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Phase 3 First-Line Melanoma Study of Nivolumab, an Investigational PD-1 Checkpoint Inhibitor, Demonstrates Superior Overall Survival Compared to Dacarbazine; Study Stopped Early

On June 24, 2014 Bristol-Myers Squibb reported that a randomized blinded comparative Phase 3 study (NCT01721772) evaluating nivolumab versus dacarbazine (DTIC) in patients with previously untreated BRAF wild-type advanced melanoma was stopped early because an analysis conducted by the independent Data Monitoring Committee (DMC) showed evidence of superior overall survival in patients receiving nivolumab compared to the control arm (Press release Bristol-Myers Squibb, JUN 24, 2014, View Source [SID:1234500600]). Patients in the trial will be unblinded and allowed to cross over to nivolumab. The Company will share these data with health authorities.

“The outcome of CheckMate -066 is an important milestone in the field of immuno-oncology as it represents the first well-controlled, randomized Phase 3 trial of an investigational PD-1 checkpoint inhibitor to demonstrate an overall survival benefit,” said Michael Giordano, MD, Head of Oncology Development. “Bristol-Myers Squibb is committed to continuing to lead advances in immuno-oncology and to executing our strategy to provide patients with the best opportunity to achieve the potential for long term survival.”

CheckMate -066 investigators have been informed of the decision to stop the blinded comparative portion of the trial. Bristol-Myers Squibb will ensure that patients are informed of the opportunity to continue or start treatment with nivolumab in an open-label extension as part of the Company’s commitment to characterize long-term survival. The study, which was designed in consultation with the Committee for Medicinal Products for Human Use (CHMP), was primarily conducted in countries where DTIC is a commonly-used treatment in the first-line setting, including Canada, but not at U.S. trial sites. The Company will complete a full evaluation of the final CheckMate -066 data and work with investigators on the future presentation and publication of the results.

(Press release, PeptiMed, JUN 23, 2014, View Source;newsId=20140623005412&newsLang=en [SID:1234503455])

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Celsion Corporation Completes Acquisition of EGEN, Inc.

On June 20, 2014 Celsion reported the completion of the acquisition by Celsion of substantially all of the assets of EGEN, Inc. (EGEN), a privately-held biopharmaceutical company focused on the development of nucleic acid-based therapeutics for the treatment of cancer and other difficult to treat diseases (Press release Celsion, JUN 20, 2014, View Source [SID:1234501826]). The acquisition includes EGEN’s Phase Ib DNA-based immunotherapy product candidate EGEN-001 and its therapeutic platform technologies, TheraPlas for delivery of DNA and mRNA, TheraSilence for delivery of RNA, and RAST for Cell Enabled Expression and Secretion of RNA.

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"Completing the acquisition of EGEN marks a defining event for Celsion, as it brings together leading-edge assets and capabilities with the opportunity to not only advance medicine and patient care in cancer and other serious diseases, but create long-term value for our shareholders," said Michael H. Tardugno, Celsion’s President and Chief Executive Officer. "Now, all at once a fully integrated development company with assets and capability from feasibility to commercialization, we look forward to advancing our pipeline of chemotherapies, immunotherapies and DNA or RNA-based therapies in the lab and in ongoing or planned Phase III, II and I studies. Our strong balance sheet provides us with an impressive internal development runway, as well as allows us to develop collaborative partnerships leveraging the power of our multiple platforms."

Under the terms of the agreement, CLSN Laboratories, Inc., a wholly-owned subsidiary of Celsion (CLSN Laboratories), acquired substantially all of the assets and assumed certain specified liabilities of EGEN. At the closing, Celsion issued $8.5 million worth of common stock, representing approximately 15.8% of its outstanding shares, paid approximately $3.0 million in cash to EGEN, and holds back $2.1 million worth of common stock until August 2, 2016 for expense adjustment and certain indemnification claims of Celsion. In addition to the upfront payment, a total of $30.4 million in future milestone obligations are payable to EGEN based on the successful completion of certain clinical development and licensing milestones.

The combination of Celsion and EGEN will create a fully-integrated, oncology-focused research and development company with a multi-phase clinical pipeline, platform technologies for the discovery of novel, nucleic acid-based immunotherapies and other anti-cancer DNA/RNA therapies, and expertise from bench to bedside. The transaction brings to Celsion EGEN’s lead, Phase Ib clinical candidate, EGEN-001, an IL-12 plasmid immunotherapy encased in a nanoparticle delivery system, as well as three technology platforms, TheraPlas, TheraSilence, and RAST for Cell Enabled Expression and Secretion of RNA.

The transaction complements Celsion’s lead development candidate, ThermoDox, a proprietary heat-activated liposomal encapsulation of doxorubicin, currently in a pivotal, double-blind, placebo-controlled, global Phase III trial (the OPTIMA Study) in primary liver cancer.

CLSN Laboratories has retained all EGEN employees and will be based in Huntsville, Alabama, where Celsion also plans to consolidate all of its analytical service and laboratory functions.

Cantor Fitzgerald & Co. acted as the financial advisor to Celsion. Sidley Austin LLP and O’Melveny & Myers LLP acted as legal counsel to Celsion for this transaction.

Bayer Receives Approval for Nexavar® (sorafenib) in Japan for Treatment of Differentiated Thyroid Cancer

On June 20, 2014 Bayer HealthCare reported that the Ministry of Health, Labor and Welfare (MHLW) in Japan has approved the oral multi-kinase inhibitor Nexavar (sorafenib) for the treatment of patients with unresectable differentiated thyroid carcinoma (Press release Bayer, JUN 20, 2014, View Source [SID:1234500591]). The MHLW granted Nexavar orphan drug status for thyroid carcinoma in September 2013.

“The approval of Nexavar in Japan for the treatment of unresectable differentiated thyroid carcinoma fills a significant unmet need for patients who previously lacked therapeutic options for this type of thyroid cancer,” said Dr. Joerg Moeller, Member of the Bayer HealthCare Executive Committee and Head of Global Development. “This is the third indication for Nexavar, which is already approved in more than 100 countries worldwide for hepatocellular carcinoma and advanced renal cell carcinoma, and we are pleased that this cornerstone treatment continues to reach cancer patients across the globe.”

Nexavar was approved for the treatment of progressive, locally advanced or metastatic differentiated thyroid cancer that is refractory to radioactive iodine in the United States in November 2013 and in May 2014 in the European Union.

The approval in Japan is based on data from the Phase III DECISION (stuDy of sorafEnib in loCally advanced or metastatIc patientS with radioactive Iodine refractory thyrOid caNcer) trial. In the study, sorafenib significantly extended progression-free survival (PFS), the primary endpoint of the study, compared to placebo (HR=0.59 [95% CI, 0.46-0.76]; p<0.001), which represents a 41 percent reduction in the risk of disease progression or death for patients who received sorafenib compared to placebo-treated patients. The median PFS was 10.8 months in patients treated with sorafenib, compared to 5.8 months in patients receiving placebo. The safety and tolerability profile of sorafenib in patients in the trial was generally consistent with the known profile of sorafenib. The most common treatment-emergent adverse events in the sorafenib arm were hand-foot skin reaction, diarrhea, alopecia, weight loss, fatigue, hypertension and rash. DECISION Trial Design DECISION was an international, multicenter, placebo-controlled study. A total of 417 patients with locally advanced or metastatic, progressive, RAI-refractory, differentiated thyroid cancer (papillary, follicular, Hurthle cell and poorly differentiated) who had received no prior chemotherapy, tyrosine kinase inhibitors, monoclonal antibodies that target VEGF or VEGF receptor, or other targeted agents for thyroid cancer were randomized to receive 400 mg of oral sorafenib twice daily (207 patients) or matching placebo (210 patients). Ninety-six percent of randomized patients had metastatic disease.

Vernalis and Servier achieve Research Milestone as BCL-2 inhibitor drug candidate enters Phase I

On June 19, 2014 Vernalis and Servier reported the achievement of a milestone following the treatment of the first patient in a Servier sponsored Phase I trial with a promising new drug candidate, a selectiveBCL-2 inhibitor identified through their joint oncology drug discovery collaboration (Press release, Servier, JUN 19, 2014, View Source [SID:1234508825]).

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This BCL-2 selective inhibitor is the first drug candidate stemming from an on-going collaboration between Vernalis and Servier aimed at discovering anticancer drug candidates selective for individual BCL-2 family members.

Ian Garland, CEO of Vernalis commented: "We are delighted that this new BCL-2 inhibitor candidate has now entered Phase I trials and look forward to further success from our broad, strategic collaboration with Servier."

Jean-Pierre Abastado, Director of the Center of Therapeutic Innovation in Oncology at Servier, said: "Our experience with Vernalis shows that small molecules tailored against specific targets can have very high therapeutic potential. This success was achieved through a comprehensive chemistry and biology research program with our teams identifying and characterizing this promising BCL-2 inhibitor. This new compound further extends Servier’s portfolio beyond kinase inhibitors, HDAC inhibitors and immunotherapeutic products."

About BCL-2 target:

Proteins of the BCL-2 family are crucial regulators of apoptosis. Deregulations of this protein family play a major role in the aberrant survival of tumour cells. Within this protein family, BCL-2 belongs to the pro-survival members and is often overexpressed in tumour cells. Pro-survival BCL-2 family members have been recognized as attractive therapeutic targets in oncology for more than twenty years but drug discovery research on this class of target is particularly challenging and requires innovative chemistry supported by structural biology.