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Amgen Receives FDA Breakthrough Therapy Designation For Investigational BiTE® Antibody Blinatumomab In Acute Lymphoblastic Leukemia

On July 1, 2014 Amgen reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to investigational bispecific T cell engager (BiTE) antibody blinatumomab, for adults with Philadelphia-negative (Ph-) relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), a rapidly progressing cancer of the blood and bone marrow1 (Press release Amgen, JUL 1, 2014, View Source [SID:1234500608]).

The Breakthrough Therapy Designation was based on the results of a Phase 2 trial of 189 adult patients with Ph- relapsed/refractory B-precursor ALL treated with blinatumomab. Data from the Phase 2 trial were most recently presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the 19th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper).

“There is a high unmet need for new medicines to treat relapsed and refractory ALL patients, who have very few treatment options,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “The results from the Phase 2 trial evaluating blinatumomab in adult patients with relapsed or refractory ALL are encouraging and provide a strong basis for a regulatory filing later this year and potential approval in this serious disease.”

The FDA states that Breakthrough Therapy Designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for Breakthrough Therapy Designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy. A Breakthrough Therapy Designation conveys all of the fast-track program features, more intensive FDA guidance on an efficient drug development program, an organizational commitment involving senior managers, and eligibility for rolling review and priority review2.

In the U.S. alone, it is estimated that over 6,000 cases of ALL were diagnosed in 2013, and in the European Union, more than 7,000 cases of ALL are diagnosed each year3,4. In adult patients with relapsed or refractory ALL, median overall survival is just three to five months5.

RedHill Biopharma Acquires Phase II Oncology Drug MESUPRON from WILEX AG

On June 30, 2014 RedHill Biopharma Ltd. (NASDAQ: RDHL; TASE: RDHL) ("RedHill"), an Israeli biopharmaceutical company focused on late clinical-stage drugs for inflammatory and gastrointestinal diseases, including cancer, and WILEX AG (ISIN DE0006614720 / WL6 / FSE) ("WILEX"), a biopharmaceutical company focused on oncology, based in Munich, Germany, reported that they have signed an exclusive license agreement for the oncology drug candidate MESUPRON (Press release, RedHill Biopharma, JUN 30, 2014, View Source;LNGID=1&TMID=178&FID=1342&PID=0&IID=1857 [SID1234517321]). The MESUPRON small molecule (INN: Upamostat) is a proprietary, first-in-class, urokinase-type plasminogen activator (uPA) inhibitor administered by oral capsule. Wilex has completed several clinical studies with MESUPRON in different indications, including two Phase II proof of concept studies for pancreatic cancer and metastatic breast cancer.

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Under the terms of the agreement, RedHill acquired the exclusive development and commercialization rights to MESUPRON, excluding China, Hong Kong, Taiwan and Macao, for all indications. RedHill will pay Wilex an upfront payment of USD 1 million and potential tiered royalties on net revenues, ranging from mid-teens up to 30%. RedHill will be responsible for all development, regulatory and commercialization of MESUPRON.

MESUPRON inhibits the uPA system, which has been shown to play a key role in tumor cell growth, invasion and the metastasis process. High uPA levels are associated with poor prognosis in various solid tumor cancers, such as pancreatic, gastric, breast and prostate cancers. MESUPRON presents a promising new non-cytotoxic approach to cancer therapy with several potential mechanisms of action to inhibit both tumor metastasis and growth. MESUPRON has completed several Phase I studies and two Phase II proof of concept studies. The first Phase II study in locally advanced non-metastatic pancreatic cancer and the second study in metastatic breast cancer, established the drug’s safety and tolerability profile. The Phase II studies with MESUPRON in both indications suggested activity as measured by both tumor response rate and overall survival of patients when administered in combination with first-line chemotherapeutic agents.

Dror Ben-Asher, RedHill’s CEO, said: "The acquisition of MESUPRON reflects our commitment to patients suffering from gastrointestinal and inflammatory diseases, including related cancers such as pancreatic cancer, gastric cancer and colorectal cancer. It adds to RedHill’s pipeline of six late clinical-stage drug candidates and fits well with our risk-mitigating business model. MESUPRON is a unique non-cytotoxic approach targeting oncology indications where there is a very strong demand for better therapeutic options. Thanks to the development work conducted by Wilex, MESUPRON is supported by extensive pre-clinical and clinical data, and we believe in its potential to become an important treatment option for cancer patients. Our experienced development team is enthusiastic to advance this important new drug. We look forward to collaborating with our new partner Wilex and would like to thank them for entrusting us with the development and commercialization of MESUPRON."

About MESUPRON :

MESUPRON is a proprietary, first-in-class urokinase-type plasminogen activator (uPA) inhibitor administered by oral capsule. The uPA system has been shown to play a key role in tumor cell growth, invasion and the metastasis process. High uPA levels are associated with poor prognosis in various solid tumor cancers, such as pancreatic, gastric, breast and prostate cancers. MESUPRON presents a promising new non-cytotoxic approach to cancer therapy with several potential mechanisms of action to inhibit both tumor metastasis and growth. MESUPRON has completed several Phase I studies and two Phase II proof of concept studies. The first Phase II study in locally advanced non-metastatic pancreatic cancer and the second study in metastatic breast cancer, established its safety and tolerability profile. The Phase II studies with MESUPRON in both indications suggested activity as measured by both tumor response rate and overall survival of patients when administered in combination with first-line chemotherapeutic agents.

Boston Strategics Corporation Announces Licensing Deal with Eisai Co., Ltd.

On June 30, 2014 Boston Strategics reported that it has entered into an exclusive licensing and development agreement with Japanese global pharmaceutical company Eisai Co., Ltd., for Eisai’s oncology drug, E6201 (Press release Boston Strategics, JUN 30, 2014, View Source [SID:1234501032]).

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E6201 is a dual-targeted FLT3 and MEK inhibitor which has completed a Phase1 clinical trial showing preliminary antitumor activity and an acceptable safety profile. Building on a strong scientific rationale supported by recent preclinical data, BSC will undertake a clinical Proof of Concept (PoC) trial in the high unmet need FLT3 mutated AML patients.

Under this agreement with Eisai, BSC has worldwide rights to develop and commercialize E6201 for all Oncology indications.

This collaboration is a prime example of BSC applying its "True" Open Innovation platform to develop drug candidates with potential to significantly improve patients’ health care. As such it represents the next step toward BSC’s vision to create a novel and comprehensive approach to global pharmaceutical development.

"This is a critical milestone for BSC to validate our concept to move drug development programs forward by increasing the Probability of Success (PoS) and sharing risks with key strategic partners," says Eita Kitayama, President of Boston Strategics. "Eisai recognized the value of this approach and entrusted BSC with the development of E6201 for cancer indications to build on the foundation of this new platform. At BSC, we are deeply committed to proving that our innovative approaches can deliver breakthrough therapies with industry benchmark-beating timelines, quality, and financial investments, thus limiting the ever increasing costs of pharmaceutical innovation and development."

Tolero’s PIM Kinase Inhibitor Demonstrates Promising Activity in Preclinical Models of Urothelial Carcinoma

On June 30, 2014 Tolero Pharmaceuticals reported that recent studies in collaboration with the University of Utah examined the function of PIM kinases in cancer progression and the potential of these kinases to serve as therapeutic targets for treatment (Press release Tolero Pharmaceuticals, JUN 30, 2014, View Source [SID:1234500707]). PIM kinases are upregulated in multiple cancer indications, including lymphoma, leukemia, multiple myeloma, and prostate, gastric, and head and neck cancers. The overexpression of PIM family members often correlates with poor prognosis in tumors.

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This work demonstrates that PIM kinases are overexpressed in urothelial carcinomas taken directly from patients and that targeting the PIM kinases with a novel small-molecule inhibitor (TP-3654) reduces the growth of solid tumor xenografts where the tumorigenicity is mediated by overexpression of PIM-1 or PIM-2, as well as human bladder carcinoma tumors. TP-3654 is poised to enter IND-enabling studies and Phase I clinical testing in solid tumors and hematological malignancies.

"These data support the long-standing effort to target cell survival kinases and may provide patients with new approaches to combat difficult to treat cancers, such as bladder carcinoma. Tolero is advancing TP-3654 to further validate the PIM kinases as therapeutic targets in the clinical setting," said Steven L. Warner, PhD, Vice President of Discovery and Development at Tolero Pharmaceuticals.

Tolero is also evaluating the utility of TP-3654 in skin inflammatory conditions, such as psoriasis.

Merck’s Investigational Anti-PD-1 Antibody, Pembrolizumab, Under Regulatory Review in Europe for the Treatment of Advanced Melanoma

On June 30, 2014 Merck & Co reported that the European Medicines Agency (EMA) has accepted for review a Marketing Authorization Application (MAA) for pembrolizumab (MK-3475), the company’s investigational anti-PD-1 antibody, for the treatment of advanced melanoma. If approved by the European Commission (EC), pembrolizumab has the potential to be the first anti-PD-1 therapy in Europe (Press release Merck & Co, JUN 30, 2014, View Source [SID:1234500606]). Additional regulatory filings in other countries outside of Europe are planned by the end of 2014.

“With the five-year survival rate for patients with advanced melanoma at less than 20 percent, there remains a need to offer patients additional options,” said Dr. Roy Baynes, senior vice president, clinical development, Merck Research Laboratories. “We are pleased to have regulatory applications under review in the United States and Europe as we work toward bringing pembrolizumab to patients around the world.”

Pembrolizumab (MK-3475) is an investigational, selective, humanized, monoclonal anti-PD-1 antibody designed to reactivate anti-tumor immunity. Pembrolizumab exerts dual ligand blockade of the PD-1 pathway by inhibiting the interaction of PD-1 on T cells with its ligands PD-L1 and PD-L2.

Today, pembrolizumab is being evaluated across more than 30 types of cancers, as monotherapy and in combination. It is anticipated that by the end of 2014, the pembrolizumab development program will grow to more than 24 clinical trials, enrolling an estimated 6,000 patients at nearly 300 clinical trial sites worldwide.

The Biologics License Application (BLA) for pembrolizumab is under priority review with the U.S. Food and Drug Administration (FDA) for the treatment of patients with advanced melanoma previously-treated with ipilimumab; the PDUFA date is October 28, 2014. Pembrolizumab has been granted FDA’s Breakthrough Therapy designation for advanced melanoma. If approved by the FDA, pembrolizumab has the potential to be the first anti-PD-1 therapy approved within the United States.