On August 17, 2016 Genmab A/S (Nasdaq Copenhagen: GEN) reported that its licensing partner, Janssen Biotech, Inc. has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for the use of daratumumab (DARZALEX) in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who received at least one prior therapy (Press release, Genmab, AUG 17, 2016, View Source [SID:1234514628]). Schedule your 30 min Free 1stOncology Demo! "We are thrilled that an application to expand the current label to include treatment of multiple myeloma patients who received at least one prior therapy has been submitted so soon after the initial FDA approval of daratumumab in November 2015. The data from the Phase III CASTOR and POLLUX studies on which the submission is based was unprecedented, meriting a Breakthrough Therapy Designation from the FDA. We believe that if approved, daratumumab has the potential to make a substantial positive impact in the treatment of patients with multiple myeloma who have relapsed on their previous therapy," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.
In July 2016, daratumumab was granted a Breakthrough Therapy Designation (BTD) in this patient population. The submission of the application triggers milestone payments totaling USD 15 million to Genmab from Janssen. The milestone payments were included in Genmab’s financial guidance for 2016 that was published on August 9, 2016. In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize daratumumab.
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A request for Priority Review has been submitted by Janssen with this sBLA. The FDA will inform Janssen whether a Priority Review has been granted by calendar day 60 of their review starting today. If the FDA grants Priority Review, the review should be completed within 6 months from today.
The submission includes data from two Phase III studies: the CASTOR study of daratumumab in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone alone in patients with relapsed or refractory multiple myeloma, and the POLLUX study of daratumumab in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with relapsed or refractory multiple myeloma. The submission also included data from the Phase I study of daratumumab in combination with pomalidomide and dexamethasone in relapsed or refractory multiple myeloma. These data will also be used as the basis for a potential regulatory submission to the European Medicines Agency (EMA).
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 30,330 new patients are expected to be diagnosed with multiple myeloma and approximately 12,650 people are expected to die from the disease in the U.S. in 2016.3 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would 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 proteasome inhibitors or immunomodulatory agents, have poor prognoses and few treatment options.6
About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.7 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. For more information, visit www.DARZALEX.com.
Daratumumab is a 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 is believed to induce rapid tumor cell death through programmed cell death, or apoptosis,7,8 and multiple immune-mediated mechanisms, including complement-dependent cytotoxicity,7,8 antibody-dependent cellular phagocytosis9,10 and antibody-dependent cellular cytotoxicity.7,8 In addition, daratumumab therapy results in a reduction of immune-suppressive myeloid derived suppressor cells (MDSCs) and subsets of regulatory T cells (Tregs) and B cells (Bregs), all of which express CD38. These reductions in MDSCs, Tregs and Bregs were accompanied by increases in CD4+ and CD8+ T cell numbers in both the peripheral blood and bone marrow.7,11
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline settings are currently ongoing, and 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, non-Hodgkin’s lymphoma and a solid tumor.
Year: 2016
Funding Includes Support of Clinical Development of Anti-CD47 Antibody Program in Multiple Cancer Immunotherapy Trials
On August 16, 2016 Tioma Therapeutics, Inc., a venture-stage biopharmaceutical company developing anti-CD47 antibodies for the treatment of solid and hematologic cancers, reported it has raised $86 million in Series A venture financing (Press release, Tioma Therapeutics, AUG 16, 2016, View Source [SID:1234514627]). Proceeds from this financing will be used to further develop Tioma’s antibody portfolio, including its lead drug candidate – an anti-CD47 immune checkpoint inhibitor – through advanced proof-of-concept in human clinical trials.
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The Series A financing was co-led by RiverVest Venture Partners (including 3×5 RiverVest Fund), Novo Ventures, Roche Venture Fund and S.R. One, Limited (the corporate venture capital arm of GlaxoSmithKline). Pursuant to this financing, John McKearn, PhD, of RiverVest Venture Partners, Peter Moldt, PhD, of Novo Ventures, Carole Nuechterlein of Roche Venture Fund and Jill Carroll of S.R. One will serve on the company’s board of directors, with Dr. McKearn serving as Chairman of the Board.
"We find CD47 to be an extremely interesting target in the evolving cancer immunotherapy landscape," said Peter Moldt, PhD, Partner at Novo Ventures. "We believe Tioma Therapeutics, with its portfolio of diverse, functionally heterogeneous antibodies, is well positioned to test the CD47 hypothesis in the clinic."
The company also announced today that John Donovan will lead the Tioma executive management team as President, Chief Executive Officer and member of the board of directors. John has more than two decades of industry experience, first as an investment banker and then as a member of senior leadership within several biotechnology companies. Most recently, he was a co-founder of Alios BioPharma and served as its Chief Business Officer and Chief Financial Officer through its acquisition by Johnson & Johnson.
"We are delighted to have John’s strong leadership skills, extensive corporate strategy experience and financial expertise to guide Tioma’s management team during this new phase of the company’s development," commented John McKearn, PhD, Managing Partner, RiverVest Venture Partners.
"We’re pleased by the degree of investor interest in this financing and thrilled to have enabled the robust advancement of our therapeutic antibodies well into clinical development," stated John Donovan, President and Chief Executive Officer of Tioma Therapeutics. "We’re particularly excited by the prospect of using these compounds in combination with other therapeutic agents, such as PD-L1/PD-1 inhibitors. We believe we have the ability to meaningfully improve outcomes for patients suffering from a variety of debilitating cancers."
About Immunotherapy and CD47
There are two distinct but interdependent arms of the immune system that work in concert to recognize cancer cells and destroy them. Both the innate and adaptive immune responses are capable of recognizing and destroying cancer cells but tumors evolve mechanisms to evade them.
Immunotherapy is intended to "wake" the immune system so that it can recognize and destroy cancer cells. Currently approved immuno-oncology therapies have been effective in a subset of patients despite harnessing only the adaptive immune response. Anti-CD47 antibodies have the potential to promote coordination by the innate and adaptive immune systems with both acting in concert to attack tumors.
TRILLIUM THERAPEUTICS RECEIVES FDA CLEARANCE TO PROCEED WITH TTI-621 IN CLINICAL TRIAL TARGETING SOLID TUMORS AND MYCOSIS FUNGOIDES
On August 17, 2016 Trillium Therapeutics Inc. (NASDAQ: TRIL; TSX: TR), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported that the US Food and Drug Administration (FDA) has provided the company clearance to initiate a Phase 1 clinical trial of its lead drug candidate, TTI- 621 (SIRPaFc), in solid tumors and mycosis fungoides (Press release, Trillium Therapeutics, AUG 17, 2016, View Source [SID:1234514625]). Patient enrollment is anticipated to commence by the end of the year. Trillium is developing TTI-621 as a novel checkpoint inhibitor of the innate immune system, and the drug is currently being evaluated in an ongoing Phase 1 dose escalation study in patients with relapsed or refractory hematologic malignancies. Schedule your 30 min Free 1stOncology Demo! "The FDA’s acceptance of this IND application is another important milestone for our company, as the study of TTI-621 in select tumor types could lead to a more thorough understanding of its mechanism of action, and may bring us one step closer to a much needed treatment option for patients," said Dr. Niclas Stiernholm, chief executive officer of Trillium Therapeutics. "We seek to gain insight into the tumor micro-environment before, during and after treatment with TTI- 621. This will help us learn how to best use TTI-621 CD47 blockade in combination with other anti-cancer drugs and better design the commercial development path for this agent."
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In the multicenter, open-label, Phase 1 trial, TTI-621 will be delivered by intratumoral injection in patients with relapsed and refractory, percutaneously-accessible cancers. Patients will be enrolled in sequential dose cohorts to receive intratumoral injections of TTI-621 that increase in dose and dosing frequency to characterize safety, pharmacokinetics, pharmacodynamics and preliminary evidence of antitumor activity. In addition, detailed evaluation of serial, on-treatment tumor biopsies of both injected and non-injected cancer lesions will help characterize tumor microenvironment changes anticipated with CD47 blockade.
Accurexa Announces Positive FDA Pre-IND Meeting Outcome for its ACX-31 Brain Cancer Program
On August 16, 2016 Accurexa Inc. (the "Company" or "Accurexa") (ACXA), a biotechnology company focused on the development of novel neurological therapies to be directly delivered into the brain reported that it received a written response from the FDA (U.S. Food and Drug Administration) regarding a pre-IND (Investigational New Drug) meeting request for its ACX-31 program for the local delivery of temozolomide as adjunctive therapy to BCNU, both chemotherapeutics, in the treatment of brain tumors in conjunction with surgery and radiation (Press release, Accurexa, AUG 16, 2016, View Source [SID1234516522]). The FDA confirmed the acceptability of a 505(b)(2) application pathway with one first-in-human Phase 2 clinical trial followed by one Phase 3 clinical trial.
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Key Points of Written Response:
Acceptability of a 505(b)(2) application pathway confirmed
Pharmacology studies appear adequate
Non-clinical studies appear adequate with the exception of one GLP-compliant toxicology study in a single animal species using the route and schedule of administration proposed for the planned Phase 2 trial to be required
Phase 2 clinical trial strongly recommended to be conducted in patients with relapsed/recurrent glioblastoma
Proposed Phase 2 trial primary endpoints appear adequate
If an adequately designed Phase 2 trial demonstrates tolerability and suggests activity, FDA would encourage Accurexa to request an End-of-Phase 2 meeting to discuss the design of an adequate and well-controlled, randomized Phase 3 trial
"We are very pleased with the outcome of the FDA meeting. The FDA’s acceptance of a 505(b)(2) application pathway reduces the cost and time for the development of our ACX-31 Brain Cancer program than it would otherwise require. The FDA provided valuable guidance and we continue moving our ACX-31 program forward towards clinical development," said George Yu, MD, Accurexa’s President & CEO.
Under a 505(b)(2) application pathway the Company can rely on studies of previously approved drugs that were not conducted by the Company. The benefits of a 505(b)(2) application include lower risk due previous drug approvals, lower cost and accelerated development due to fewer studies, than a typical new drug application.
Other Events
On August 16, 2016, OncoGenex Pharmaceuticals, Inc. (Company) announced results from the final analysis of AFFINITY, the Phase 3 trial of custirsen in men with metastatic castrate-resistant prostate cancer (CRPC) whose disease has progressed after treatment with docetaxel (Filing, 8-K, OncoGenex Pharmaceuticals, AUG 16, 2016, View Source [SID1234515887]). The trial did not meet the primary endpoint of demonstrating a statistically significant improvement in overall survival for patients treated with custirsen in combination with cabazitaxel/prednisone compared to cabazitaxel/prednisone alone. The median overall survival for the custirsen arm was 14.2 months versus 13.4 months for the control arm with a hazard ratio of 0.946. Safety data were consistent with those observed in previous trials of custirsen in CRPC.
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As a result of these data and previous custirsen findings, the Company plans to initiate discussions with the U.S. Food and Drug Administration (FDA) to evaluate options related to an early analysis of the Phase 3 ENSPIRIT trial investigating custirsen in combination with docetaxel as second-line chemotherapy in patients with non-small cell lung cancer. In the Company’s proposal to the FDA, the trial’s hypothesized hazard ratio of 0.75 and the p-value for the final survival analysis will remain the same, with a minimal reduction in power and a small change in the critical hazard ratio from 0.84 to 0.83. The ENSPIRIT trial is over 90% enrolled and more than 80% of the events have occurred. The Company believes this is sufficient to assess the potential effect of custirsen in non-small cell lung cancer.
The Company has also engaged MTS Health Partners, LP as its advisor to assist with the exploration of strategic alternatives.
A copy of the Company’s press release is filed as Exhibit 99.1 to this Current Report on Form 8-K.