On June 4, 2020 Genmab A/S (Nasdaq: GMAB) reported that the European Commission (EC) has granted marketing authorization for the subcutaneous (SC) formulation of DARZALEX (daratumumab), for the treatment of adult patients with multiple myeloma in all currently approved daratumumab intravenous (IV) formulation indications in frontline and relapsed / refractory settings (Press release, Genmab, JUN 4, 2020, View Source [SID1234560821]). The approval follows a Positive Opinion by the CHMP of the European Medicines Agency (EMA) in April 2020. The SC formulation is administered as a fixed-dose over approximately three to five minutes, significantly less time than IV daratumumab, which is given over several hours. Patients currently on daratumumab IV will have the choice to switch to the SC formulation. In August 2012, Genmab granted Janssen Biotech, Inc. (Janssen) an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

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"We are extremely pleased that patients in Europe with multiple myeloma will now, like patients in the U.S., have the opportunity for treatment with the subcutaneous formulation of daratumumab. With consistent efficacy, and greater convenience for patients and health care providers with dosing time reduced from hours to just minutes and fewer infusion-related reactions, this formulation provides significant benefits for patients," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab

The approval was based on data from two studies: the Phase III non-inferiority COLUMBA (MMY3012) study, which compared the SC formulation of daratumumab to the IV formulation in patients with relapsed or refractory multiple myeloma, and data from the Phase II PLEIADES (MMY2040) study, which is evaluating SC daratumumab in combination with certain standard multiple myeloma regimens. The topline results from the COLUMBA study were announced in February 2019 and subsequently presented in oral sessions at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and the 24th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress. Updated data of the COLUMBA and the PLEIADES studies were presented during poster sessions at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2019.

About the COLUMBA (MMY3012) study
The Phase III trial (NCT03277105) is a randomized, open-label, parallel assignment study that included 522 adults diagnosed with relapsed and refractory multiple myeloma. Patients were randomized to receive either: SC daratumumab, as 1800 mg daratumumab with rHuPH20 2000 U/mL once weekly in Cycle 1 and 2, every two weeks in Cycles 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study; or 16 mg/kg IV daratumumab once weekly in Cycle 1 and 2, every two weeks in Cycles 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The co-primary endpoints of the study are overall response rate and Maximum trough concentration of daratumumab (Ctrough; defined as the serum pre-dose concentration of daratumumab on Cycle 3 Day 1).

About the PLEIADES (MMY2040) study
The Phase II trial (NCT03412565) is a non-randomized, open-label, parallel assignment study that includes 265 adults either newly diagnosed or with relapsed or refractory multiple myeloma. Patients with newly diagnosed multiple myeloma are being treated with 1,800 mg SC daratumumab in combination with either bortezomib, lenalidomide and dexamethasone (D-VRd) or bortezomib, melphalan and prednisone (D-VMP). Patients with relapsed or refractory multiple myeloma are being treated with 1,800 mg SC daratumumab plus lenalidomide and dexamethasone (D-Rd). An additional cohort of patients with relapsed and refractory multiple myeloma treated with daratumumab plus carfilzomib and dexamethasone (D-Kd) was subsequently added to the study. The primary endpoint for the D-VMP, D-Kd and D-Rd cohorts is overall response rate. The primary endpoint for the D-VRd cohort is very good partial response or better rate.

About DARZALEX(daratumumab)
DARZALEX (daratumumab) intravenous infusion is indicated for the treatment of adult patients in the United States: in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma.

DARZALEX is indicated for the treatment of adult patients in Europe via intravenous infusion or subcutaneous administration: in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and 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 therapy2. Daratumumab is the first subcutaneous CD38-directed antibody approved in Europe for the treatment of multiple myeloma. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S.

In Japan, DARZALEX intravenous infusion is approved for the treatment of adult patients: in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for the treatment of relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United States, Europe and Japan. For more information, visit www.DARZALEX.com.

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj), a subcutaneous formulation of daratumumab, is approved in the United States for the treatment of adult patients with multiple myeloma: in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for ASCT; in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for ASCT and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy; in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy; and as monotherapy, in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.3 DARZALEX FASPRO is the first subcutaneous CD38-directed antibody approved in the U.S. for the treatment of multiple myeloma.

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. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).1,4,5,6,7

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and refractory and frontline multiple myeloma settings. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases in which CD38 is expressed, such as amyloidosis and T-cell acute lymphocytic leukemia (ALL). Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA for certain indications of multiple myeloma, including as a monotherapy for heavily pretreated multiple myeloma and in combination with certain other therapies for second-line treatment of multiple myeloma.

On June 4, 2020 Servier, an independent international pharmaceutical company, reported that it has completed the acquisition of Symphogen A/S (Press release, Symphogen, JUN 4, 2020, View Source [SID1234560820]).

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Symphogen will now function as the antibody center of excellence of Servier in several different therapeutic areas including oncology. Symphogen, now a subsidiary of Servier, will keep its operational autonomy and continue to rely on its experienced employees while maintaining its headquarters in Ballerup, Denmark.

As part of the acquisition, Christophe Thurieau, Executive Director of Servier Research Institute, has been appointed Chief Executive Officer of Symphogen and Karin Garre, former Chief Operating Officer of Symphogen, has been appointed General Manager of Symphogen. Martin Olin, former
Chief Executive Officer of Symphogen, will act as an external consultant to support this transition.

Claude Bertrand, Executive Vice-President Research & Development at Servier, said: "The completion of this acquisition enables Servier to boost its antibody capabilities in oncology and in its other therapeutic areas. This efficient antibody discovery and research platform of Symphogen will strengthen our R&D capabilities and pipeline in line with our aim of making life-saving treatments available to a greater number of patients across the world."

Christophe Thurieau, Executive Director of Servier Research Institute and Chief Executive Officer of Symphogen, added: "In line with the values of Symphogen, we also strongly believe that innovation and collaboration are key to develop treatments for the benefit of patients. We are very pleased to welcome Symphogen as part of the Servier Group and look forward to further collaborating with the team on developing breakthrough antibody therapies for patients."

Karin Garre, General Manager of Symphogen, concluded: "The completion of this transaction marks a very exciting journey for Symphogen and Servier. Anchored in a pre-existing strategic collaboration, this acquisition supports the R&D strategy of Servier within antibodies thanks to the capabilities of Symphogen. As the two organizations share key values, I believe this unification is positioned for a great outcome going forward."

On June 4, 2020 Rakuten Medical, Inc. (Rakuten Medical) and The University of Texas MD Anderson Cancer Center (MD Anderson) reported a strategic alliance collaboration agreement to advance the development of new cancer therapies based on Rakuten Medical’s proprietary Illuminox technology platform (Press release, Rakuten Medical, JUN 4, 2020, View Source [SID1234560819]).

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Under the terms of the agreement, Rakuten Medical and MD Anderson will collaborate to conduct studies based on the Illuminox technology platform and to determine study designs, combination therapies, and target patient populations for future clinical trials. The alliance is designed to expand development of the technology and bring a novel therapeutic approach to patients with cancer, with an initial focus on those with head and neck cancers. This agreement expands upon an existing sponsored research agreement between Rakuten Medical and MD Anderson.

"We are honored that MD Anderson has recognized the exciting potential of our Illuminox technology by entering into this strategic alliance agreement," said Hiroshi Mikitani, Chairman and CEO of Rakuten Medical. "We believe our collaboration will allow us to develop novel treatments for different cancer types. We are energized by MD Anderson’s shared optimism and conviction to bring treatments to patients in need."

The Illuminox technology platform is based on a cancer therapy called photoimmunotherapy, developed by Dr. Hisataka Kobayashi and colleagues from the National Cancer Institute. Illuminox is a technology combining drugs and laser device systems being evaluated for the treatment of different cancers.

"The Illuminox technology represents a new form of therapy with the potential to selectively target cancer cells while sparing surrounding normal tissues through light-activatable antibody-dye conjugates," said Jeffrey Myers, M.D., Ph.D., chair of Head and Neck Surgery at MD Anderson. "We are pleased to build upon our collaborative relationship with Rakuten Medical to work toward bringing investigational treatment options forward with the goal of providing the best options for our patients."

On June 4, 2020 Hutchison China MediTech Limited ("Chi-Med") (Nasdaq/AIM: HCM) reported that the Independent Data Monitoring Committee (IDMC) of the FRUTIGA study of fruquintinib has completed a planned interim data review (Press release, Hutchison China MediTech, JUN 4, 2020, https://www.chi-med.com/chi-med-announces-the-continuation-of-phase-iii-frutiga-study/ [SID1234560818]). Based on the preset criteria, the IDMC recommended that the trial continue.

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FRUTIGA is a Phase III trial in China of fruquintinib in combination with paclitaxel (Taxol) in the treatment of patients with advanced gastric adenocarcinoma or gastroesophageal junction ("GEJ") adenocarcinoma who have progressed after first-line standard chemotherapy.

About Fruquintinib
Fruquintinib is a highly selective and potent oral inhibitor of vascular endothelial factor receptor ("VEGFR") 1/2/3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity to minimize off-target toxicities, improve tolerability and provide more consistent target coverage. The generally good tolerability in patients to date, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may be highly suitable for combinations with other anti-cancer therapies.

About FRUTIGA in Gastric Cancer
FRUTIGA is a randomized, double-blind, Phase III trial evaluating the efficacy and safety of fruquintinib combined with paclitaxel for second-line treatment of advanced gastric or GEJ adenocarcinoma. The trial is designed to enroll patients who did not respond to first-line standard chemotherapy. Subjects will receive either fruquintinib combined with paclitaxel or placebo combined with paclitaxel. Patients will be randomized at a 1:1 ratio and stratified according to factors such as stomach vs. GEJ tumor type and performance status. The primary efficacy endpoint is overall survival. Secondary efficacy endpoints include progression-free survival (as defined by RECIST 1.1), objective response rate, disease control rate, duration of response, and quality-of-life score (EORTC QLQ-C30, version 3.0). Biomarkers related to the antitumor activity of fruquintinib will also be explored.

Additional details about this study can be found at clinicaltrials.gov, using identifier NCT03223376.

FRUTIGA was initiated following the results of an open label, multi-center Phase Ib dose finding/expansion study of fruquintinib in combination with paclitaxel (Taxol) as a second-line treatment in patients with advanced gastric cancer (clinicaltrials.gov identifier NCT02415023).

Other Fruquintinib Development
Fruquintinib was approved for marketing in China by the NMPA in September 2018 and commercially launched by Eli Lilly and Company ("Lilly") in late November 2018 under the brand name Elunate. Elunate is for the treatment of patients with metastatic colorectal cancer that have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild type). Results of the FRESCO study, a Phase III pivotal registration trial of fruquintinib in 416 patients with colorectal cancer ("CRC") in China, were published in The Journal of the American Medical Association, JAMA, in June 2018 (clinicaltrials.gov identifier: NCT02314819).

Chi-Med retains all rights to fruquintinib outside of China and is partnered with Lilly in China.

Global development of fruquintinib in CRC: We are initiating a Phase III registration study, known as the FRESCO-2 study, in the U.S., Europe and Japan in CRC. FRESCO-2 is expected to start enrolling patients in mid-2020. Based on our agreement with the U.S. Food and Drug Administration (FDA), the FRESCO and FRESCO-2 studies, if positive, could support our New Drug Application (NDA).

Immunotherapy combinations: We have entered into three collaboration agreements to evaluate the safety, tolerability and efficacy of fruquintinib in combination with programmed death-1 (PD-1) monoclonal antibodies, including with tislelizumab (BGB-A317), Tyvyt (sintilimab, IBI308) and geptanolimab (GB226, genolimzumab).

On June 4, 2020 Accent Therapeutics and AstraZeneca (LSE/STO/NYSE: AZN) reported that it will collaborate to discover, develop and commercialize transformative therapeutics targeting RNA-modifying proteins (RMPs) for the treatment of cancer (Press release, Accent Therapeutics, JUN 4, 2020, View Source [SID1234560817]). The collaboration combines Accent’s expertise as a leader in the biology, target identification and drug discovery of RMP-targeting therapies with AstraZeneca’s industry leading expertise in oncology.

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Inhibition of RMPs is a new approach for addressing RNA pathobiology by targeting proteins that control many aspects of RNA biology. This class of targets represents a vast field of potentially important targets for cancer and other diseases.

José Baselga, Executive Vice President, Oncology R&D, AstraZeneca said: "The promise of RMP inhibition is a compelling area of exploration for AstraZeneca. With this collaboration, we will seek to identify novel targets and unlock the full potential of our medicines. We believe that the Accent team’s expertise in RNA-modifying protein biology and drug discovery complements AstraZeneca’s extensive research and development portfolio."

Shakti Narayan, Chief Executive Officer, Accent Therapeutics said: "This collaboration leverages both AstraZeneca’s vast cancer expertise and resources and Accent’s rich pipeline of RMP therapeutic programs to bring new and potentially life-changing medicines to patients. This collaborative effort will enable us to rapidly advance and achieve the rich therapeutic potential of these exciting programs."

Under the terms of the collaboration agreement, Accent will be responsible for research and development activities for a nominated preclinical program through to the end of Phase I clinical trials. Following completion of Phase I, AstraZeneca will lead development and commercialization activities for the nominated program, with Accent having the option to jointly develop and commercialize with AstraZeneca in the US. AstraZeneca will also have the exclusive option to license worldwide rights to two further preclinical discovery programs, for which Accent will conduct certain preclinical activities.

Accent will receive an upfront payment of $55 million and, in the event that Accent elects to jointly develop the nominated program, is eligible to receive up to $1.1 billion in additional success-based payments across all programs in the form of option fees and milestone payments, as well as tiered royalties on net sales ranging from mid-single digit to low-double digits. In the event Accent opts into co-developing and co-commercializing the nominated program, profits and losses will be split in the US.