Stem Cell Clinic

Genmab Announces U.S. FDA Approval of DARZALEX (daratumumab) in Combination with Bortezomib, Thalidomide and Dexamethasone for Frontline Multiple…

Company Announcement

Copenhagen, Denmark; September 26, 2019 Genmab A/S (Nasdaq:GMAB) announced today that the U.S. Food and Drug Administration (U.S. FDA) has approved the use of DARZALEX (daratumumab) in combination with bortezomib, thalidomide and dexamethasone (VTd) as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant (ASCT). The supplemental Biologics License Application (sBLA) for this indication was submitted by Genmabs licensing partner, Janssen Biotech, Inc. (Janssen) in March 2019. The U.S. FDA subsequently granted priority review to the sBLA, with a Prescription Drug User Fee Act (PDUFA) target date of September 26, 2019. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

The approval was based on data from part one of the Phase III CASSIOPEIA study of daratumumab in combination with VTd as treatment for patients newly diagnosed with multiple myeloma who are candidates for ASCT. The study is sponsored by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen.

Todays approval is an important step forward for patients with multiple myeloma. There are now three different treatment combinations that include DARZALEX for patients newly diagnosed with multiple myeloma, whether they are eligible for ASCT or not. We are grateful for the efforts of the IMF, HOVON and Janssen that led to the strong data from the CASSIOPEIA trial, which formed the basis of this new approval, said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the CASSIOPEIA (MMY3006) studyThis Phase III study is a randomized, open-label, multicenter study, run by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen, including 1,085 newly diagnosed patients with previously untreated symptomatic multiple myeloma who are eligible for high dose chemotherapy and stem cell transplant. In the first part of the study, patients were randomized to receive induction and consolidation treatment with daratumumab combined with bortezomib, thalidomide (an immunomodulatory agent) and dexamethasone (a corticosteroid) or bortezomib, thalidomide and dexamethasone alone. The primary endpoint is the proportion of patients that achieve a stringent Complete Response (sCR). In the second part of the study (currently ongoing), patients that achieved a response will undergo a second randomization to either receive maintenance treatment of daratumumab 16 mg/kg every 8 weeks for up to 2 years versus no further treatment (observation). The primary endpoint of this part of the study is progression free survival (PFS).

About multiple myelomaMultiple 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 26,000 new patients were expected to be diagnosed with multiple myeloma and approximately 13,650 people were expected to die from the disease in the U.S. in 2018.3 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.4 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

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.6 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 in Europe 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 therapy. 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 is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma and 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. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United Stated, Europe and Japan. For more information, visit http://www.DARZALEX.com.

Story continues

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 persons 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).6,7,8,9,10

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, NKT-cell lymphoma and B-cell and T-cell 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.

About Genmab Genmab is a publicly traded, international biotechnology company specializing in the creation and development of differentiated antibody therapeutics for the treatment of cancer. Founded in 1999, the company has two approved antibodies, DARZALEX (daratumumab) for the treatment of certain multiple myeloma indications, and Arzerra (ofatumumab) for the treatment of certain chronic lymphocytic leukemia indications. Daratumumab is in clinical development for additional multiple myeloma indications, other blood cancers and amyloidosis. A subcutaneous formulation of ofatumumab is in development for relapsing multiple sclerosis. Genmab also has a broad clinical and pre-clinical product pipeline. Genmab's technology base consists of validated and proprietary next generation antibody technologies - the DuoBody platform for generation of bispecific antibodies, the HexaBody platform, which creates effector function enhanced antibodies, the HexElect platform, which combines two co-dependently acting HexaBody molecules to introduce selectivity while maximizing therapeutic potency and the DuoHexaBody platform, which enhances the potential potency of bispecific antibodies through hexamerization. The company intends to leverage these technologies to create opportunities for full or co-ownership of future products. Genmab has alliances with top tier pharmaceutical and biotechnology companies. Genmab is headquartered in Copenhagen, Denmark with core sites in Utrecht, the Netherlands and Princeton, New Jersey, U.S.

Contact: Marisol Peron, Corporate Vice President, Communications & Investor Relations T: +1 609 524 0065; E: mmp@genmab.com

For Investor Relations: Andrew Carlsen, Senior Director, Investor RelationsT: +45 3377 9558; E: acn@genmab.com

This Company Announcement contains forward looking statements. The words believe, expect, anticipate, intend and plan and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with pre-clinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmabs most recent financial reports, which are available on http://www.genmab.com and the risk factors included in Genmabs final prospectus for our U.S. public offering and listing and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at http://www.sec.gov. Genmab does not undertake any obligation to update or revise forward looking statements in this Company Announcement nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law.

Genmab A/S and/or its subsidiaries own the following trademarks: Genmab; the Y-shaped Genmab logo; Genmab in combination with the Y-shaped Genmab logo; HuMax; DuoBody; DuoBody in combination with the DuoBody logo; HexaBody; HexaBody in combination with the HexaBody logo; DuoHexaBody; HexElect; and UniBody. Arzerra is a trademark of Novartis AG or its affiliates. DARZALEX is a trademark of Janssen Pharmaceutica NV.

1 American Cancer Society. "Multiple Myeloma Overview." Available at http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma.Accessed June 2016.2 National Cancer Institute. "A Snapshot of Myeloma." Available at http://www.cancer.gov/research/progress/snapshots/myeloma. Accessed June 2016. 3 Globocan 2018. United States of America Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/840-united-states-of-america-fact-sheets.pdf.4 Globocan 2018. World Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed December 2018.5 American Cancer Society. "How is Multiple Myeloma Diagnosed?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed June 2016.6 DARZALEX Prescribing information, July 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761036s019lbl.pdf Last accessed July 20197 De Weers, M et al. Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors. The Journal of Immunology. 2011; 186: 1840-1848.8 Overdijk, MB, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015; 7: 311-21.9 Krejcik, MD et al. Daratumumab Depletes CD38+ Immune-regulatory Cells, Promotes T-cell Expansion, and Skews T-cell Repertoire in Multiple Myeloma. Blood. 2016; 128: 384-94.10 Jansen, JH et al. Daratumumab, a human CD38 antibody induces apoptosis of myeloma tumor cells via Fc receptor-mediated crosslinking.Blood. 2012; 120(21): abstract 2974.

Company Announcement no. 46CVR no. 2102 3884LEI Code 529900MTJPDPE4MHJ122

Genmab A/SKalvebod Brygge 431560 Copenhagen VDenmark

Attachment

Read more:
Genmab Announces U.S. FDA Approval of DARZALEX (daratumumab) in Combination with Bortezomib, Thalidomide and Dexamethasone for Frontline Multiple...

Troy resident ‘gets it done’ with ground-breaking treatment – Troy Daily News

For Miami Valley Today

TROY Bill Willoughby has always been an optimist. This positive approach to life would serve him well after being diagnosed with non-Hodgkins lymphoma in 2015.

I was going to a doctor and at one point he said with my condition, the best he could do was try to keep me in remission, explained Bill, a Troy resident. So, he referred me to Dr. Faber at OHC for a stem cell transplant. Being an optimist, I agreed and said, Im all in. Lets get it done.

Bill went to OHC for his chemotherapy followed by the stem cell transplant for his lymphoma. OHCs stem cell transplant experts have performed more than 2300 transplants since 1989.

Stem cell transplant is a life-saving option for many people with blood cancers, explained Edward Faber, Jr., MD, MS, an OHC medical oncologist, hematologist and transplant specialist. But for Bill, months later he relapsed and the cancer was in his lungs, liver and in his bones. Weve had excellent success with stem cell transplants. Unfortunately, there are some patients for whom it just doesnt work. Our entire team was sad to learn that Bill was one of those patients.

With the cancer now in his bones, Bill was experiencing more pain than before not good for someone who still hasnt retired from the building and rental property business. So, when Dr. Faber suggested another treatment option, Bill was again optimistic.

Bill was an ideal candidate for a relatively new treatment called chimeric antigen receptor T cell immunotherapy, or CAR-T, said Dr. Faber. This is a ground-breaking treatment that has demonstrated incredible outcomes in some patients for whom all hope was lost. OHC has been using CAR-T for almost a year now and were seeing positive results. Were hopeful this will be the case for Mr. Willoughby.

CAR-T is still relatively new for treating cancers. In fact, OHC is the only adult cancer practice in the region to offer CAR-T to adults with blood cancers. With CAR-T, doctors remove immune system cells from a patient, modify them in a lab so they will recognize and kill cancer cells, then infuse them back into the patient through an IV. The cells that are injected back into the patient stay in the body, becoming what some researchers refer to as living drugs in that they are ready to attack if that same cancer returns.

I had never heard of CAR-T when Dr. Faber told me about it, Bill said. He explained that it helps your immune system cells fight the cancer. So, I looked it up, especially because I was running out of options, and it seemed like a wonderful theory. They said Im the fourth OHC patient to get this treatment.

After completing his research and weighing his options, once again, Bills response was, Im all in. Lets get this done. Bill received his CAR-T treatment in July and today hes feeling good.

I had my last scan a few weeks ago and they said the cancer in my lungs is gone, the cancer in my liver has decreased, and I still have some spots in my bones but they too have decreased, Bill said. Ive started back to work. Ive been passionate about building and construction since I was 15 years old. Now Im 70 and Im still into it, although I mostly subcontract the work. But I have rental properties and still do that maintenance work.

CAR-T has demonstrated success like no other treatment before. It received breakthrough therapy designation from the Food and Drug Administration, which means the process for approval is moved along more quickly after initial clinical trials show strong results. The procedure is currently performed in a designated center, originally as a hospital inpatient procedure that is now being administered in a hospital outpatient department.

OHC is launching new clinical trials to determine if it can be given in a doctors office treatment suite setting, like OHC, said Dr. Faber. And soon, we hope to introduce clinical trials that will look to expand CAR-T to treat other cancers, like solid tumors.

We still have a way to go with CAR-T and other immunotherapies, but if its successful, it will forever change the way the world treats cancer. Its a whole new frontier for medicine, Dr. Faber added.

Ive always been an optimist and a Christian, and I look at this as a great thing thats happened to me, Bill added. So does my family. Ive already recommended it to a couple people I know whove also run out of options. I tell them to call Dr. Faber and see if he can get it for them. When your chances become limited and then you learn about this, you start to see a possible light at the end of the tunnel.

OHC is the only adult cancer group in the region to offer this advanced treatment to adults. For more information including an educational video, visit https://www.ohcare.com/service/car-t-cell-therapy/ or call (888) 649-4800.

Provided photo Pictured is OHC patient Bill Willoughby back at work thanks to CAR T-cell immunotherapy.

Willoughby undergoes stem cell transplant

See the article here:
Troy resident 'gets it done' with ground-breaking treatment - Troy Daily News

The unexpected functional diversity of reactive astrocytes – Baylor College of Medicine News

When the brain is injured or diseased astrocytes are the first to respond. They become reactive and play roles that can be both beneficial and deleterious, but little is known about how these diverse responses to injury are regulated.

In his lab at Baylor College of Medicine, Dr. Benjamin Deneen, professor of neurosurgery and theCenter for Stem Cell and Regenerative Medicine, has long been studying astrocytes, the most abundant cells in the brain. In this publication, he and his colleagues reported surprising discoveries regarding both the generation and activity of the first responders to brain injury.

Reactive astrocytes are associated with most forms of neurological disorders, from acute injury to degeneration, but their contributions to disease are only now coming to light, Deneen said.

In the current study, Deneen and his colleagues focused on identifying a regulator of reactive astrocytes. They looked into nuclear factor I-A (NFIA), a known regulator of astrocyte development, and investigated whether it also was involved in the generation and regulation of reactive astrocytes.

First, they determined that NFIA is abundant in human pediatric and adult reactive astrocytes found in a host of neurological injuries. Then, to explore the role NFIA plays in the response of reactive astrocytes to injury, the researchers turned to mouse models. They generated mice in which NFIA was specifically eliminated in astrocytes, and compared the reactive astrocyte response of these NFIA-deficient mice to that of mice with NFIA, after different types of neurological injury.

The results were surprising, said Deneen, who holds the Dr. Russell J. and Marian K. Blattner Chair and is a member of the Dan L Duncan Comprehensive Cancer Center at Baylor. Until now, it was thought that, regardless of the type of injury or where it occurred in the central nervous system, reactive astrocytes would respond in the same way. Knocking out NFIA allowed us to uncover a previously unknown layer of functional diversity in reactive astrocytes.

When white matter injuries occurred in the spinal cord of NFIA-deficient mice, reactive astrocytes were generated and migrated toward the injury, but were not able to remodel the injured blood brain barrier as well as the reactive astrocytes of normal mice did. Consequently, the white matter was not repaired.

But when the researchers tested the response to a different form of injury in another region of the central nervous system a stroke in the cerebral cortex they observed something different. While normal mice (with NFIA) responded to stroke by producing reactive astrocytes that migrated toward the injury to repair the bleeding, NFIA-deficient mice did not generate reactive astrocytes and the injury was not healed. In both cases, in the spinal cord and in the cerebral cortex, the injury was not properly repaired, but the underlying reasons were different in each case.

These findings suggest that NFIAs function in reactive astrocytes is dependent upon the type of injury and brain region in which the injury occurs. In the cerebral cortex, NFIA is crucial for making reactive astrocytes, while in the spinal cord NFIA is important for sealing off leaking blood vessels. These results hint at an extensive reservoir of reactive astrocyte responses that vary according to form and location of injury, Deneen said.

In addition, the researchers began to define the molecular mechanisms underpinning the generation of reactive astrocytes. They found that NFIA directly regulates the production of thrombospondin 4, an essential regulator of the generation of reactive astrocytes that had been previously identified in the lab of co-author Dr. Chay T. Kuo, associate professor of cell biology and neurobiology at Duke University.

Although our study was conducted in mice and more research is needed, we think our findings may reflect what occurs in people, as NFIA also is abundantly present in reactive astrocytes in both pediatric and adult neurological injuries, Deneen said.

We also are interested in investigating the role NFIA plays in reactive astrocytes involved in neurodegenerative diseases, such as Alzheimers and Parkinsons disease. Its possible it has a completely different set of functions in these conditions, Deneen said.

The study appears in The Journal of Clinical Investigation.

Other contributors of this work include Dylan Laug, Teng-Wei Huang, Navish A. Bosquez Huerta, Yu-Szu Huang, Debosmita Sardar, Joshua Ortiz, Jeffrey C. Carlson, Benjamin R. Arenkiel, Carrie A. Mohila, Stacey M. Glasgow and Hyun Kyoung Lee. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Texas Childrens Hospital, Duke University and the University of California San Diego.

This work was supported by grants from the National Multiple Sclerosis Society (RG-1501-02756 and FG-1607-25417), the National Institutes of Health (NIH) (NS096096 and S071153), the National Heart, Lung, and Blood Institute (NHLBI), NIH (T32-HL902332) and the David & Eula Winterman Foundation MS Research Endowment.

By Ana Mara Rodrguez, Ph.D.

See more here:
The unexpected functional diversity of reactive astrocytes - Baylor College of Medicine News

Stem Cell Assay Market Overview by Industry Chain Information, Upstream Raw Materials & Downstream Industry 2017 2025 – Herald Space

Get Sample Copy of this report at https://www.persistencemarketresearch.com/samples/13462?source=atm

The undifferentiated biological cells that can differentiate into specialized cells are called as stem cells. In the human body during early life and growth phase, stem cells have the potential to develop into other different cell types. Stem cells can differ from other types of cells in the body. There are two types of stem cells namely the embryonic stem cells and adult stem cells. Adult stem cells comprise of hematopoietic, mammary, intestinal, neural, mesenchymal stem cells, etc. All stem cells have general properties such as capability to divide and renew themselves for long period. Stem cells are unspecialized and can form specialized cell types. The quantitative or qualitative evaluation of a stem cells for various characteristics can be done by a technique called as stem cell assay. The identification and properties of stem cells can be illustrated by using Stem Cell Assay. The new developments in the field of stem cell assay research related to the claim of stem cell plasticity have caused controversies related to technical issues. In the study of stem cell assay, most conflicting results arise when cells express stem cell characteristics in one assay but not in another. The most important factor is that the true potential of stem cells can only be assessed retrospectively. The retrospective approach refers to back drop analysis which provides quantitative or qualitative evaluation of stem cells. The development in embryonic & adult stem cells assay will be beneficial to the global stem cell assay market. Stem cell assays find applications in pharmaceutical & biotechnology companies, academic & research institutes, government healthcare institutions, contract research organizations (CROs) and others. The influential factors like chronic diseases, increased investment in research related activities, and technological advancements in pharmaceutical & biotech industry is anticipated to drive the growth of the global stem cell assay market during the forecast period. The cost of stem cell based therapies could be one of the major limiting factor for the growth of the global stem cell assay market.

Ask an expert at https://www.persistencemarketresearch.com/ask-an-expert/13462?source=atm

The global stem cell assay market has been segmented on the basis of kit type, application, end user and region. The global stem cell assay market can be differentiated on the basis of kit type into human embryonic stem cell kits and adult stem cell kits. The adult stem cell kit includes hematopoietic stem cell kits, mesenchymal stem cell kits, induced pluripotent stem cell kits (IPSCs), and neuronal stem cell kits. The adult stem cell kits are projected to witness the highest CAGR during the forecast period due to the ease of use, cost & effectiveness of this type of kit in stem cell analysis.

Based on application global stem cell assay market is based on drug discovery and development, therapeutics and clinical research. The therapeutics segment includes oncology, dermatology, cardiovascular treatment, orthopedic & musculoskeletal spine treatment, central nervous system, diabetes and others.

Depending on geographic segmentation, the global stem cell assay market is segmented into five key regions: Asia Pacific, North America, Europe, Latin America, and Middle East & Africa. North America is expected to contribute significant share to the global stem cell assay market. The stem cell assay market in Europe, has gained impetus from the government & industrial initiatives for stem cell based research and the market in Europe is expected to grow at a remarkable pace during the forecast period. The major players in the global stem cell assay market include GE Healthcare, Promega Corporation, Thermo Fisher Scientific Inc., Merck KGaA, Cell Biolabs, Inc., Hemogenix Inc., Stemcell Technologies Inc., Bio-Rad Laboratories Inc., R&D Systems Inc., and Cellular Dynamics International Inc.

Request to view TOC at https://www.persistencemarketresearch.com/toc/13462?source=atm

See more here:
Stem Cell Assay Market Overview by Industry Chain Information, Upstream Raw Materials & Downstream Industry 2017 2025 - Herald Space