On August 8, 2016 Takeda Pharmaceutical Company Limited (TSE: 4502) reported Takeda Canada has received approval from Health Canada for NINLARO (ixazomib) capsules in combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (Press release, Takeda, AUG 8, 2016, View Source [SID:1234514344]). In Canada, it is estimated that approximately 7,500 people live with multiple myeloma. The approval was primarily based on the results of the final analysis of the pivotal Phase 3 trial, TOURMALINE-MM1, which demonstrated that NINLARO in combination with lenalidomide and dexamethasone significantly extended progression-free survival, with a manageable safety profile in patients with relapsed/refractory multiple myeloma. Due to the high unmet need in multiple myeloma, the New Drug Submission for NINLARO was granted a Priority Review by Health Canada.

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"Health Canada’s approval of NINLARO represents an important step in Takeda’s unwavering commitment to combat cancer by delivering novel therapies to patients as quickly, effectively and safely as possible," says Chatrick Paul, General Manager at Takeda Canada. "We are one of the first countries in the world to gain marketing approval to deliver NINLARO as a critical treatment option for multiple myeloma patients. We are pleased that NINLARO – our first oncology prescription medicine in Canada – has a product label that is broad and robust, meaning Canadians living with relapsed/refractory multiple myeloma will now have a new effective treatment option available to them in the comfort of their home."

"Multiple myeloma, a devastating diagnosis for patients and their families, is a complicated disease that requires effective treatment options," said Dr. Donna Reece, Professor and Director of the Program for Multiple Myeloma and Related Diseases in the Department of Medical Oncology and Haematology at Princess Margaret Hospital/University of Toronto. "The approval of NINLARO offers a much-needed new option for Canadian patients with multiple myeloma who have received at least one prior therapy. Its oral delivery may help multiple myeloma patients overcome some of the logistical burdens they may face with current therapies, which are typically administered in-clinic or in-hospital requiring significant travel and time constraints."

Marketing applications for NINLARO are currently under review by several regulatory authorities around the world.

About NINLAROTM (ixazomib) capsules
NINLAROTM (ixazomib) is an oral proteasome inhibitor which is also being studied in multiple myeloma and systemic light-chain (AL) amyloidosis. It was the first oral proteasome inhibitor to enter Phase 3 clinical trials and to receive approval. NINLARO was approved by the U.S. Food and Drug Administration (FDA) in November 2015 following a priority review. In the U.S., NINLARO is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.

Ixazomib was granted orphan drug designation in multiple myeloma in both the U.S. and Europe in 2011 and for AL amyloidosis in both the U.S. and Europe in 2012. Ixazomib received Breakthrough Therapy status by the U.S. FDA for relapsed or refractory systemic light-chain (AL) amyloidosis, a related ultra orphan disease, in 2014.

The comprehensive ixazomib clinical development program, TOURMALINE, further reinforces Takeda’s ongoing commitment to developing innovative therapies for people living with multiple myeloma worldwide and the healthcare professionals who treat them. TOURMALINE includes a total of five ongoing pivotal trials – four investigating every major multiple myeloma patient population and one in light-chain amyloidosis:

TOURMALINE-MM1, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in relapsed and/or refractory multiple myeloma
TOURMALINE-MM2, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma
TOURMALINE-MM3, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma following induction therapy and autologous stem cell transplant (ASCT)
TOURMALINE-MM4, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma who have not undergone ASCT
TOURMALINE-AL1, investigating ixazomib plus dexamethasone vs. physician choice of selected regimens in patients with relapsed or refractory AL amyloidosis
In addition to the TOURMALINE program, ixazomib is being evaluated in the various therapeutic combinations for various patient populations in investigator initiated studies globally.

About Multiple Myeloma

Multiple myeloma is a cancer of the plasma cells, which are found in the bone marrow. In multiple myeloma, a group of monoclonal plasma cells, or myeloma cells, becomes cancerous and multiplies. These malignant plasma cells have the potential to affect many bones in the body, possibly resulting in compression fractures, lytic bone lesions and related pain. Multiple myeloma can cause a number of serious health problems affecting the bones, immune system, kidneys and red blood cell count, with some of the more common symptoms including bone pain and fatigue, a symptom of anemia. Multiple myeloma is a rare form of cancer. In Canada, it is estimated that approximately 7,500 people live with multiple myeloma and there are 114,000 new cases globally per year.

NINLARO- GLOBAL INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION
Ixazomib is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy

IMPORTANT SAFETY INFORMATION

SPECIAL WARNINGS AND PRECAUTIONS

Thrombocytopenia
Thrombocytopenia has been reported with ixazomib with platelet nadirs typically occurring between Days 14-21 of each 28-day cycle and recovery to baseline by the start of the next cycle. It did not result in an increase in hemorrhagic events or platelet transfusions. Monitor platelet counts at least monthly during treatment with NINLARO and consider more frequent monitoring during the first three cycles. Manage with dose modifications and platelet transfusions as per standard medical guidelines. Adjust dosing as needed.

Gastrointestinal Toxicities
Diarrhea, constipation, nausea, and vomiting have been reported with ixazomib, occasionally requiring use of antiemetic and antidiarrheal medications, and supportive care. Diarrhea resulted in the discontinuation of one or more of the three drugs in 1% of patients in the NINLARO regimen and < 1% of patients in the placebo regimen. Adjust dosing for severe symptoms.

Pregnancy
NINLARO can cause fetal harm. Females of reproductive potential should not become pregnant while taking NINLARO due to potential hazard to the fetus. Advise females of reproductive potential to use contraception during treatment and for an additional 90 days after the final dose of NINLARO. Women using hormonal contraceptives should use an additional barrier method of contraception.

Lactation
It is not known whether NINLARO is excreted in human milk. There could be potential adverse events in nursing infants. Breast-feeding should be discontinued.

SPECIAL PATIENT POPULATIONS
Hepatic Impairment: Reduce the NINLARO starting dose to 3 mg in patients with moderate or severe hepatic impairment.

Renal Impairment: Reduce the NINLARO starting dose to 3 mg in patients with severe renal impairment or end-stage renal disease requiring dialysis. NINLARO is not dialyzable.
DRUG INTERACTIONS
Co-administration of strong CYP3A inducers with NINLARO is not recommended.

ADVERSE REACTIONS
The most frequently reported adverse reactions (≥ 20%) in the NINLARO regimen, and greater than in the placebo regimen, were diarrhea (42% vs. 36%), constipation (34% vs. 25%), thrombocytopenia (28% vs. 14%), peripheral neuropathy (28% vs. 21%), nausea (26% vs. 21%), peripheral edema (25% vs. 18%), vomiting (22% vs. 11%), and back pain (21% vs. 16%). Serious adverse reactions reported in ≥ 2% of patients included thrombocytopenia (2%) and diarrhea (2%). For each adverse reaction, one or more of the three drugs was discontinued in ≤ 1% of patients in the ixazomib regimen.

Rash occurred in 19% of patients in the ixazomib regimen compared to 11% of patients in the placebo regimen The most common type of rash reported in both regimens included maculo-papular and macular rash. Rash resulted in discontinuation of one or more of the three drugs in < 1% of patients in both regimens. Manage rash with supportive care, dose modification or discontinuation.

Peripheral neuropathy was reported with NINLARO. The most commonly reported reaction was peripheral sensory neuropathy (19% and 14% in the NINLARO and placebo regimens, respectively). Peripheral motor neuropathy was not commonly reported in either regimen (< 1%). Peripheral neuropathy resulted in discontinuation of one or more of the three drugs in 1% of patients in both regimens. Monitor patients for symptoms of peripheral neuropathy and adjust dosing as needed.
For US Prescribing Information see View Source

On August 8, 2016 Helsinn, a Swiss pharmaceutical group focused on building quality cancer care products, and MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported that they have entered into an exclusive licensing, development and commercialization agreement for Pracinostat, a Phase III-ready drug candidate for the treatment of acute myeloid leukemia (AML) and other potential indications (Press release, MEI Pharma, AUG 8, 2016, View Source [SID:1234514342]). The deal provides the complementary resources from both organizations to rapidly advance Pracinostat into Phase III clinical development and expand into additional indications, including high-risk myelodysplastic syndrome (MDS).

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Under the terms of the agreement, Helsinn will get exclusive worldwide rights, including manufacturing and commercialization rights, and will be responsible for funding the global development of Pracinostat. As compensation for such grant of rights, MEI Pharma will receive near-term payments of $20 million, comprised of a $15 million upfront payment and a $5 million payment upon dosing of the first patient in the upcoming Phase III study of Pracinostat in newly diagnosed AML patients unfit to receive induction therapy. In addition, MEI Pharma will be eligible to receive up to $444 million in potential development, regulatory and sales-based milestone payments, along with additional tiered royalty payments in selected territories.

As part of the development and commercialization agreement, Helsinn and MEI Pharma will also collaborate to explore an optimal dosing regimen of Pracinostat in combination with azacitidine for the treatment of high-risk MDS. This clinical study is expected to commence in the first half of 2017. In a related transaction, Helsinn will make a $5 million equity investment in MEI Pharma.

Riccardo Braglia, Helsinn Group Vice Chairman and CEO, said: "Helsinn is delighted to be entering into this agreement with MEI Pharma for the exclusive rights on Pracinostat, a promising late-stage novel asset. In the first instance we will target acute myeloid leukemia (AML), an area of huge unmet medical need. As part of the development, we will also target additional indications. Helsinn is committed to helping people to survive cancer and offer a better quality of living with cancer.

"This agreement broadens our focus beyond cancer supportive care products and into the development of oncology therapeutics. Helsinn Therapeutics (HTU), our US sales organization, will allow us to accelerate the development and commercialization of this product, once approved, as we will be able to leverage our clinical and regulatory expertise coupled with our existing oncology specialist sales organization."

"Helsinn is an ideal strategic partner to entrust the development of Pracinostat," said Daniel P. Gold, Ph.D., President and Chief Executive Officer of MEI Pharma. "Helsinn has a strong commercial presence in the United States and, globally, has been able to create and skillfully coordinate a solid and significant network of 70 commercial partners in 90 countries. Helsinn’s antiemetic, Aloxi, is a market leader and is often used by patients receiving azacitidine, so their commercial organization is well positioned to market Pracinostat for the treatment of AML and MDS. Helsinn shares our enthusiasm for bringing Pracinostat to patients in need, and we look forward to a successful partnership for the development of the program."

Dr. Gold added: "Including MDS along with AML in the development plans was a critical component to this deal, as it significantly increases the market opportunity for Pracinostat. With this agreement in place, we are now in a great position to move forward with the Phase III study in AML, optimize the development path in MDS, and maintain lucrative economics on future commercial success."

This transaction has been approved by the boards of both companies. Destum Partners acted as an advisor to MEI Pharma on the transaction.

MEI Pharma Conference Call and Webcast
MEI Pharma’s management team will host a conference call with simultaneous webcast today, August 8, 2016, at 9:00 a.m. Eastern time to discuss the license, development and commercialization agreement with Helsinn. To access the live call, please dial 888-357-5399 (toll-free) or 440-996-5704 (international), conference ID 62028037. The conference call will also be webcast live and can be accessed at www.meipharma.com. A replay of the webcast will be available approximately one hour after the conclusion of the call.

About Pracinostat
Pracinostat is a potential best-in-class, oral histone deacetylase (HDAC) inhibitor. The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation for Pracinostat in combination with azacitidine for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) who are ≥75 years of age or unfit for intensive chemotherapy. The Breakthrough Therapy Designation is supported by data from a Phase II study of Pracinostat plus azacitidine in elderly patients with newly diagnosed AML, not candidates for induction chemotherapy, which showed a median overall survival of 19.1 months and a complete response (CR) rate of 42% (21 of 50 patients). These data compare favorably to a Phase III study of azacitidine (AZA-AML-001), which showed a median overall survival of 10.4 months with azacitidine alone and a CR rate of 19.5% in a similar patient population. The combination of Pracinostat and azacitidine was generally well tolerated, with no unexpected toxicities. The most common grade 3 4 treatment-emergent adverse events included febrile neutropenia, thrombocytopenia, anemia and fatigue.

About AML
Acute myeloid leukemia (also known as acute myelogenous leukemia) is the most common acute leukemia affecting adults, and its incidence is expected to continue to increase as the population ages. The American Cancer Society estimates about 20,830 new cases of AML per year in the U.S., with an average age of about 67 years. Treatment options for AML remain virtually unchanged for nearly 40 years. Front line treatment consists primarily of chemotherapy, while the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology recommend hypomethylating agents azacitidine or decitabine as low intensity treatment options for AML patients over the age of 60 who are unsuitable for induction chemotherapy.

On August 8, 2016 BioLineRx Ltd. (NASDAQ: BLRX; TASE: BLRX), a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, reported the signing of a collaboration agreement with The University of Texas MD Anderson Cancer Center for the investigation of BL-8040 in combination with KEYTRUDA (pembrolizumab) in pancreatic cancer (Press release, BioLineRx, AUG 8, 2016, View Source [SID:1234514340]). The study will be conducted as an investigator-sponsored study, as part of a strategic clinical research collaboration between MSD (known as Merck in the US and Canada) and MD Anderson Cancer Center aimed at evaluating Merck’s anti-PD-1 therapy, KEYTRUDA, in combination with various treatments and novel drugs.

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The open-label, single center, single-arm Phase 2 study aims to evaluate the potential of BL-8040 with KEYTRUDA in pancreatic cancer and will focus on the mechanism of action by which both drugs might synergize. In addition to assessing clinical response, the study will include multiple assessments to evaluate the biological anti-tumor effects induced by the combination. BioLineRx will supply BL-8040 for the study, which is expected to commence later this year.

In June 2016, the Company announced the filing of the regulatory submissions required to commence a separate Phase 2a study focusing on evaluating the clinical efficacy of BL-8040 in combination with KEYTRUDA, also for the treatment of patients with pancreatic cancer. This trial, named the COMBAT study, will be conducted under a collaboration agreement between BioLineRx and MSD announced in January 2016. The study is expected to commence shortly after receipt of regulatory approval, anticipated in the third quarter of 2016.

BL-8040, BioLineRx’s lead oncology platform, is a CXCR4 antagonist that has been shown in several clinical trials to be a robust mobilizer of immune cells and to be effective at inducing direct tumor cell death. Additional findings in the field of immuno-oncology suggest that CXCR4 antagonists may be effective in inducing the infiltration of anti-tumor T cells into the tumor. Therefore, when combined with KEYTRUDA, which blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, BL-8040 has the potential to enable activated T cells to better reach tumor cells in the fight against pancreatic cancer.

"We are very excited that MSD and MD Anderson Cancer Center selected BL-8040 to be tested under their collaboration. This will be the second study planned for investigating the combination of BL-8040 and KEYTRUDA, which further validates the potential of combining the two for the treatment of metastatic pancreatic cancer patients," said Kinneret Savitsky, Ph.D., Chief Executive Officer of BioLineRx. "We believe that the combination of BL-8040 with KEYTRUDA has the potential to expand the benefit of immunotherapy to cancer types currently resistant to immuno-oncology treatments, such as pancreatic cancer, which represent a significant unmet medical need. Furthermore, we view BL-8040’s inhibition of CXCR4, which may affect the immunosuppressive tumor micro-environment, as potentially synergistic with immune checkpoint inhibitors in additional oncological indications."

About Pancreatic Cancer

Pancreatic cancers of all types are the seventh most common cause of cancer deaths. According to the American Cancer Society, in 2015, nearly 50,000 were diagnosed with pancreatic cancer and an estimated 40,000 will die from the disease. The most common type of pancreatic cancer is pancreatic adenocarcinoma, which accounts for about 85 percent of cases. These adenocarcinomas start within the part of the pancreas that makes digestive enzymes. There are usually no symptoms in the early stages of the disease and symptoms that are specific enough to suggest the onset of pancreatic cancer typically do not develop until the disease has reached an advanced stage. The five-year survival rate of pancreatic adenocarcinoma is around seven percent.

About BL-8040

BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and certain hematological indications. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing apoptosis. In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, and T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.