publication date: Jan. 9, 2015

Accelerated Approval Granted To Opdivo in Metastatic Melanoma


FDA approved Opdivo (nivolumab) injection for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor.

This indication was granted under an accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. Opdivo is sponsored by Bristol-Myers Squibb Company.

The efficacy of Opdivo was evaluated based on a single-arm, non-comparative planned interim analysis of the first 120 patients who received Opdivo with a minimum of six months follow-up in the phase III CheckMate-037 trial.

Opdivo achieved a 32 percent response rate (95% CI: 23, 41) with a dosing strength and frequency of 3 mg/kg intravenously over 60 minutes every two weeks. Three percent of patients achieved a complete response, and 28 percent achieved a partial response. Of 38 patients with responses, 33 patients had ongoing responses with durability of response ranging from 2.6+ to 10+ months, which included 13 patients with ongoing responses of six months or longer. Responses to Opdivo were demonstrated in both patients with and without BRAF mutation.


FDA approved a supplemental biologics license application for Gazyva (obinutuzumab) in combination with chlorambucil chemotherapy in people with previously untreated chronic lymphocytic leukemia.

The sBLA adds to the label data from Stage 2 of the phase III 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 and minimal residual disease data from the study. Additionally, overall survival data was added from Stage 1 of the study comparing Gazyva plus chlorambucil to chlorambucil alone. Gazyva is sponsored by Genentech, a member of the Roche Group.

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 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); and that Gazyva plus chlorambucil nearly tripled the number of people showing no evidence of disease compared to Rituxan plus chlorambucil (26.1 percent vs. 8.8 percent, respectively).


FDA approved an updated version of MarginProbe, a medical device that enables real-time detection of cancer at the surface of excised tissue specimens during breast-conserving cancer surgery. MarginProbe is developed by Dune Medical Devices.

Surgeon feedback, design ideas and miniaturization engineering were the driving forces behind the development of MarginProbe 1.2, according to Dune. The new version uses the same diagnostic technology as version 1.1, improving functionality, portability and overall ease of use, including a smaller size and a brighter screen.


FDA granted Fast Track designation to SGX301 (synthetic hypericin) for the first-line treatment of cutaneous T-cell lymphoma.

The designation is designed to facilitate the development and expedite the review of new drugs. Soligenix Inc., the drug’s sponsor, will be eligible to submit a new drug application for SGX301 on a rolling basis, permitting the FDA to review sections of the NDA prior to receiving the complete submission. Additionally, NDAs for fast track development programs ordinarily will be eligible for priority review, which imparts an abbreviated review time of approximately six months. SGX301 has already received orphan drug designation from the FDA.

SGX301 is a first-in-class photodynamic therapy utilizing visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a potent photosensitizer which is topically applied to skin lesions and then activated by fluorescent light 16 to 24 hours later. In a phase II study in CTCL, patients experienced a statistically significant (p < 0.04) improvement with topical hypericin treatment whereas the placebo was ineffective: 58.3 percent compared to 8.3 percent, respectively.


Polaris Group’s lead product candidate, ADI-PEG 20 (pegylated arginine deiminase), received orphan drug designations for the treatment of malignant pleural mesothelioma in the U.S. and the European Union.

Having completed a successful randomized phase II trial in argininosuccinate synthetase -deficient MPM patients with ADI-PEG 20 as monotherapy, Polaris is currently conducting a phase 1 trial of ADI-PEG 20 in combination with pemetrexed and cisplatin, the approved first-line treatment for MPM, for the treatment of MPM and non-squamous non-small cell lung carcinoma.

Polaris is also conducting clinical trials on ADI-PEG 20 both as monotherapy and in combination with other agents, for the treatment of several other indications including breast cancer, melanomas, ovarian cancer and hepatocellular carcinoma.

ADI-PEG 20 is designed to deplete the external supply of arginine, which causes arginine-dependent cancer cells to die while leaving the patient’s normal cells unharmed.


Amgen and Kite Pharma entered into a strategic research collaboration and license agreement to develop and commercialize novel Chimeric Antigen Receptor T cell immunotherapies based on Kite’s engineered autologous cell therapy platform and Amgen’s array of cancer targets.

Kite will be responsible for conducting all preclinical research and cell manufacturing and processing through Investigational New Drug filing. Each company will then be responsible for clinical development and commercialization of their respective CAR therapeutic candidates, including all related expenses.

Kite will receive from Amgen an upfront payment of $60 million, as well as funding for R&D costs through IND filing. Kite will be eligible to receive up to $525 million in milestone payments per Amgen program based on the successful completion of regulatory and commercialization milestones, plus tiered high single- to double-digit royalties for sales and the license of Kite’s intellectual property for CAR T cell products. Amgen is eligible to receive up to $525 million in milestone payments per Kite program, plus tiered single-digit sales royalties. Further terms of the agreement were not disclosed.


Taiho Oncology Inc., a subsidiary of Taiho Pharmaceutical Co. Ltd., completed its rolling New Drug Application submission to FDA for TAS-102 (trifluridine and tipiracil hydrochloride). TAS-102 is an oral combination anticancer drug under investigation for the treatment of refractory metastatic colorectal cancer.

TAS-102 was granted Fast Track designation in September 2014, with the first sections of the rolling submission accepted by the FDA on Oct. 16, 2014. The submission is supported by the results from the phase III RECOURSE trial of TAS-102 in 800 mCRC patients, whose disease had progressed after or who were intolerant to standard therapies.

The trial met the primary efficacy endpoint of statistically significant improvement in overall survival versus placebo (HR = 0.68, p < 0.0001) and demonstrated a safety profile consistent with that observed in earlier clinical trials.

TAS-102 is an oral combination investigational anticancer drug of trifluridine and tipiracil hydrochloride. FTD is an antineoplastic nucleoside analog, which is incorporated directly into DNA, thereby interfering with the function of DNA. The blood concentration of FTD is maintained via TPI, which is an inhibitor of the FTD-degrading enzyme, thymidine phosphorylase.

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