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Merrimack Pharmaceuticals Receives FDA Fast Track Designation for MM-398 in Post-Gemcitabine Metastatic Pancreatic Cancer

On November 19, 2014 Merrimack Pharmaceuticals reported that the U.S. Food and Drug Administration (FDA) has granted MM-398 (nanoliposomal irinotecan injection), also known as ”nal-IRI,” Fast Track designation for the treatment of patients with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine-based therapy (Press release Merrimack, NOV 19, 2014, View Source [SID:1234500983]). Fast Track is designed by the FDA to facilitate and expedite the development and review of drugs that treat serious conditions and fill an unmet medical need.

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and is projected to be the second highest cause of death from cancer in the United States by 2020. It is a rare and deadly disease that is difficult to diagnose and has limited treatment options available.

“It is crucial to develop new therapies for patients with pancreatic cancer, particularly for those patients who have previously received gemcitabine-based therapy where there is currently no consensus on the standard of care,” said Eliel Bayever, M.D., Vice President at Merrimack and medical director for MM-398. “We will continue to work diligently on our NDA submission in an effort to bring MM-398 to patients who are facing this aggressive disease as quickly as possible.”

Merrimack is currently preparing a New Drug Application (NDA) for MM-398 in the United States for the treatment of patients with metastatic pancreatic cancer previously treated with a gemcitabine-based therapy. Fast Track designation allows sections of the NDA to be submitted to the FDA as they are completed. Based upon this designation, Merrimack expects to initiate the NDA submission in 2014 with the goal of completing the NDA submission late in the first quarter or early in the second quarter of 2015.

The US FDA and European Medicines Agency have granted MM-398 orphan drug designation in metastatic pancreatic cancer. Merrimack and Baxter International’s biopharmaceutical business (NYSE:BAX) entered into an exclusive licensing agreement to develop and commercialize MM-398 outside of the United States. Baxter expects to submit for regulatory approvals outside of the United States beginning in 2015.

3SBio Signs Exclusive Patent License Agreement for Tanibirumab, an Anti-VEGFR2/KDR mAb with PharmAbcine

On November 18, 2014 3SBio reported it has entered into an exclusive license with PharmAbcine, Inc. for the development, manufacturing and marketing of Tanibirumab, an anti-VEGFR2/KDR antibody for cancer in the territory of Greater China (including Mainland China, Taiwan, Hong Kong and Macau) and several emerging countries, including Thailand, Brazil and Russia (Press release 3SBio, NOV 18, 2014, View Source [SID:1234501350]). The deal included undisclosed upfront, milestone and royalty payments.

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Angiogenesis is correlated with disease progression and poor prognosis in many tumor types, such as colon, lung, breast and gastric cancers. VEGF and KDR (VEGFR2) are over-expressed in most malignant tumors, such as gastric, liver, NSCLC, ovarian, brain, colorectal, and breast cancers and their signaling is key regulator for tumor angiogenesis. Researchers from PharmAbcine have developed Tanibirumab, an anti-VEGFR2/KDR fully human monoclonal antibody to treat solid tumors. Tanibirumab binds KDR and blocks binding of VEGFR ligands, including VEGF-A, VEGF-C and VEGF-D. Consequently, Tanibirumab inhibits ligand-stimulated activation of KDR, therefore inhibits ligand-induced angiogenesis, proliferation, and migration of human endothelial cells.

Tanibirumab had demonstrated anti-angiogenic efficacy against several cancer types and shown cross-species cross reactivity in multiple preclinical animal models including breast cancer, glioblastoma (GBM), lung cancer, colon cancer, and hepatocellular carcinoma (HCC). In November 2011, an open-label, non-randomized, dose-escalating phase I trial began to assess the safety and pharmacokinetics of Tanibirumab, administered intravenously, in 26 patients in Korea with advanced or metastatic cancer. The trial was finished in November 2013, with good safety and efficacy results. A phase II study of Tanibirumab in GBM is being planned.

"We are pleased to collaborate with PharmAbcine and look forward to moving Tanibirumab into clinical trials in China," Dr. Jing Lou, President and CEO of 3SBio commented, "3SBio continues to seek opportunities to expand our biologics pipeline, especially novel mAb candidates for refractory or metastatic cancers and other unmet medical needs, particularly in 3SBio’s core therapeutic areas of oncology and nephrology."

"Tanibirumab is a drug candidate with great potential to treat malignant tumors," Dr. Jin-San Yoo, President and CEO of PharmAbcine commented, "3SBio is a well-established industry leader with long-term vision in the innovative biological field in China, which makes them an ideal partner for strategic collaborations. We are looking forward to working with 3SBio to maximize this opportunity and benefit tens of thousands of Chinese patients suffering for cancers and other severe diseases."

Each year, over 1 million patients are diagnosed with various types of cancer in China1.

Agios Pharmaceuticals Announces Early Phase 1 Data Showing Clinical Activity of AG-120 as a Single Agent in Advanced Acute Myeloid Leukemia (AML)

On November 18, 2014 Agios Pharmaceuticals reported the first reported safety and clinical activity for AG-120 from the ongoing Phase 1 dose escalation study in patients with IDH1-mutant positive advanced hematologic malignancies, including acute myeloid leukemia (AML) (Press release Agios Pharmaceuticals, NOV 18, 2014, View Source;p=RssLanding&cat=news&id=1990940 [SID:1234500982]). Agios has exclusive U.S. development and commercial rights to AG-120, a first-in-class, oral, selective, potent inhibitor of the mutant IDH1 enzyme. Daniel Pollyea, M.D., clinical investigator at the University of Colorado School of Medicine, will present the data in a late-breaking oral presentation today at the 26th Annual EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics being held in Barcelona, Spain. The company will webcast an investor conference call from the symposium at 10:00 a.m. EST (4:00 p.m. CET) on Wednesday, November 19, 2014.

As of October 17, 2014, the ongoing Phase 1 trial for AG-120 had enrolled 17 patients with a documented IDH1 mutation whose cancer relapsed or failed to respond (refractory) to at least one prior treatment regimen. At the time of the data cut, 14 patients with relapsed and/or refractory AML were evaluable; three patients recently initiated therapy and were not evaluable.

The initial data showed investigator assessed objective responses in seven out of 14 evaluable patients, including four complete remissions, with responses observed across the four dose levels tested, and early evidence of durability. One additional patient remains stable on study. AG-120 was well tolerated, with the majority of adverse events reported as mild to moderate. The maximum tolerated dose has not yet been reached. One patient had a dose limiting toxicity of asymptomatic grade 3 QT prolongation at the highest dose tested to date, which improved to grade 1 after AG-120 dose reduction according to treatment protocol. This patient is in complete remission and remains on AG-120. AG-120 showed favorable drug exposure and pharmacokinetics at all doses tested and also substantially reduced plasma levels of the oncometabolite 2-hydroxyglutarate (2HG), which is produced by the mutant IDH1 protein, to the level observed in healthy volunteers. The mechanism of response is consistent with differentiation, as evidenced by the maturation of the leukemic cells into infection fighting white blood cells, or neutrophils. Based on these findings, the company plans to initiate multiple expansion cohorts in the first half of 2015.

"These data show very promising evidence of clinical activity for AG-120 in AML patients with an IDH1 mutation," said Chris Bowden, M.D., chief medical officer of Agios Pharmaceuticals. "Together with the data we reported from our ongoing Phase 1 study of AG-221 in advanced hematologic cancers, our lead investigational medicine and an IDH2-mutant inhibitor, we believe IDH inhibitors could potentially change the treatment paradigm for AML patients with these mutations. We look forward to moving rapidly into multiple expansion cohorts in the first half of 2015 to further characterize the potential of AG-120."

"We are highly encouraged to see the early favorable safety profile and clinical activity of AG-120, which includes four patients who achieved complete remission," said Dr. Pollyea. "For the first time in decades, we have the potential to offer certain AML patients an improved targeted treatment for this fatal disease that has historically had limited treatment options. I am hopeful that in the future we clinicians will be able to offer well tolerated and highly effective targeted therapies for our patients who have AML harboring an IDH mutation."

Patients in the ongoing Phase 1 trial have advanced AML whose cancer was refractory to available medical treatments or relapsed after treatment. The primary objectives of the Phase 1 trial are to determine the maximum tolerated dose (MTD) and the recommended dose for further study of AG-120. Secondary objectives include characterization of the safety profile, pharmacokinetics, pharmacodynamics and early anti-tumor activity. The trial uses an open-label, dose escalating design. Patients have been enrolled to date in four cohorts of AG-120 administered at 100 mg twice a day, 300 mg once a day, 500 mg once a day and 800 mg once a day. The median age of these patients is 73 (range 42-87).

Teva Launches Liquid Formulation of TREANDA® (bendamustine HCI) Injection in U.S.

On November 18, 2014 Teva Pharmaceutical Industries reported the commercial availability of a liquid formulation of TREANDA (bendamustine HCI) Injection (Press release Teva, NOV 18, 2014, View Source;p=RssLanding&cat=news&id=1990616 [SID:1234500981]). This new liquid formulation removes the step of reconstituting lyophilized powder with sterile water prior to adding the required dose of medicine to the infusion bag and administering to a patient. By eliminating the need for reconstitution, preparation time for healthcare professionals is reduced.

"TREANDA continues to play a valuable role in the treatment of patients with CLL or indolent B-cell NHL that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen," said Paul Rittman, Vice President and General Manager, Teva Oncology. "With the new liquid formulation of TREANDA, we are not only building on the legacy of this important product, but also furthering Teva’s commitment to continuously improving our medicines."

CytRx Announces Partial Clinical Hold Affecting Aldoxorubicin Clinical Trials

On November 18, 2014 CytRx Corporation reported that the Company has received notice from the United States Food and Drug Administration (FDA) that its clinical trials for aldoxorubicin have been placed on partial clinical hold (Press release CytRx, NOV 18, 2014, View Source [SID:1234500976]). All currently enrolled patients can continue receiving aldoxorubicin treatment, or comparator drugs, as per study protocols, but no new patients can be enrolled until the clinical hold is lifted.

The FDA has indicated that the partial clinical hold is due to the reported death of a patient with advanced-stage cancer who did not qualify to participate in any of the ongoing aldoxorubicin clinical trials, but had received aldoxorubicin under the Company’s expanded access (“compassionate use”) program. At the FDA’s request, the Company will amend all aldoxorubicin study protocols to include an appropriate inclusion/exclusion criteria, an additional patient screening assessment and an evaluation of serum electrolytes prior to aldoxorubicin administration. CytRx is working diligently in collaboration with the FDA to seek the release of the clinical hold and resume enrollment in its clinical studies as expeditiously as possible.

CytRx currently believes that the partial hold issue will be expeditiously resolved and that enrollment rates and timelines for its ongoing trials will remain materially unchanged. The Company currently expects to announce preliminary results from the ongoing Phase 2 clinical trial of aldoxorubicin in Kaposi’s Sarcoma in the second quarter of 2015 and preliminary results from the ongoing Phase 2 clinical trial of aldoxorubicin in glioblastoma multiforme in the first half of 2015. CytRx remains committed to completing enrollment of its ongoing pivotal global Phase 3 trial in second-line soft tissue sarcoma by the end of 2015.