On September 9, 2015 Takeda Pharmaceutical Company Limited (TSE: 4502) reported that the U.S. Food and Drug Administration (FDA) has granted Priority Review status to the New Drug Application (NDA) for ixazomib, the first investigational oral proteasome inhibitor for the treatment of patients with relapsed and/or refractory multiple myeloma (Press release, Takeda, SEP 9, 2015, View Source [SID:1234507434]).

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"We are encouraged that both the U.S. and European regulatory bodies have determined that the ixazomib applications qualify for an expedited review, underscoring the importance of new treatment options for patients with relapsed/refractory multiple myeloma," said Melody Brown, Vice President of Regulatory Affairs, Takeda. "Our ixazomib program is designed to evaluate whether sustained therapy with an oral proteasome inhibitor improves the outcomes of patients living with multiple myeloma. There is a significant unmet medical need in multiple myeloma and we look forward to working with the regulatory bodies to bring ixazomib to patients."

The FDA may grant Priority Review status, which includes expedited review, to the evaluation of applications for drugs that treat a serious condition and, if approved, would provide a significant improvement in safety or efficacy over existing treatment. Ixazomib was recently granted accelerated assessment by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA).

The NDA submission for ixazomib was primarily based on the results of the first pre-specified interim analysis of the pivotal Phase 3 trial, TOURMALINE-MM1. This study is an international, randomized, double-blind, placebo controlled clinical trial of 722 patients designed to evaluate the superiority of ixazomib plus lenalidomide and dexamethasone over placebo plus lenalidomide and dexamethasone in adult patients with relapsed and/or refractory multiple myeloma. Patients continue to be treated to progression in this trial and will be evaluated for long-term outcomes.

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 plasma cells, or myeloma cells, becomes cancerous and multiplies, increasing the number of plasma cells to a higher than normal level. Because plasma cells circulate widely in the body, they 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, with approximately 20,000 new cases in the U.S. and 114,000 new cases globally per year.

About Ixazomib
Ixazomib is an investigational oral proteasome inhibitor which is being studied in multiple myeloma, systemic light-chain (AL) amyloidosis, and other malignancies. 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 AL amyloidosis in 2014. It is also the first oral proteasome inhibitor to enter Phase 3 clinical trials.

Ixazomib’s clinical development program further reinforces Takeda’s ongoing commitment to developing innovative therapies for people living with multiple myeloma worldwide and the healthcare professionals who treat them. Five global Phase 3 trials are ongoing:

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

For additional information on the ongoing Phase 3 studies please visit www.clinicaltrials.gov.

On September 9, 2015 Genmab A/S (OMX: GEN) reported that Janssen-Cilag International NV (Janssen) has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for daratumumab (Press release, Genmab, SEP 9, 2015, View Source [SID:1234507428]). The submission is for daratumumab as a treatment for patients with multiple myeloma who have received at least three different lines of therapy including both a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and an IMiD.

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The submission triggers a milestone payment of USD 10 million to Genmab from Janssen. The milestone was included in Genmab’s financial guidance for 2015. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

This submission in Europe follows the completion of the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) in July this year. Both regulatory submissions include data from the Phase II study (Sirius MMY2002) of daratumumab in multiple myeloma patients who have received at least three prior lines of therapy including both a PI and an IMiD, or who are double refractory to a PI and an IMiD. However, safety and efficacy data from the Phase I/II study (GEN501) and safety data from three other studies have also been included in the submission.

"The submission of the European regulatory application for daratumumab is another significant milestone in the development of daratumumab. We have seen very promising clinical data and believe daratumumab could provide an important new treatment alternative for multiple myeloma patients if approved," said Jan van de Winkel, Ph.D, Chief Executive Officer of Genmab.

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,850 new patients will be diagnosed with multiple myeloma and approximately 11,240 people will die from the disease in the U.S. in 2015.3 Globally, it is estimated that 124,225 people will be diagnosed and 87,084 will die from the disease in 2015.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5 Patients who relapse after treatment with standard therapies, including PIs or IMiDs, have poor prognoses and few treatment options.6

About daratumumab
Daratumumab is an investigational human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It induces rapid tumor cell death through multiple immune-mediated mechanisms7, including complement-dependent cytotoxicity7, antibody-dependent cellular phagocytosis8 and antibody-dependent cellular cytotoxicity7, as well as via induction of apoptosis9 . Five Phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma and non-Hodgkin lymphoma. Daratumumab has been granted Breakthrough Therapy Designation from the US FDA.

On September 9, 2015 Celsion Corporation (NASDAQ: CLSN), a fully-integrated oncology company focused on the development of a portfolio of innovative cancer treatments, including directed chemotherapies, immunotherapies and RNA- or DNA-based therapies for the treatment of cancer and other difficult-to-treat diseases, reported that the Company has completed the integration of its June 2014 acquisition of EGEN, Inc. and has provided an update on its clinical development plans for GEN-1, the Company’s DNA-based immunotherapy for the localized treatment of ovarian and brain cancer (Press release, Celsion, SEP 9, 2015, View Source [SID:1234507427]).

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Following the acquisition of EGEN, Celsion has consolidated all early stage and preclinical assets at its Huntsville, AL facility. All clinical development, commercialization (including its Early Access Programs for ThermoDox), business development and administrative functions are now located in Lawrenceville, NJ. From this reorganization, Celsion expects to realize a 15 to 20 percent reduction in personnel and related annual operational costs.

Additionally, the Company has evaluated opportunities to maximize efficiency in its GEN-1 IL-12-based immunotherapy and has structured its clinical development program to capitalize on previously established proof-of-concept clinical data. GEN-1 has demonstrated promising clinical activity and tolerability in platinum-resistant and recurrent ovarian cancer patients, as well as synergistic anti-cancer effects in combination with bevacizumab (Avastin) in preclinical models.

The Company’s OVATION Study, a Phase 1b dose escalating trial combining GEN-1 with neo-adjuvant therapies in newly diagnosed ovarian cancer patients, is expected to commence enrollment in the second half of 2015. The first OVATION site at the University of Alabama at Birmingham has been initiated, with three additional sites expected to follow shortly. Data from this open label study is expected in the fourth quarter of 2015, and will continue into the first half of next year at higher doses of GEN-1. This trial will provide a starting dose for a follow-on Phase I/II study combining GEN-1 with Avastin and Doxil.

The Company also expects to commence a second ovarian cancer development program with initiation of a Phase I/II dose escalating trial evaluating GEN-1 in combination with Avastin and Doxil in platinum-resistant ovarian cancer patients later this year. This new combination study in platinum-resistant ovarian cancer is supported by two preclinical studies demonstrating that the combination of GEN-1 with Avastin may result in significant clinical benefit with a favorable safety profile, as well as a prior Phase 1b trial of GEN-1 plus Doxil in platinum resistant breast cancer patients.

The Company is now completing a comprehensive series of pre-clinical safety and efficacy studies, and plans to initiate a third Phase I trial combining GEN-1 with current standard of care to treat newly resected glioblastoma multiforme (GBM) brain cancer patients in 2016.

"Over the past 12 months, since our acquisition of EGEN, Inc., we have carefully evaluated our current organizational structure and collective management competencies to determine the most efficient path forward for our broad, diversified product pipeline. Our new organization will be both lean and focused on generating clinical data from our GEN-1 platform," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "As an IL-12 immunotherapy, GEN-1 has broad potential in multiple tumor types, and our clinical strategy is designed to accelerate its development, establish its clinical utility in various indications and drive it toward the market."

About GEN-1 Immunotherapy

GEN-1, designed using Celsion’s proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation. The Company has previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy in patients with peritoneally metastasized ovarian cancer, and recently completed a Phase Ib trial of GEN-1 in combination with PEGylated doxorubicin in patients with platinum-resistant ovarian cancer. GEN-1 has also demonstrated preclinical activity in glioblastoma multiforme (brain cancer) and the Company plans to initiate a Phase I study in this indication in the second half of 2015.

About Celsion Corporation

On September 9, 2015 TG Therapeutics, Inc. (NASDAQ:TGTX) reported the initiation of a Phase 1/2 clinical study that will investigate the use of TGR-1202, the Company’s oral PI3K delta inhibitor and TG-1101 (ublituximab), the Company’s glycoengineered anti-CD20 monoclonal antibody in combination with pembrolizumab the anti-PD-1 immune checkpoint inhibitor, in patients with relapsed or refractory CLL (Press release, TG Therapeutics, SEP 9, 2015, View Source [SID:1234507426]). This will be the first clinical trial evaluating the safety, tolerability and effectiveness of the triple combination of a PI3K delta inhibitor with an anti-CD20 mAb and an anti-PD-1 checkpoint inhibitor.

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"We are very excited about the launch of this combination study and its potential in treating patients with CLL. To date, engaging T-cells to fight CLL has been promising but has yet to produce the dramatic effects seen in other settings. We believe our proprietary TG-1101 plus TGR-1202 regimen in combination with T-cell enhancing therapies, like anti-PD-1, could significantly improve the outcomes for patients with CLL," stated Michael S. Weiss, the Company’s Executive Chairman and Interim Chief Executive Officer. Mr. Weiss continued, "Additionally, with our own anti-PD-L1 antibody expected to enter clinical trials next year, this trial will give us a nice head start in designing our proprietary combination clinical program."

Dr. Anthony Mato, an assistant professor in the Perelman School of Medicine at the University of Pennsylvania, Director of the Center for CLL at Penn’s Abramson Cancer Center and Study Chair of the Phase 1/2 study added, "We look forward to collaborating with TG Therapeutics on this novel combination clinical trial. Our center has been intimately involved with T-cell therapies for hematologic diseases and we are firm believers in the promise they hold broadly for cancer patients. The combination of TG-1101 and TGR-1202 has demonstrated unique tolerability and activity which we believe represents a strong backbone on which to add additional novel therapies. We believe the novel approach utilized in this study, where we will induce a response with TG-1101 and TGR-1202, followed by consolidation with anti-PD-1 therapy, could maximize the potential benefit of T-cell therapy in CLL. We are thrilled to have moved this study from concept to first patient enrolled in just a few months, and look forward to offering patients with advanced CLL new options with this novel triple combination."

The Phase 1 part of the study will evaluate the safety, tolerability, and appropriate dose of pembrolizumab when combined with TGR-1202 and TG-1101 in patients with advanced CLL. The Phase 2 part of the study will further evaluate the safety and effectiveness of the triple combination at the recommended Phase 2 dose.

This study is currently open to enrollment at the Abramson Cancer Center of the University of Pennsylvania in Philadelphia, PA. More information on this clinical study can be found at www.clinicaltrials.gov.