and Eastern Europe who have difficult-to-treat CML or Ph+ ALL and few options available to them,” said Gianluigi Frozzi, CEO of Angelini Pharma Division. “We look forward to a successful collaboration with ARIAD and to making Iclusig available to refractory CML and Ph+ ALL patients.”

Ignyta Receives Orphan Drug Designation and Rare Pediatric Disease Designation from FDA for Entrectinib for the Treatment of Neuroblastoma

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."

Contribution to the Personalized Healthcare for Melanoma Approval for BRAF inhibitor, “Zelboraf®” and its Companion Diagnostic, “cobas® 4800 BRAF V600 Mutation Test.”

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.

FDA Approves Gazyva® (Obinutuzumab) Supplemental Biologics License Application with New Data in Previously Untreated Chronic Lymphocytic Leukemia

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.

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.