Ipsen (Euronext : FR0010259150; IPN) and Inspiration Biopharmaceuticals, Inc. (Inspiration) announced that the Committee for Orphan Medicinal Products of the European Medicines Agency has issued a positive opinion on the granting of orphan drug status for OBI-1 for the treatment of hemophilia. Final adoption of the opinion is expected from the European Commission later this year and subject to it being finally granted, the orphan drug status would trigger a 10-year market exclusivity to OBI-1 in the European Union after its marketing approval. The FDA also issued an Orphan Drug Designation for OBI-1 in March 2004.

Jean-Luc Bélingard, Chairman and Chief Executive Officer of Ipsen said: “Our transaction with Inspiration in late January of this year expresses Ipsen’s long term strategy to create a world leading hemophilia franchise. We are honored that the Committee for Orphan Medicinal Products of the European Medicines Agency shares our view of the medical benefit provided by OBI-1 to the hemophilia community.”

John Taylor, Co-Founder and Chairman of Inspiration added: “We are pleased with the continued progress of OBI-1 as a new, innovative therapy in the treatment of unmet medical needs in hemophilia.”

About Hemophilia

Hemophilia, congenital or acquired, is a bleeding disorder caused by low levels or absence of a protein called a coagulation factor, essential for blood clotting. The two most common forms of hemophilia are types A and B. Hemophilia A is caused by a factor VIII deficiency and occurs in ~1 out of every 5,000 male births. Hemophilia B is caused by factor IX deficiency and occurs in ~1 out of every 30,000 male births. Approximately 60% of persons with hemophilia have a severe condition, which results in frequent spontaneous bleeding episodes in addition to serious bleeding after injuries. The market for hemophilia treatment is 7.5 billion dollars annually.

About OBI-1

About a third of patients with congenital hemophilia A and patients with acquired hemophilia develop an immune reaction to human forms of FVIII (hFVIII) and can no longer respond to human Factor VIII. Since OBI-1 possesses low cross reactivity to anti-hFVIII antibodies, it is expected that OBI-1 can provide therapeutic benefits to patients who are not able to use hFVIII.

OBI-1, a recombinant B-domain deleted FVIII bioengineered for low cross reactivity to anti-human FVIII inhibitors based on the porcine amino acid sequence, has recently been tested in a Phase II trial. OBI-1 was administered to patients with congenital hemophilia A complicated by the presence of human FVIII inhibitors experiencing a non-life/non-limb threatening bleed. A total of 25 bleeding episodes in 9 patients were treated with OBI-1, and all were successfully controlled. One subject had a mild infusion reaction and when re-treated for a subsequent bleed the subject did not report any adverse event. Eight out of nine (89%) subjects developed anti-pFVIII antibodies following exposure to OBI-1 and in subjects receiving repeated OBI-1 treatment higher anti-pFVIII titres did not affect efficacy or safety. The study demonstrated that OBI-1 is well-tolerated and can be given as a short infusion. OBI-1 is expected to enter phase III in 2010.

Inspiration Biopharmaceuticals

analyses from the largest initial registration clinical trial program ever
undertaken in the renal anemia arena provide efficacy and safety
information on the investigational anemia therapy MIRCERA(TM) for the
treatment of renal anemia associated with chronic kidney disease (CKD) in
patients on dialysis and not on dialysis. Three data analyses were
presented at the National Kidney Foundation 2007 Spring Clinical Meetings
in Orlando, Florida.

According to these analyses, MIRCERA with extended dosing up to once
every four weeks: (1) corrected and maintained hemoglobin (Hb) levels in
patients with CKD, on dialysis and not on dialysis; (2) maintained Hb
levels in dialysis patients, regardless of congestive heart failure (CHF)
status as shown in a post-hoc analysis; and (3) exhibited a safety profile
that is consistent with that of commercially available erythropoiesis
stimulating agents (ESAs) and typical of those associated with this patient

“The goal in treating renal anemia is to safely maintain target
hemoglobin levels,” said Steven Fishbane, MD, Associate Director of
Nephrology, Associate Chairman of the Department of Medicine, and Director
of End-Stage Renal Disease research at Winthrop University Hospital. “These
data analyses clearly demonstrate that MIRCERA corrected low hemoglobin
levels, and maintained target hemoglobin levels with the added convenience
of up to once- monthly dosing.”

About the Studies

Safety and Tolerability of C.E.R.A. In Patients With Chronic Kidney
Disease: Pooled Data From Ten Phase II-III Trials

Pooled data from four Phase II and six Phase III studies evaluated the
safety and tolerability of MIRCERA (intravenous (IV) and subcutaneous (SC))
in patients not previously treated with commercially available ESAs and
those previously treated with commercially available ESAs. This data
analysis showed that the incidence of adverse events in the Phase II and
III safety population was similar between MIRCERA and reference groups, and
typical of those associated with this patient population; and the
administration of MIRCERA for the treatment of anemia associated with CKD
has a safety profile consistent with that of reference ESAs.

C.E.R.A. Once Monthly Maintains Stable Hemoglobin Levels In Patients
With Chronic Kidney Disease on Dialysis With and Without Congestive Heart
Failure (CHF)

This retrospective analysis of two Phase III studies evaluated the
efficacy and tolerability of MIRCERA (IV and SC) administered once every
two weeks or once every four weeks in patients with or without congestive
heart failure who were on dialysis and were directly converted from epoetin
alfa or beta. The post-hoc analysis showed that MIRCERA, administered at
extended dosing intervals, was effective in maintaining stable Hb levels in
dialysis patients with and without CHF who were directly switched from
shorter-acting ESAs.

Efficacy of C.E.R.A. in Treatment of Renal Anemia: Overview of 6 Global
Phase III Trials

This was an overview of six global studies in approximately 2,400
patients that compared MIRCERA with epoetin alfa or beta and with
darbepoetin alfa. This overview showed that the efficacy of MIRCERA was
comparable to that of the comparator agents, but required less frequent

Chronic Kidney Disease and Renal Anemia

According to the National Kidney Foundation, 20 million Americans have
chronic kidney disease and another 20 million are at increased risk for the
condition. CKD is considered a rising global epidemic because it is linked
to two of the fastest-growing diseases – diabetes and hypertension. An
often under-diagnosed condition, CKD is called a disease multiplier because
many of its risk factors are also complications of the disease itself,
creating a relentless spiral in which one condition can lead to the
exacerbation of the other and, ultimately, to death. In particular, renal
anemia, diabetes and cardiovascular disease frequently play this double


The initial registration clinical program for MIRCERA consisted of 10
global studies involving more than 2,700 patients from 29 countries. The
Phase III program for MIRCERA consisted of two correction and four
maintenance studies exploring intravenous and subcutaneous MIRCERA at
extended administration intervals.

Roche filed applications with the regulatory authorities in the United
States and in the European Union in April 2006 seeking approval for the use
in the treatment of anemia associated with CKD in patients on dialysis and
not on dialysis.

Safety Information

MIRCERA has a demonstrated safety profile comparable to other
erythropoietic agents.

The most commonly reported adverse events in the MIRCERA Phase II/III
clinical program were hypertension, nasopharyngitis and diarrhea.
Erythropoietic therapies increase the risk of death and serious
cardiovascular events when administered to a hemoglobin of greater than 12

Erythropoiesis stimulating agents, when administered to target a
hemoglobin of greater than 12 g/dL have shortened the time to tumor
progression, shortened survival and increased the risk of death in cancer

Pure Red Cell Aplasia (PRCA) has been observed in patients treated with
erythropoietin therapy. However, PRCA has not been observed with MIRCERA in
clinical trials to date.

About Roche

Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S.
pharmaceuticals headquarters of the Roche Group, one of the world’s leading
research-oriented healthcare groups with core businesses in pharmaceuticals
and diagnostics. For more than 100 years, the Roche Group has been
committed to developing innovative products and services that address
prevention, diagnosis and treatment of diseases, thus enhancing people’s
health and quality of life. An employer of choice, in 2006, Roche was named
one of the Top 20 Employers (Science magazine), ranked the No. 1 Company to
Sell For (Selling Power), and one of AARP’s Top -Companies for Older
Workers, and in 2005, Roche was named one of Fortune magazine’s Best
Companies to Work For in America. For additional information about the U.S. pharmaceuticals
business, visit our websites: rocheusa or roche.us.

All trademarks used or mentioned in this release are protected by law.


View drug information on Mircera.

Pharmacogenomics offers the promise of individualized drug therapies based on a patient’s genetic make-up and that of the tumor cells. Such tailor-made drug regimes hold the promise to further increase survival rates for cancer. They could also decrease the sometimes lethal side effects of the powerful drugs used in cancer therapy, experts reported at the 12th Congress of the European Hematology Association in Vienna.

The role of pharmacogenomics in the treatment of childhood acute lymphoblastic leukemia (ALL) was addressed today by Dr Leo Kager from St Anna Children’s Hospital in Vienna at the European Hematology Association congress in Vienna (Austria) from 7 to 10 June 2007. Pharmacogenomics is a new technique for investigating the influence of variations in genetic make-up on an individual’s response to a particular drug. Tests are carried out on patients’ blood or bone marrow cells to look at the expression of genes which affect drug metabolism and activity. These laboratory tests are then correlated with the actual response of patients to the same drugs both with respect to effectiveness and toxicty.

Dr Kager says he has seen patients die because of toxic reactions to drugs used in leukemia treatments. In those patients where severe toxicity is exhibited, reactions can include such consequences as convulsions, severe infections or bleeding due to hemato-toxicity, liver failure, thrombosis, and mucositis.

Toxic drug reactions are very individual. For example, 1 in 300 people may have a severe toxic reaction to a drug, while 10 percent of a sample of patients may exhibit low toxic reactions and 90% full tolerance of the same medication. “The great difficulty for physicians is that they must prescribe medication without being able to assess which patient will response with severe toxic reactions”, Dr Kager says.

Genetic tests to prevent toxicity

Pharmacogenomics effectively means it may be possible to develop genetic tests that utilize a patient’s genetic profile to prevent toxicity. Simple as this may sound, Dr Kager says the difficulties should not be minimized: “Estimating appropriate drug dosages is a complicating factor. Administering too little of a drug can be dangerous, if poor results are achieved in the tumor cells targeted. What doctors need to know is what a particular drug will do in tumor cells.”

The latest research in pharmacogenomics examines the genetics of both normal and tumor cells, addressing the need to balance requirements to protect healthy tissue as much as possible while destroying the tumor.

At the moment, ALL patients are stratified according to certain risk factors (e.g., age, cytogenetic changes in tumor cells, in vivo response to chemotherapy) to receive either very intensive treatment (so called ‘high-risk’ patients, which means based on their prognostic factors these patients have a high risk of relapse), or less intensive treatment (standard risk and low risk patients). Within a risk group all patients receive the same course of treatment of drugs, at the same dosage. It has been established empirically that these dosages represent the range of best available treatment. Dr Kager: “But this is clearly not the best for each individual patient, as is amply demonstrated by the fact that in patients with a high risk ALL, many patients survive, while in patients with a low risk ALL, a few patients die. The fact is that a patient may die because too low or too high dose of these very powerful drugs is administered.” In treating childhood ALL, a physician is normally working with a range of up to eight different drugs. Childhood ALL remains a rare disease, fortunately. But there is a slight increase in incidence.

Promising approach to tailor therapy

Pharmacogenomics is of course relevant beyond the treatment of leukemia. Good success has already been achieved in the treatment of gastro-intestinal tumors. In fact these methods to assess drug effectiveness and toxicity begin to be applied in all fields. As a further example of the growing importance of pharmacogenomics, essential literature on hematology increasingly dedicates space to the field. In the use of oral anti-coagulants in treatment of thrombosis patients, which affects vastly more patients than leukemia, pharmacogenomics is a promising approach to tailor therapy.

Front line research being conducted at the moment in pharmacogenomics has shown that cellular pathways targeted by antileukemic medications differ considerably in ALL subtypes. A powerful tool to analyze the expression of thousands of genes in one experiment are microarray gene chips. In such experiments, the expression of about 20,000 genes can be measured, and ground breaking work testing patients samples and cell lines is being done to ascertain the interplay between a drug and particular genes to understand better why some leukemia patients are resistant, for example, to cortisone treatment.

Dr Kager: “While pharmacogenomics won’t perhaps explain all differences in individual patient reactions to drugs it can certainly further improve a physician’s ability to accurately prescribe.”

Porzellangasse 35

Doctors at Children’s National Medical Center have found that carbon monoxide levels in the blood of young children increase during routine general anesthesia. Anesthesiologists have found for the first time that, under certain circumstances, infants and children may be exposed to carbon monoxide during routine anesthesia resulting in a rise in the carbon monoxide levels in the child’s blood.

Because carbon monoxide can be generated as a byproduct of anesthesia, anesthesiologists world-wide use specific precautions to prevent and limit its production, according to Richard J. Levy, MD, Chief of Cardiac Anesthesiology, at Children’s National. Dr. Levy’s team identified the conditions in which carbon monoxide may be inhaled during anesthesia:
The first study demonstrated that carbon monoxide detected in the breathing circuit correlated with the increase in blood levels in children 2 years and older. The study included 15 patients between 4 months and 8 years.

The second study identified that the patient’s own exhaled carbon monoxide may be “re-breathed” during low-flow anesthesia – the current standard of care – where fresh gas flows more slowly into the circuit, rather than rapidly.

“The main goal is to provide the safest environment for young patients who require surgery,” said Dr. Levy. “We have identified tangible ways to reduce the risk of carbon monoxide exposure, and our hope is that these changes will be implemented internationally.”

Much remains unknown about the effects of low-dose carbon monoxide exposure on the developing brain. Several recent studies have suggested there may be a link to hearing impairments. Though there is more research to be done to determine these impacts, Dr. Levy recommends two immediate changes that will eliminate the risk of carbon monoxide exposure in children:
In the anesthesia machine, use carbon dioxide absorbents that lack strong metal alkali and do not degrade inhaled anesthetics (avoids CO production risk)

Avoid of low-flow anesthesia (avoids CO re-breathing risk)

Following Dr. Levy’s study findings, Children’s National switched to the recommended absorbent to minimize the risk to patients. Although the sample size is small, the results are compelling and Dr. Levy believes changes should be implemented.

Dr. Levy’s research has been named the top study out of 600 at the International Anesthesia Research Society 2010 meeting, and won the John J. Downes Research Award for best abstract at the upcoming Society of Pediatric Anesthesia/American Academy of Pediatrics 2010 Annual meeting.

Emily Dammeyer
Children’s National Medical Center

Orcrist Bio Inc. (ORC) a biotech company developing stem cell-mobilizing
pharmaceuticals, announced today that it has filed with the European
Competent Authority in Seville, Spain, a Phase I, open-label,
single-ascending-dose, safety study of HYC750 in healthy male volunteers. The
goal of the study is to assess the safety, tolerability, pharmacokinetics and
pharmacodynamics (induction of hematopoiesis) of HYC750, a patent-protected
formulation of hyaluronan. ORC utilized the regulatory expertise and
experience of Kinesis Pharma BV (Breda, Netherlands) to develop the clinical
trial submission. The planned study is to be conducted by InPEC BV (Breda,
Netherlands) at their clinical trial site in Malaga, Spain.

Dr. Thomas Ichim, Chairman of ORC’s Scientific Advisory Board commented,
“HYC750 possesses a very favourable pharmacological and pharmaceutical
profile and is an excellent candidate for aggressive and rapid clinical

“Filing the requisite regulatory documentation with the European
authorities to initiate our Phase I clinical trial was a major accomplishment
for our company and represents Orcrist’s most important milestone thus far,”
said Dr. Brett Schönekess, President and CEO of Orcrist. “We are thrilled
with the expertise and professionalism provided by both Kinesis and InPEC,
and are very excited to see the HYC750 clinical program move forward. Our
clinical goal is to confirm the safety profile of HYC750 and to see a clear
illustration of its stem cell mobilization properties, which would support
its future development as a treatment for chemotherapy-related blood cell

“We are very honored to be chosen by Orcrist to coordinate and perform
their Phase I study with HYC750 and we look forward to the future initiation
of the trial,” commented Dr. Ronald van der Geest, Chief Business Officer of
InPEC BV. “Orcrist, Kinesis, and InPEC have worked as a team on this project,
and I believe a very strong clinical trial application has been submitted.”

About Orcrist Bio Inc.

Orcrist Bio Inc. is a biotechnology company dedicated to developing and
commercializing promising therapeutics for areas in which a clear market
opportunity exists. ORC’s lead program revolves around HYC750, a novel stem
cell mobilizer compound that promotes the egress of stem cells and other
blood cells from the bone marrow into the blood, from which they can be
harvested and applied toward treating chemotherapy-related white blood cell
depletion. Orcrist is actively looking to add to its pipeline exploring the
innate properties of HYC750 and its effects on stem cells, as well as through
in-licensing opportunities of other products with clear market potential. ORC
is located in Calgary, Alberta. The company is financed by its founders and
by private investors.

About Kinesis Pharma BV

Kinesis Pharma BV is an independent, privately owned company based in The
Netherlands. Kinesis aims to facilitate a fast and high quality drug
development process in close collaboration with the preclinical and clinical
R&D departments of pharmaceutical and biotech companies through consultancy
and contract research services. Currently, Kinesis employs about 55 people,
many of them with extensive industrial and/or regulatory experience.

About InPEC BV

InPEC BV is a clinical CRO that focuses on the execution of Phase I and
IIa clinical trials. Its professional and experienced team, and state of the
art facilities, embedded within the care of a private hospital with an ICU
unit on the same floor, guarantee maximum safety for the full range of
clinical pharmacology studies. Electronic data processing procedures are in
place to enable high-quality and efficient data processing on-site. InPEC’s
head office is located in the Netherlands. Clinical facilities are located in
Malaga, Spain.

Orcrist Bio Inc.

Virginia Commonwealth University researchers studying hemoglobin genes, mutations of which play a role in genetic blood disorders like sickle cell anemia and beta-thalassemia, have identified two proteins that are responsible for regulating overlapping groups of genes during the development of red blood cells.

The findings may point researchers to future gene therapies for patients with sickle cell anemia and beta-thalassemia.

In an article pre-published online as a First Edition Paper in the journal Blood, the journal of the American Association for Hematology, researchers reported that a protein called KLF2 coordinates with a related and well-studied transcription factor, EKLF, in the regulation of embryonic globin genes responsible for the development of mouse embryonic red blood cells.

EKLF plays a central role in the developmental regulation of the adult beta-globin gene, and is essential for the maturation and stability of adult red blood cells. KLF2 is a protein crucial for making embryonic red blood cells.

“If EKLF and KLF2 can turn on the embryonic globin genes in adult cells — we don’t know if this is true yet — then these findings may provide a gene therapy approach for treating sickle cell anemia and beta-thalassemia. It is well-established that the expression of embryonic globin genes can help ameliorate these diseases,” said Joyce A. Lloyd, Ph.D., associate professor of human genetics at the VCU Massey Cancer Center, and corresponding author for this study.

Lloyd’s team studied gene expression and red blood cell development in the mouse embryo. They used mouse embryos missing both the KLF2 and EKLF genes to show that embryonic globin expression is severely reduced, and that the embryos therefore are anemic, compared to mice missing KLF2 or EKLF alone.

“This likely means that EKLF and KLF2, which are related transcription factors, regulate overlapping groups of genes in developing red blood cells. In the absence of both factors, they cannot compensate for each other, causing more serious defects in red blood cell development,” Lloyd said.

According to Lloyd, the production of blood cells involves a complex differentiation pathway with interactions between many molecular players and proteins.

In humans, there are four globin genes clustered on chromosome 11 in the order in which they are ‘turned on’ or expressed. These genes include the epsilon-globin gene, two gamma-globin genes and the beta-globin gene. Lloyd said that during fetal development, the embryonic epsilon-globin gene is active first, followed by the gamma-globin genes, and finally the adult form, beta-globin takes control following birth.

Understanding how genes are regulated or turned on and off is critical. In gene therapy, a normal gene can be inserted into cells to correct a genetic defect. However, according to Lloyd, in this case, the goal would be to insert a transcription factor into adult cells that would turn on an existing, silenced embryonic gene.

This research was supported by a grant from the National Institutes of Health.

Lloyd collaborated with Jack Haar, Ph.D., professor of anatomy and neurobiology in the VCU School of Medicine; Priyadarshi Basu, Ph.D., a former postdoctoral fellow at VCU; and Tina Lung, who recently earned her masters degree. Additionally, colleagues from the Department of Molecular Genetics, Biochemistry and Microbiology at the University of Cincinnati also contributed to this work.

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 more than 30,000 students in nearly 200 certificate and degree programs in the arts, sciences and humanities. Sixty-three 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/.

About the VCU Massey Cancer Center: The VCU Massey Cancer Center is one of 61 National Cancer Institute-designated institutions that leads and shapes America’s cancer research efforts. Working with all kinds of cancers, the Center conducts basic, translational and clinical cancer research, provides state-of-the-art treatments and clinical trials, and promotes cancer prevention and education. Since 1974, Massey has served as an internationally recognized center of excellence. It offers more clinical trials than any other institution in Virginia, serving patients in Richmond and in four satellite locations. Its 1,000 researchers, clinicians and staff members are dedicated to improving the quality of human life by developing and delivering effective means to prevent, control and ultimately to cure cancer. Visit Massey online at massey.vcu/.

Source: Sathya Achia-Abraham

Virginia Commonwealth University

The use of recombinant activated factor 7 (rFVIIa) despite its potential for adverse events displays the serious shortcomings of Canada’s current drug surveillance system, according to a commentary published in CMAJ (Canadian Medical Association Journal) .

Off-label use of this therapy – a blood product – was driven by key physician opinion leaders who thought recombinant factor VIIa could be used to treat or prevent bleeding in patients without hemophilia at risk of death. This shows how promising case reports can change practice prematurely before more data is available.

Use of recombinant factor VIIa in patients without hemophilia is expensive, marginally effective and risky.

“Off-label use of drugs can be beneficial, however, without a process for ongoing evaluation, deaths, disabilities and costs may be accruing without being obvious at the bedside,” writes Paul Hébert, Editor-in-Chief, CMAJ, with coauthors. “With recombinant factor VIIa, physicians were too eager to believe the anecdotes and did not push for the appropriate studies.”

Monitoring drug use as well as safety is complicated and lacks a simple solution, although several changes should be considered. These include improved collaboration between payers and insurers who approve and track usage as well as manufacturers, prioritizing higher risk drugs in an improved drug surveillance system, better evaluation of new drugs and greater surveillance powers for regulatory bodies.

Source: CMAJ (Canadian Medical Association Journal)

The development of the targeted
anticancer medicine imatinib has been a landmark event in the treatment of
patients with chronic myeloid leukemia (CML), a cancer of the bone marrow.
However, over time, the cancer can become resistant to this treatment,
usually because of mutations in the protein that imatinib targets. Two
studies being presented today at the 48th Annual Meeting of the American
Society of Hematology (ASH(TM)) highlight new compounds in development that
can effectively treat CML when imatinib is no longer effective.

“This is important progress for patients who relapse on imatinib
therapy,” said Charles A. Linker, MD, University of California, San
Francisco. “Not only does this research show the efficacy of new treatments
for imatinib- resistant disease, it also demonstrates the value of looking
at each patient’s mutation pattern to determine an individual course of

Hematologic and Cytogenetic Response Dynamics to Nilotinib (AMN 107)
Depend on the Type of BCR-ABL Mutations in Patients with Chronic
Myelogenous Leukemia (CML) after Imatinib Failure [Abstract #749]

Treatment with imatinib has allowed patients with chronic myelogenous
leukemia (CML) to experience a nearly 90 percent five-year survival rate,
as the drug blocks the tyrosine kinase BCR-ABL, an abnormal protein driving
the overproduction of abnormal white blood cells characteristic of
leukemia. However, many patients have eventually developed resistance to
this treatment because their cancer cells are able to mutate and adapt,
causing their disease to relapse.

Researchers studied nilotinib, a novel treatment that blocks the
BCR-ABL protein, to determine its effectiveness among patients for whom
imatinib has stopped working. In vitro work showed effectiveness even in
patients developing BCR-ABL mutations associated with resistance to
imatinib. Investigators looked at blood samples from 101 CML patients, 64
of whom were in the early or chronic phase, 22 in the later or accelerated
phase, and 15 in the final or blast crisis phase of the disease, and
screened for the BCR-ABL gene mutation that signals CML.

Prior to treatment with nilotinib, researchers found 28 different
BCR-ABL mutations in 61 patients. Of this group, nine showed two mutations,
three showed three mutations, and one patient showed four mutations. When
treated with nilotinib twice a day (400 mg), 70 percent of patients with
mutations experienced a hematologic response, with the highest rate of
response seen in patients in the chronic phase (78 percent), followed by
accelerated phase (75 percent) and blast crisis (25 percent). Patients
without mutations responded even better to the therapy, as 88 percent
experienced a hematologic response rate.

Chronic phase patients whose genetic mutations had shown sensitivity to
nilotinib in the lab achieved a complete cytogenetic response within three
to six months. Two patients with the BCR-ABL mutation T315I — a mutation
highly resistant to both imatinib and nilotinib in the lab — showed no
signs of relapse of disease after one month and 11 months of treatment with
nilotinib, respectively.

“This preliminary data suggests that nilotinib may help patients for
whom imatinib has stopped working by overcoming the gene mutations that
cause imatinib resistance,” said Andreas Hochhaus, MD, of the Medical
Faculty Mannheim of the University of Heidelberg, Germany. “It also shows
the importance of determining each patient’s specific gene mutation, to
apply individualized dosage of nilotinib according to the mutation

Response to Dasatinib after Imatinib Failure According to Type of
Preexisting BCR-ABL Mutations [Abstract #748]

Dasatinib blocks the production of BCR-ABL and it has been shown to
treat CML and ALL that have become resistant to the standard therapy of

This study looked at the type of gene mutations that are more
responsive to treatment with dasatinib to confirm the best targets for
future therapy. Blood samples from 394 patients being treated with
dasatinib (198 chronic phase, 78 accelerated phase, 53 myeloid blast
crisis, and 65 lymphoid blast crisis/ALL) were monitored in three month
intervals to determine how the preexisting genetic mutations responded to
the therapy and if new mutations emerged. Prior to treatment, 46 different
BCR-ABL mutations were detected in 202 patients — 162 patients showed one,
33 patients showed two, six patients showed three, and one patient showed
four mutations.

Patients with mutations responded well to therapy, as complete
hematologic response was achieved in 91 percent of chronic phase patients,
62 percent of accelerated phase patients, 41 percent of myeloid blast
crisis patients, and 34 percent of lymphoid blast crisis/ALL patients.
Complete cytogenetic responses were similar and occurred in 37 percent of
chronic phase patients, 27 percent of accelerated phase patients, 28
percent of myeloid blast crisis patients, and 51 percent of lymphoid blast
crisis patients.

Researchers observed two response patterns in studying treatment with
dasatinib: some patients experienced a decrease in the BCR-ABL expression
and the proportion of the mutated clone simultaneously, while others
experienced a decrease in BCR-ABL followed by a decrease of the mutated
clone after a delay of four to six months. Five patients developed new
mutations associated with resistance to dasatinib, including T315I. The
T315I mutation is highly resistant to both imatinib and dasatinib.

“Dasatinib is an excellent treatment option for patients who have
become resistant to imatinib,” said lead researcher, Martin C. Muller, MD,
Medical Faculty Mannheim of the University of Heidelberg, Germany.
“However, we noted that response depended heavily on the type of genetic
mutation, which may signal a method for individualizing each patient’s

The American Society of Hematology (hematology) is the
world’s largest professional society concerned with the causes and
treatment of blood disorders. Its mission is to further the understanding,
diagnosis, treatment, and prevention of disorders affecting blood, bone
marrow, and the immunologic, hemostatic, and vascular systems, by promoting
research, clinical care, education, training, and advocacy in hematology.

American Society of Hematology

Artisan Pharma, Inc., a private biopharmaceutical company dedicated to bringing best-in-class critical care therapeutics to patients, announced the completion of patient enrollment in its Phase 2b study of ART-123 (Recomodulin® – recombinant human thrombomodulin) in sepsis patients with disseminated intravascular coagulation (DIC). The clinical trial was a randomized, double-blind, placebo-controlled Phase 2b study to assess the safety and efficacy of ART-123 in patients with sepsis and DIC. The clinical study enrolled 750 patients in over 150 sites worldwide.

“DIC in sepsis is a severe condition with a very poor prognosis for patients,” stated Dr. Inder Kaul, M.D., M.P.H., Chief Medical Officer of Artisan Pharma. “We are energized at having reached this milestone and now will be focusing on preparing to analyze the results, which are highly anticipated by the medical and scientific communities.”

“We are very pleased to have achieved this important milestone for Artisan and expect to report the results later this year,” commented Dr. Gary T. Shearman, Executive Chairman.

About ART-123

ART-123 is a novel, recombinant, soluble thrombomodulin for the treatment of DIC (disseminated intravascular coagulation) in sepsis. ART-123 uniquely targets both anti-coagulant and systemic anti-inflammatory pathways, and holds great promise as a self-regulating treatment of DIC in sepsis. Artisan licensed ART-123 from Asahi Kasei Pharma Corporation and holds all development and commercial rights for ART-123 outside of Japan, China, Taiwan and Korea. ART-123 is approved for marketing in Japan for the treatment of DIC.

About DIC in Sepsis

Almost 2 million patients in the United States and Europe suffer from sepsis annually, with up to 30% of them developing or being at high risk of developing DIC. For those that do, prognosis is poor. DIC is a severe condition in which widespread microthrombi formation ultimately contributes to organ dysfunction and death. This market is estimated at over $2 billion and is increasing due to the growing incidence of sepsis in the industrialized world.

Artisan Pharma, Inc.

CaridianBCT, a leading global provider of technology, products and services in automated blood collections, therapeutic systems, whole blood processes and pathogen reduction technologies, announced today it has signed a multi-year agreement with the American Red Cross to continue the use of its automated blood collection technology in American Red Cross Blood centers throughout the United States.

For over 50 years, the American Red Cross has been a primary supplier of life-saving blood and blood products in the U.S. Through its Biomedical Services division, the American Red Cross collects and distributes nearly half of the U.S. blood supply, collecting over 6 million units of blood from nearly 4 million blood donors annually.

“The relationship between the American Red Cross and CaridianBCT is reflective of our combined passion to meet the ever-increasing patient needs for safe, critical blood components,” said American Red Cross Biomedical Services Executive Vice President J. Chris Hrouda. “Under this agreement, we will continue to use CaridianBCT’s Trima Accel® system for the greater collection flexibility.”

The increasing demand for blood components and testing standards, as well as the decreasing donor availability, has heightened the need for blood centers to maximize the ability of every eligible donor to donate the specific blood components required to meet patient needs – a critical factor in ensuring a sufficient, safe blood supply. The Trima Accel system enables blood centers to collect multiple component combinations of leukoreduced, ready-to-store red cells – including double red cells – platelets and plasma, from a single donor, in a single donation.

“We have been extremely pleased with the close working relationship between CaridianBCT and the American Red Cross,” said CaridianBCT President and Chief Executive Officer David B. Perez. “Together, we strive to enhance the productivity capabilities of our Trima technology to collect more of the right blood components, exactly when they are needed to better serve patients, who are the ultimate beneficiaries of the life-saving gift of blood. Our people, products and processes are very much aligned with the goals and objectives of the American Red Cross and the working relationship we have with the American Red Cross allows us to live out our vision, For Better Blood and Better Lives, every day.”

About CaridianBCT:

CaridianBCT, Inc. improves lives through innovation, quality and services delivered by its people, products and processes in blood component technology. It is a leading global provider of technology, products and services in automated blood collections, therapeutic systems, whole blood processes and pathogen reduction technologies – serving blood banks, hospitals and clinical and biotech research facilities. Headquartered in Lakewood, CO, the company has global operations in 32 countries and employs approximately 2500 people. For more information, visit caridianbct.

About the American Red Cross:

The American Red Cross shelters, feeds and counsels victims of disasters; provides nearly half of the nation’s blood supply; teaches lifesaving skills; and supports military members and their families. The Red Cross is a charitable organization – not a government agency – and depends on volunteers and the generosity of the American public to perform its humanitarian mission. For more information, please visit redcross or join our blog at redcrosschat.

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