On December 1, 2014 Exelixis reported top-line results from the final analysis of COMET-2 (NCT01522443), a randomized, double-blind, controlled trial of cabozantinib in men with metastatic castration-resistant prostate cancer (mCRPC) who are suffering from moderate to severe pain despite optimized narcotic medication, and whose disease has progressed following treatment with docetaxel as well as abiraterone and/or enzalutamide (Press release Exelixis, DEC 1, 2014, View Source;p=RssLanding&cat=news&id=1993605 [SID:1234501037]). The trial did not meet its primary endpoint of alleviation of bone pain, as determined by comparing the percentage of patients in the two treatment arms who achieved a pain response at Week 6 that was confirmed at Week 12 without increase in narcotic medication. Fifteen percent of patients in the cabozantinib arm reported a pain response, compared to 17 percent of patients in the control arm receiving mitoxantrone/ prednisone. The difference in pain response between the arms was not statistically significant. The safety profile of cabozantinib in the trial was consistent with that observed in previous studies in mCRPC.

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"Following the COMET-1 top-line results announced in September, we deprioritized the cabozantinib development program in mCRPC; at that time, we also initiated a significant workforce reduction in order to focus our development efforts and financial resources on the pivotal phase 3 studies of cabozantinib in metastatic renal cell carcinoma (RCC) and advanced hepatocellular carcinoma (HCC)," said Michael Morrissey, Ph.D., president and chief executive officer of Exelixis. "With target enrollment in the METEOR study in RCC recently achieved, we anticipate top-line results in the second quarter of 2015. We also look forward to Roche and Genentech’s continued regulatory progress with cobimetinib for metastatic melanoma. The EU review is underway and the U.S. filing is expected before year-end, which could ultimately lead to our opportunity to co-promote cobimetinib in the U.S. if it is approved for this indication."

Exelixis will submit the results from the COMET program for potential presentation at a future medical meeting.

On December 1, 2014 Celator Pharmaceuticals reported that the independent Data and Safety Monitoring Board (DSMB) for the Company’s Phase 3 clinical study of CPX-351 (cytarabine:daunorubicin) Liposome for Injection versus the conventional cytarabine and daunorubicin treatment regimen (commonly referred to as 7+3) as first-line therapy in older patients with high-risk (secondary) acute myeloid leukemia (AML), has completed a planned safety review and recommended that the study continue as planned without any modifications (Press release Celator Pharmaceuticals, DEC 1, 2014, View Source [SID:1234501036]).

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"We are pleased with the DSMB recommendation to continue with the pivotal Phase 3 study of CPX-351 following this safety analysis of the first 225 randomized patients, out of a total of 309 patients who were enrolled in the study," said Arthur Louie, Chief Medical Officer of Celator Pharmaceuticals. "With the Phase 3 study having recently completed enrollment ahead of schedule, we look forward to the induction response rate analysis, which we expect in the second quarter of 2015."

The DSMB assessment was based on a pre-planned safety analysis on the first 225 randomized patients included in the study with a minimum of 60 days of follow-up. The DSMB will conduct an additional review after all patients become evaluable for safety review.

The Phase 3 study is being conducted in partnership with The Leukemia & Lymphoma Society (LLS) through its Therapy Acceleration Program (TAP), which has supported the development of CPX-351 beginning in Phase 2.

"We are excited with the progress of the Phase 3 study," said Scott Jackson, Chief Executive Officer of Celator Pharmaceuticals. "In addition to the induction response rate data, a secondary endpoint, from the study in the second quarter of next year, we expect the overall survival data, the primary endpoint, in the first quarter of 2016. We also continue to work with investigators to study CPX-351 in other AML patient populations, as well as in other hematologic malignancies, with the hope of providing improved clinical benefits to these patients."

The study (Protocol NCT01696084) enrolled patients between the ages of 60 and 75 who have pathological diagnosis of AML according to WHO criteria with confirmation of:

Therapy-related AML,
AML with a history of myelodysplasia (MDS),
AML with a history of chronic myelomonocytic leukemia (CMMoL), or
De novo AML with karyotypic abnormalities characteristic of MDS.

Patients were randomized 1:1 to receive either CPX-351 (100u/m2; days 1, 3, and 5 by 90 minute infusion) or 7+3 (cytarabine 100mg/m2/day by continuous infusion for 7 days and daunorubicin 60mg/m2 on days 1, 2, and 3). Patients are monitored for all clinical adverse events as well as laboratory evaluations. The primary efficacy endpoint of the study is overall survival. The study is being conducted in the United States and Canada, with more than 40 leading cancer centers participating.

On December 1, 2014 Pharmacyclics reported the acceptance of a Type II variation application for IMBRUVICA (ibrutinib) by the European Medicines Agency (EMA) (Press release Pharmacyclics, DEC 1, 2014, View Source [SID:1234501035]). This submission, filed by strategic partner Janssen-Cilag International NV (Janssen), represents a potential label expansion for IMBRUVICA in the European Union (EU) for the treatment of adult patients with Waldenstrom’s macroglobulinemia (WM), a rare type of B-cell lymphoma for which treatment options are limited in the EU. If approved, IMBRUVICA would be the first label specifically authorized to treat WM.

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IMBRUVICA is a first-in-class, oral, once-daily, therapy being jointly developed and commercialized in the United States (U.S.) by Pharmacyclics and Janssen Biotech, Inc. Janssen affiliates will hold the marketing authorization and market IMBRUVICA in EMEA (Europe, Middle East, Africa), as well as the rest of the world, outside the U.S.

"This additional application in the EU shows the priority and urgency with which we, and our collaboration partner Janssen, pursue the ongoing potential for IMBRUVICA," said Thorsten Graef, M.D., Ph.D., Vice President of Clinical Science, Pharmacyclics. "If approved, IMBRUVICA could address a very important unmet need for patients with WM in Europe, who currently have limited treatment options."

The acceptance of the WM Type II variation submission for IMBRUVICA triggers a $20 million milestone payment to Pharmacyclics under its collaboration agreement with Janssen Biotech, Inc.

The EMA WM filing follows the supplemental New Drug Application submission for IMBRUVICA to the U.S. Food and Drug Administration (FDA), which was submitted by Pharmacyclics in October 2014, for its use in the treatment of patients with WM. Both the FDA and EMA filings were based on data from a Phase II study evaluating the use of IMBRUVICA in WM patients, which was led by Dr. Steven Treon from the Dana-Farber Cancer Institute.

WM is a slow-growing, currently incurable, rare type of B-cell lymphoma for which there are no EU-wide approved drugs. The median age at diagnosis is 63-68 years of age and incidence rates among men and women in the EU are approximately 7.3 and 4.2 per million persons, respectively. WM begins with a malignant change to the B cell, a type of white blood cell (lymphocyte), during its maturation so that it continues to reproduce more malignant B cells.

On Decemebr 1, 2014 ImmunoCellular Therapeutics reported that the European Medicines Agency (EMA) has provided scientific advice supportive of advancing ICT-107 to a registrational phase III program in patients with newly diagnosed glioblastoma (GBM) (Press release ImmunoCellular Therapeutics, DEC 1, 2014, View Source [SID:1234501034]). The EMA guidance is consistent with the positive feedback the Company received from the US FDA relative to the scope, design and endpoints of the program and the inclusion of patients based on HLA and MGMT status. ImmunoCellular intends to finalize the design of the phase III program, ensuring harmony between US and EU trial protocols, with the goal of being in position to initiate the phase III program. The Company now is evaluating options for funding the phase III program, which may enable the initiation in 2015.

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"We appreciate the EMA’s support for conducting a phase III program with ICT-107, and for their detailed guidance on the treatment design and statistical elements of the program," said Andrew Gengos, ImmunoCellular Chief Executive Officer. "The encouragement we have received from both the US and EU regulatory authorities, and from the global neuro-oncology community, increase our confidence in ICT-107’s therapeutic potential for patients with this lethal disease. We intend to complete the design of a high quality phase III program, and to explore appropriate funding alternatives to enable next steps."

Earlier this year, ICT-107 was designated as an Advanced Therapy Medicinal Product by the EU Committee for Advanced Therapies, which should provide access in Phase III to valuable services and incentives offered by the EMA, should the Company conduct the phase III program in the EU.