Novel Role, EZH2 Boosts Creation Of Ovarian Cancer Blood Vessels

10 07 15'

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A protein associated with cancer progression when abundant inside of tumors also unexpectedly regulates the creation of new blood vessels that feed the tumor outside, a research team led by scientists at The University of Texas MD Anderson Cancer Center reports in the August edition of Cancer Cell.

By using a nanoparticle-based gene-silencing system to block production of the protein, the researchers inhibited formation of new blood vessels (angiogenesis) to the tumor and caused a steep reduction in tumor burden in a mouse model of ovarian cancer.

“We’ve discovered that EZH2 promotes tumor growth by shutting down genes that block formation of new blood vessels,” said study senior author Anil Sood, M.D., professor in UT MD Anderson’s departments of Gynecologic Oncology and Cancer Biology. “Tumors treated with current anti-angiogenesis drugs eventually progress. This study presents a new mechanism for angiogenesis that opens the door for development of new treatment approaches.”

EZH2 is a member of a group of proteins known to repress gene expression. It has been associated with the progression and spread of bladder, breast, prostate and gastric cancers and one type of cancer of the pharynx.

Increased EZH2 is tied to decreased survival for patients

An examination of 180 ovarian cancer tumors found that the protein was overexpressed in the tumor in 66 percent of cases and in the endothelial cells of 67 percent of samples. Endothelial cells line the inside of blood vessels and are crucial to angiogenesis.

Increased expression of the protein in either tumor or endothelial cells was associated with late-stage and high-grade disease and decreased median survival. Patients with increased EZH2 levels in their tumors had a median survival of 2.5 years compared to 7.33 years for those without. For overexpression in the endothelial cells, the difference was 2.33 years versus 8.33 years for those with normal levels.

In a series of lab experiments, the team found that vascular endothelial growth factor (VEGF), a known stimulator of angiogenesis, boosts the level of EZH2 in endothelial cells. EZH2 then silences the vasohibin1 (VASH1) gene, which normally inhibits blood-vessel-formation. Silencing the EZH2 gene in the tumor’s endothelial cells reactivates VASH1, reducing angiogenesis and ovarian cancer growth in mice.

Silencing ezh2 reduces tumor weight

The ezh2 gene was targeted separately in tumor cells and in endothelial cells by delivery of small interfering RNA (siRNA) short snippets of RNA that block gene expression to mice with one of two strains of ovarian cancer.

— Treating mice with siRNA that silenced ezh2 in the tumor-associated endothelial cells reduced average tumor weight by 62 percent and 40 percent in the two strains of cancer compared with control mice.

— Hitting the gene only in the tumor had little significant effect on tumor burden.

— Silencing in both tumor and endothelial cells reduced average tumor weight by 83 percent and 65 percent in the two cancer strains.

Additional tests showed that silencing ezh2 reduced both he number of blood vessels serving the tumors and ovarian cancer cell proliferation while increasing programmed death of tumor cells.

siRNA delivery system relies on crustacean shell component

Sood and co-author Gabriel Lopez-Berestein, M.D., professor in UT MD Anderson’s Department of Experimental Therapeutics, have developed delivery systems that package siRNA with a fatty ball called a liposome to silence specific genes in cancer cells.

“Those systems are quite effective for delivery to tumors and tumor cells but not as effective for delivery to tumor vasculature,” Sood said. They jointly developed a new delivery system that packages siRNA into chitosan nanoparticles. Chitosan is derived from a chitin, a structural component in the shells of crustaceans.

Chitosan nanoparticles carry a slight positive electrical charge, making them attractive to the mostly negatively charged endothelial cells. The nanoparticles penetrate the tumor by way of its vasculature, so the new system hits both targets.

The nanoparticles accumulate in the cancer cell and vasculature passively as they circulate in the blood stream. Chitosan nanoparticles are so small that they can flow through tiny holes in the tumor vasculature. They also accumulate in other organs, so the researchers are working to add a targeting molecule that will limit nanoparticle uptake to tumors and their vasculature.

The study was funded by grants from the National Cancer Institute, the Ovarian Cancer Research Fund, Inc., the U.S. Department of Defense, the Zarrow Foundation, the Marcus Foundation, the Betty Anne Asche Murray Distinguished Professorship, the Gynecologic Cancer Foundation/OCRF Ann Schreiber Ovarian Cancer Research grant, the Meyer and Ida Gordon Foundation, the National Institute of Child Health and Development, the GCF-Molly Cade Ovarian Cancer Research Grant and the Taiwan National Science Council.

Co-authors with Sood and Lopez-Berestein are three co-first authors: Chunhua Lu, M.D., Hee Dong Han, Ph.D., and Lingegowda Mangala, Phi.D., and Guillermo Armaiz-Pena, Ph.D., Wei Hu, M.D., Ph.D., Rebecca. Stone, M.D., Mian M.K. Shahzad, M.D., Jeong-Won Lee, M.D., Edna Mora, M.D., Amy Carroll, M.D., Koji Matsuo, Whitney Spannuth, M.D., Rosemarie Schmandt, Ph.D., Nicholas Jennings, Blake Goodman, Alpa M. Nick, M.D., Hye Sun Kim, M.D., and Robert Coleman, M.D., all of MD Anderson’s Department of Gynecological Oncology; Murali K. Ravoori and Vikas Kundra of MD Anderson’s Department of Experimental Diagnostic Imaging; Robert Langley, Ph.D., of MD Anderson’s Department of Cancer Biology; Ming-Chuan Hsu and Mien-Chie Hung of MD Anderson’s Department of Cellular and Molecular Biology; George Calin, M.D., Ph.D., and Lopez-Berestein of the Department of Experimental Therapeutics; Calin, Lopez-Berestein and Sood are members of MD Anderson’s Center for RNA and Non-Coding RNA; and Jae Yun Lim and Ju-Seog Lee, Ph.D., of MD Anderson’s Department of Systems Biology; Rouba Ali-Fehmi, M.D., Department of Pathology at Wayne State University; Christopher Newton, Ph.D., and Laurent Ozbun, Ph.D., Department of Cell and Cancer Biology at the National Cancer Institute; Adnan Munkarah, M.D., of Women’s Health Services, Henry Ford Health System in Detroit; Robert Jaffe, M.D., of the Center for Reproductive Sciences, University of California, San Francisco; Eylem Ozturk Guven, Ph.D., and Emir Denkbas, Ph.D., of Hacettepe University, Nanotechnology and Nanomedicine Division, Ankara, Turkey; Ya-Huey Chen, Ph.D., of the Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University and Hospital, Taiwan; Long-Yuan Li, Ph.D., Department of Biotechnology, Asia University, Taiwan; and Michael Birrer, M.D., Ph.D., Department of Medicine, Harvard Medical School, Massachusetts General Hospital Cancer Center.

Source: University of Texas M. D. Anderson Cancer Center

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Chip-Based And Mobile Blood Diagnosis

10 06 15'

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The analysis takes just a few minutes and the doctor knows straight-away whether there are any pathogens in the blood. An improved marker-free technique provides the basis for faster analysis, whether in a hospital or for mobile blood donations.

If a person loses a large amount of blood the consequences can be critical. That’s why adequate quantities of donated blood have to be kept available in hospitals and blood banks. In Egypt doctors collect blood by traveling to towns and villages and conducting blood donation sessions in a laboratory bus. The problem is that 25 per cent of the samples taken contain pathogens, including HIV, hepatitis and syphilis. As these diseases can be passed on in transfusions, the contaminated blood cannot be used. Conventional fast tests are not suitable in most cases for mobile use.

In future a rapid and robust analysis technique could help. A few drops of blood could be tested in the bus to check whether it can be used. Only if the result is positive will the doctors take a larger quantity from the donor. The basis for this has been provided by research scientists at the Fraunhofer Institute for Biomedical Engineering IBMT in Sankt Ingbert under an EU project also involving the Egyptian company VACSERA, Mivitec GmbH, the Institute for Analytical Sciences ISAS in Dortmund and the University of Lausitz. “Our consortium has developed a glass chip which has antibodies on it. Tiny surface oscillations are induced in the chip. If the relevant virus binds with an antibody, the oscillation changes,” explains Dr. Thomas Velten, Head of Department at the IBMT. The technique is not new, but the chip that has been developed offers advantages. Usually there is only one measurement field and a reference field next to it, positioned a just a few millimeters apart. But the temperature there can be different. On the new chip, the measurement and reference fields are divided into narrow strips which in each case are located right next to each other. As a result the chip is more resistant to fluctuations in temperature. What’s more, the new chip consists of four analysis squares, which means that the blood can be examined for four different pathogens during each test.

It has also been difficult up till now for laboratory workers to avoid contact with the blood and protect themselves from infections while conducting tests in the bus. The researchers at the IBMT have therefore encapsulated the chip. This makes the blood follow a defined course on the chip, protecting the user. A first prototype of the measurement device is being presented at the Medica trade fair from November 18 to 21 in Düsseldorf (Hall 10, Stand 10F05). Dr. Velten estimates that the device could come onto the market in about three years’ time.

Source:
Dr. Thomas Velten

Fraunhofer-Gesellschaft

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Ciphergen Announces Publication Of Data Describing Application For Evaluating Patients With Blood Disorder

10 05 15'

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Ciphergen
Biosystems, Inc. (Nasdaq: CIPH) today announced that its clinical
development partner Ohio State University published an article describing
the use of Surface Enhanced Laser Desorption/Ionization Time of Flight
(SELDI-TOF) mass spectrometry for the diagnosis and clinical evaluation of
thrombotic thrombocytopenic purpura (TTP), a hematologic disease. The
article appears in the current issue of Spectroscopy.

“A diagnostic test that can rapidly determine enzyme activity is needed
to help clinicians make the correct diagnosis, initiate timely therapy and
predict the risk of the disease recurrences for patients with thrombotic
thrombocytopenic purpura, a devastating hematological disorder,” said
Haifeng M. Wu, M.D., Assistant Professor of Pathology and Medicine and
Director of Clinical Coagulation Laboratory at Ohio State University
Medical Center, author of the paper and Ciphergen collaborator. “This study
successfully illustrates the unique application of SELDI-TOF mass
spectrometry for measuring enzyme activity and evaluating auto-antibody
activity — both of which are key parameters in the pathology and
progression of TTP.”

In November 2006, Ciphergen and OSU announced a collaborative agreement
to develop and clinically validate a diagnostic test to detect TTP. Under
the terms of the agreement, and Ciphergen will optimize the assay to
measure enzyme and antibody inhibition activity, and will jointly conduct
multi-center studies to validate the test. Ciphergen Biosystems and Ohio
State University intend to validate the assay’s clinical utility using
SELDI-TOF technology across a larger patient population.

About Thrombotic Thrombocytopenic Purpura (TTP)

TTP is a blood disorder characterized by low platelets, low red blood
cell count (caused by premature breakdown of the cells), neurological
abnormalities and sometimes abnormalities in kidney function. In most
cases, this disease is caused by a deficiency in or auto-antibodies to an
enzyme called ADAMTS13, which cleaves von Willebrand Factor. Loss of this
enzyme causes platelet clumping and red blood cell destruction that are the
hallmarks of TTP.

About Ciphergen

Ciphergen Biosystems, Inc. is dedicated to the discovery, development
and commercialization of novel high-value diagnostic tests that help
physicians diagnose, treat and improve outcomes for patients. Ciphergen,
along with its prestigious scientific collaborators, has ongoing diagnostic
programs in oncology/hematology, cardiology and women’s health with an
initial focus in ovarian cancer. Based in Fremont, California, more
information about Ciphergen can be found on the Web at
ciphergen.

Safe Harbor Statement

This press release contains
forward-looking statements. For purposes of the Private Securities
Litigation Reform Act of 1995 (the “Act”), Ciphergen disclaims any intent
or obligation to update these forward-looking statements, and claims the
protection of the Safe Harbor for forward-looking statements contained in
the Act. Examples of such forward-looking statements include statements
regarding the utility of using SELDI-TOF mass spectrometry for measuring
enzyme activity and evaluating auto-antibody activity and Ciphergen’s
efforts to optimize an assay for such measurements to be used in a
diagnostics test. Actual results may differ materially from those projected
in such forward-looking statements due to various factors, including the
possibility that Ciphergen’s efforts may not proceed as anticipated.
Investors should consult Ciphergen’s filings with the Securities and
Exchange Commission, including its Form 10-Q filed November 20, 2006, for
further information regarding these and other risks related to the
Company’s business.

Ciphergen Biosystems, Inc.
ciphergen

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Despite Promising Laboratory Data Bone Cancer Treatment Ineffective

10 04 15'

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Ewing sarcoma is the second most common type of primary bone cancer seen in children and young adults. Patients with relapsed or refractory Ewing sarcoma have a poor outcome with conventional therapies. Cytarabine decreases the levels of a certain key protein in Ewing sarcoma cells and has demonstrated preclinical activity against Ewing sarcoma cell lines in the laboratory. Treatment of Ewing sarcoma that relapses is difficult. A new study published in Pediatric Blood & Cancer evaluated a phase II clinical trial of a potential new treatment approach for relapsed Ewing sarcoma using cytarabine.

Ten patients were treated. While one patient’s tumor stayed stable in size for approximately 4 months while receiving the drug, none of the ten patients had smaller tumors after treatment with cytarabine. This result is disappointing since laboratory studies indicated that cytarabine might be an effective drug for these patients. In addition, these patients with Ewing sarcoma developed lower blood counts than expected from these doses of cytarabine. The fact that the drug was not found to be effective is yet another example in which laboratory data do not always translate into success in treating patients.

“Cytarabine is not an effective agent for patients with Ewing sarcoma and this drug should be used with caution in heavily pretreated patients with solid tumors due to the significant impact of the drug on blood counts,” says Steven DuBois, co-author of the study. This study demonstrates the difficulties of extending promising therapeutic targets observed in the laboratory to effective treatments in patients. It also emphasizes the need for more predictive preclinical models.

To view the abstract for this article, please click here.

Pediatric Blood & Cancer publishes the highest quality manuscripts describing basic and clinical investigations of blood disorders and malignant diseases of childhood, including diagnosis, treatment, epidemiology, etiology, biology and molecular and clinical genetics of these diseases as they affect children, adolescents and young adults. The journal also includes studies on such treatment options as hematopoietic stem cell transplantation, immunology and gene therapy. For more information, please visit here.

Wiley-Blackwell was formed in February 2007 as a result of the acquisition of Blackwell Publishing Ltd. by John Wiley & Sons, Inc., and its merger with Wiley’s Scientific, Technical, and Medical business. Together, the companies have created a global publishing business with deep strength in every major academic and professional field. Wiley-Blackwell publishes approximately 1,400 scholarly peer-reviewed journals and an extensive collection of books with global appeal. For more information on Wiley-Blackwell, please visit interscience.wiley.

Wiley-Blackwell

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Cooper Researchers Uncover Important Link In Sepsis Survival

10 03 15'

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Cooper University Hospital’s internationally renowned team of Critical Care and Emergency Department physicians have completed original research that could have major implications on the future development of effective treatments for patients with severe sepsis and septic shock, the leading cause of death in intensive care units. The study, which was funded in part by the Emergency Medicine Foundation and the American Heart Association, will be published in the January 2007 edition of Annals of Emergency Medicine

Sepsis is the body’s inflammatory response to severe infection.

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Molecules With Interesting Anti-Clotting Properties Identified By Researchers

10 02 15'

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Virginia Commonwealth University researchers have discovered a new mechanism to inhibit key enzymes that play a major role in clotting disorders, which could lead to novel therapies to treat clots in the lungs and those localized deep in the body in areas such as the legs.

Antithrombotic disorders occur when the effect of thrombin, a protein involved in coagulation, is inhibited, rendering blood unable to clot effectively. These disorders are considered common and can be fatal. Additionally, clotting disorders arise due to complications from other diseases like cancer. Although there are a number of anticoagulation drugs available — heparins and warfarins — some patients develop adverse reactions to the therapy and must be closely monitored.

In a study published in the Journal of Biological Chemistry, Umesh R. Desai, Ph.D., a professor in the Department of Medicinal Chemistry at the VCU School of Pharmacy, lead investigator on the study, reported on the design of three highly complex molecules with unique anticoagulant properties that were prepared in the laboratory. According Desai, these molecules, known as sulfated DHPs, are completely different from anticoagulants used in the clinic today including heparins, coumarins and hirudins.

The team demonstrated that the molecules were able to inhibit the ability of critical enzymes involved with the cascade of events involved in blood clotting. Specifically, the molecules prevent the normal action of thrombin and factor Xa, which are the critical enzymes targeted by current anticoagulant therapy.

“We have identified a new mechanism that may prevent clotting. This approach may result in new drugs for the treatment of thrombotic disorders, including pulmonary embolism, deep vein thrombosis and more,” said Desai.

“The molecules we have designed may possess several advantages compared to currently available anticoagulation drugs,” he said.

“For example, new anti-clotting therapies may result in reduced hospital stays for patients, fewer side effects, and possibly an overall cost reduction in therapy because our molecules are likely to be synthesized in an inexpensive manner.”

Desai and his team are now investigating which unit or units in the complex molecule are responsible for the anti-clotting activity.

This work was supported by grants from the National Institutes of Health and the American Heart Association National Center.

Desai collaborated with VCU researchers Brian L. Henry, Bernhard H. Monien; and Paul E. Bock, who is affiliated with Vanderbilt University.

About VCU and the VCU Medical Center: Virginia Commonwealth University is the largest university in Virginia and ranks among the top 100 universities in the country in sponsored research. Located on two downtown campuses in Richmond, VCU enrolls nearly 32,000 students in 205 certificate and degree programs in the arts, sciences and humanities. Sixty-five of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 15 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the nation’s leading academic medical centers. For more, see vcu/.

Source: Sathya Achia-Abraham

Virginia Commonwealth University

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Lower Blood Pressure Linked To Statins

10 01 15'

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An article published in the Archives of Internal Medicine
reports that statins – medications that are usually prescribed to lower
blood cholesterol levels – may also lower blood pressure. Beatrice A.
Golomb, M.D., Ph.D., (University of California, San Diego, La Jolla)
and colleagues noted a modest but significant reduction in blood
pressure for patients taking statins.

Statins are a type of drug that inhibits an enzyme involved in the
synthesis of cholesterol, and thus leads to a decrease in blood
cholesterol levels. Previous research has found that blood pressure may
also be affected by statins, specifically for patients with high blood
pressure (hypertension). It has been hypothesized that statins trigger
compounds that make blood vessels wider, improving their
function.

To test the effect of statins on blood pressure, the researchers
conducted a randomized, double-blind trial with 973 participants who
did now have diabetes or cardiovascular disease. Over a period of six
months between 2000 and 2004, the researchers told 322 participants to
take 20 milligrams of the statin simvastatin, 323 participants to take
40 milligrams of the statin pravastatin, and 328 participants to take
placebo. The statin amounts were taken from usual doses from when they
are prescribed to lower cholesterol. At the beginning of the study, the
researchers took blood pressure measurements of each participant.
Additional measurements were taken after one and six months during the
treatment period, and also two months after ending treatment.

Blood pressure is conventionally reported using two numbers: systolic
(top number) over diastolic (bottom number). The researchers found that
individuals who took the statin had an average decrease of 2.2 mmHg in
systolic blood pressure and an average decrease of 2.4 mmHg in
diastolic pressure. The authors note that, “Blood pressure reductions
ranged from 2.4 to 2.8 milligrams
of mercury for both systolic blood pressure and diastolic blood
pressure with both simvastatin and pravastatin, in those subjects with
full follow-up and without potential for influence by blood pressure
medications (i.e., neither receiving nor meriting blood pressure
medications).”

The authors, however, found that the effect of statins changed over
time. After one month of statin treatment, there was no noticeable
effect on blood pressure. But there was a significant effect after six
months of treatment, and the effect decreased two months after
finishing treatment.

“This study adds to our understanding of the effects of statins,
currently the best-selling prescription drugs in the world,” conclude
the researchers. “The reduction in blood pressure seen with statins may
contribute – among other identified factors – to some of the ‘rapid’
cardiovascular benefits of statins, arising too swiftly to be explained
by effects of statins on plaque accumulation.”

Reduction in Blood Pressure With Statins
Beatrice A. Golomb, MD, PhD; Joel E. Dimsdale, MD; Halbert L. White,
PhD; Janis B. Ritchie, BSN; Michael H. Criqui, MD, MPH
Archives of Internal Medicine (2008). 168[7]:
721 – 727.
Click
Here to View Abstract

: Peter M Crosta

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Irish Government Launches Program To Provide Life Insurance To People With HIV, Hepatitis C Through Contaminated Blood Products

09 30 15'

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The Irish government on Thursday launched a program to provide life insurance, mortgage protection and travel insurance to people who contracted HIV or hepatitis C through contaminated blood products, Ireland’s Evening Echo reports (Evening Echo, 9/27).

In the mid-1980s, about half of Ireland’s 500 hemophiliacs contracted HIV or hepatitis C from the nation’s blood supply. In April 2002, then Irish Health Minister Michael Martin and the Irish Hemophilia Society announced a $90 million deal to compensate hemophiliacs who were infected with HIV from state-provided contaminated blood products (Kaiser Daily HIV/AIDS Report, 4/15/02). According to the Evening Echo, about 3,300 people in Ireland have initiated claims against the government related to infections from contaminated blood products.

People who enroll in the new insurance plan — which is expected to cost about 1.1 billion pounds, or about $2.2 billion — will pay the average premium for an HIV-negative person of the same age and gender, and the government will cover additional costs. Applications for mortgage protection and life insurance will be subject to restrictions after 12 months, the Evening Echo reports (Evening Echo, 9/27).

Eleanor O’Mahony — chair of Positive Action, a group that represents women who acquired HIV or hepatitis C though blood transfusions — said that the insurer Eagle Star is offering the policies and encouraged other insurers to offer policies so that “competition could be stimulated” (O’Sullivan, Irish Examiner, 9/28). The program, which was first announced last year, is the first of its kind worldwide, the Evening Echo reports (Evening Echo, 9/27).

Comments
Positive Action said the program is “long-awaited” and added that the group’s members have been unable to purchase homes because of their medical conditions. Health Minister Mary Harney said the program is an “important measure to provide further support” to people who acquired HIV or other infectious diseases through contaminated blood products. Harney added that the “inability of these people to buy life [insurance] or mortgage protection policies added further problems to the damage they had already suffered.”

John Dwyer, who will administer the program, said it will have a “very positive impact on the lives of those” living with HIV or hepatitis C. “This in effect means that they and their families will now have greater security and peace of mind into the future,” Dwyer added (Irish Examiner, 9/28).

Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

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Genmab Announces Additional Positive Results In HuMax-CD20 CLL Phase I/II Study

09 29 15'

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Genmab A/S (CSE:
GEN) announced today additional positive results in the HuMax-CD20(TM)
(ofatumumab) Phase I/II study to treat patients with relapsed or refractory
chronic lymphocytic leukemia (CLL). An objective response rate of 50% (13
of 26 evaluable patients) was observed in patients treated at the highest
dose level (2000 mg). This included one nodular partial remission (nPR)
confirmed by CT scan and one patient who qualified as nPR but had residual
lymphadenopathy revealed by CT.

Responders include one additional patient compared to previously
reported data.

The median time to disease progression in all patients treated at 2000
mg was approximately 16 weeks ranging from 15 to 23 weeks. In the patients
responding to HuMax-CD20 treatment, the median time to disease progression
was 23 weeks ranging from 20 – 31 weeks. The median time to next anti-CLL
treatment was 52 weeks. These survival endpoints correlated statistically
to the patients’ total exposure to HuMax-CD20 over time and to the
clearance of the antibody.

“The CLL patients in this study appear to have benefited from treatment
with HuMax-CD20. These data strongly support further development of HuMax-
CD20 in CLL,” said Lisa N. Drakeman, Ph.D., Chief Executive Officer at
Genmab.

These results are being presented at poster session #2842 on December
11 from 10:30AM to 7PM local time in Hall E1 West, board 71-III at the 48th
Annual American Society of Hematology Annual Meeting and Exposition in
Orlando, Florida.

About the study

The study is an open-label dose escalation trial that enrolled 33
patients who had failed previous therapy. The trial has three dose levels.
Three patients at the first dose level received an initial dose of 100 mg
followed by three weekly doses of 500 mg; at the second dose level three
patients received a dose of 300 mg followed by three weekly doses of 1,000
mg; and at the third level, 27 patients received an initial dose of 500 mg
followed by three weekly doses of 2,000 mg.

The total follow up period for this study is 12 months from treatment
start and the primary endpoint of the trial is objective response over the
period from screening to week 19. An objective response is one that lasts
at least 8 weeks by the NCI working group guidelines for CLL.

About Genmab A/S

Genmab A/S is a biotechnology company that creates and develops human
antibodies for the treatment of life-threatening and debilitating diseases.
Genmab has numerous products in development to treat cancer, infectious
disease, rheumatoid arthritis and other inflammatory conditions, and
intends to continue assembling a broad portfolio of new therapeutic
products. At present, Genmab has multiple partnerships to gain access to
disease targets and develop novel human antibodies including agreements
with Roche and Amgen. A broad alliance provides Genmab with access to
Medarex, Inc.’s array of proprietary technologies, including the UltiMAb(R)
platform for the rapid creation and development of human antibodies to
virtually any disease target. In addition, Genmab has developed
UniBody(TM), a new proprietary technology that creates a stable, smaller
antibody format. Genmab has operations in Copenhagen, Denmark, Utrecht, the
Netherlands, Princeton, New Jersey, US and Hertfordshire in the United
Kingdom. For more information about Genmab, visit genmab.

This press release 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 product discovery and development,
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 obsolete, and
other factors. Genmab is not under an obligation to update statements
regarding the future following the publication of this release; nor to
confirm such statements in relation to actual results, unless this is
required by law.

Genmab(R); the Y-shaped Genmab logo(R); HuMax(R); HuMax-CD4(R); HuMax-
EGFr(TM); HuMax-Inflam(TM); HuMax-CD20(TM); HuMax-TAC(TM); HuMax-HepC(TM),
HuMax-CD38(TM); and UniBody(TM) are all trademarks of Genmab A/S.
UltiMAb(R) is a trademark of Medarex, Inc.

Genmab A/S
genmab

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Little-Studied Blood Syndrome Gains Researchers’ Attention

09 28 15'

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Motivated by the lack of treatment options for patients with antiphospholipid syndrome (APS), rheumatology researchers convened an international committee to address the problem directly. Their creation, APS ACTION (Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking), is bringing together some of the foremost experts on APS-a little-known blood condition that can cause severe health consequences-to design clinical trials and registries focused on improving patient outcomes.

As a result of its first-ever meeting this past November, APS ACTION determined that distinct variations of APS-which causes frequent abnormal blood clots in arteries and veins -made patient studies into the condition very challenging. Blood clots form because the immune system mistakenly produces antibodies against phospholipid-binding plasma proteins, which puts those affected at risk for stroke and pregnancy complications.

“We concluded there are few controlled clinical trials that have included a heterogeneous group of APS patients who exhibit many different forms of the disease and antiphospholipid antibody test results. Comparison between patients is very difficult when APS looks different from one patient to another,” reported rheumatologist Doruk Erkan, M.D., who is an associate physician-scientist at the Barbara Volcker Center for Women and Rheumatic Disease and clinical co-director of the Mary Kirkland Center for Lupus Care at Hospital for Special Surgery in New York. Dr. Erkan is also the newly-elected Executive Committee Chair of APS ACTION.

Since APS ACTION formed, physicians have been vocal in their determination to advance APS research and treatment and to not be derailed by differences of opinion related to clinical practice.

“I read a post on a Facebook group for APS patients that said, ‘Finally these researchers have started to work together.’ That was sobering,” recalled Dr. Erkan. “While treatment of APS touches on contentious issues, the enthusiasm of APS ACTION participants is palpable. The urgency of the situation calls for a collaborative approach, and we’re working together to improve research, treatment and quality of life for all APS patients.”

The scarcity of comprehensive, well-designed clinical trials involving the condition and its treatment means that evidence-based recommendations to treat APS are hard to come by. In the past, this caused physicians to split into groups that emphasized different treatment regimens. But, it also inspired the creation of APS ACTION.

Emboldened by the newfound consensus of rheumatologists who often differ in their treatment recommendations for individuals with APS, a number of subcommittees have already taken up the challenge to address long-standing issues in APS research.

“The subcommittees have eagerly started to address clinical trial design, an APS patient registry, APS research and outreach to advocacy groups,” said rheumatologist Michael Lockshin, M.D., director of the Barbara Volcker Center for Women and Rheumatic Disease and also co-head of the Mary Kirkland Center for Lupus Research, both at Hospital for Special Surgery. Dr. Lockshin is also one of the executive committee members of APS ACTION.

Dr. Lockshin heads a subcommittee tasked with exploring funding options for maintaining the infrastructure of this international consortium and developing a comprehensive patient registry. “APS ACTION hit the ground running, and we want to keep up this enthusiasm by moving ahead on all APS research-related issues. Members of APS ACTION are dedicated to standardizing clinical care and research and developing evidence-based treatment recommendations, ultimately improving patient outcomes.”

About APS ACTION

Twenty-seven physicians from 19 international centers currently participate in APS ACTION. The number of centers is expected to increase when the infrastructure is finalized.

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Hospital for Special Surgery

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