VOLUME 31 ISSUE 9 ... EDITOR: KEITH BERMAN ... ISSN 0742-7719

EDITOR: KEITH BERMAN
ISSN 0742-7719
PUBLISHER: PATRICK ROBERT
Published by: The Marketing Research Bureau, Inc. 284 Racebrook Rd. Orange, CT 06477
VOLUME 31 ISSUE 9
APRIL 2014
BUSINESS BRIEFS
121
BLOOD & BIOTECHNOLOGY
125
RESEARCH & DEVELOPMENT
127
PLASMA FRACTIONATION NOTES
129
PRODUCT SAFETY UPDATE
130
NEW PRODUCTS
131
RECENT U.S. PATENTS
132
MEETINGS / SUBSCRIPTION FORM
135
____________________COMPANIES IN THIS ISSUE__________________
AMBRX
AMGEN
ASFA
Asklepios BioPharmaceutical
BAXTER HEALTHCARE S.A.
BAXTER INTERNATIONAL
BIOGEN IDEC
BLOOD CENTERS OF AMERICA
bluebird bio
CANADIAN BLOOD SERVICES
CANADIAN PLASMA RESOURCES
CARLYLE GROUP
CERUS
CHATHAM THERAPEUTICS
CORD BLOOD REGISTRY
DATABEAN
ELUSYS THERAPEUTICS
eMAX Health Systems
EUROPEAN HEMOPHILIA CONSORTIUM
EXCELIMUNE
GREEN CROSS
GRIFOLS
GRIFOLS THERAPEUTICS
GSABC COOPERATIVE CORPORATION
Héma-Québec
JAPANESE RED CROSS
JOHNSON & JOHNSON
INVESTISSEMENT QUÉBEC
KAMADA
KEDRION GROUP
NEKTAR THERAPEUTICS
NOVO NORDISK
OCTAPHARMA
ORTHO-CLINICAL DIAGNOSTICS
PLAZMAFEREZIS ALLOMAS Kft
PPTA
PROCHON BIOTECH
SEKISUI MEDICAL
SWEDISH ORPHAN BIOVITRUM
Notice: International Blood/Plasma News© is Protected by Copyright Law. Reproduction or
Photocopy of Any Part Without The Publisher‘s Permission is Prohibited by Law.
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BUSINESS BRIEFS
*
OCTAPHARMA has reported a 26% growth in net sales for 2013, to €1.154 billion ($1.59
billion) from €915.6 million ($1.26 billion) in 2012. Operating income moved up more than
9% from €148 million in 2012 to €162 million last year. The company continues to expand
research and development activity (+24.6% to €45.8 million) and selling and marketing budget
(+9.5% to €74.1 million). Capital expenditures and investment in new activities rose modestly
to €65.5 million, from €60.9 million in 2012.
Strong growth in cash flow, from €131.6 million in 2012 to €205.6 million in 2013, is reflected
in Octapharma’s cash position: from €32.1 million in 2012 to €148.6 million in 2013. The
company’s year-end headcount has continued to climb, reaching 5,514 employees in 2013;
1,000 employees have been added to the Octapharma payroll since year-end 2011.
*
KEDRION GROUP successfully completed the issuance of senior, unsecured and unrated bonds valued at €300 million ($415 million), due in April 2019. These fixed-rate
bonds, which will be listed on the Irish Stock Exchange, bear a 4.625% yearly coupon. The
transaction, announced at the end of a three-day European road show through London, Paris
and Milan, was “received remarkably well by the international financial community and was
finally subscribed by over 140 different categories of investors, with a demand that was three
times greater than the amount of the bonds on offer,” according to a Kedrion news release.
The family-owned company, in which Italy’s national investment fund (the Fondo Strategico
Italiano) also holds a 19% stake, will use proceeds from the issuance of these bonds to fully
repay the Groups current debt and to fund development plans over the next five years. BANKA
IMI SpA and NATIXIS acted as joint lead managers and joint book-runners in the placement
of these bonds.
*
Three Hungarian plasma collection centers operated by PLAZMAFEREZIS ALLOMAS
Kft, a member operating within the KEDRION group of companies, have been awarded
International Quality Plasma Program (IQPP) certification by the PLASMA PROTEIN
THERAPEUTICS ASSOCIATION. The three centers – two in Budapest and one in Debrecen – are the first in Hungary to receive IQPP certification, a process involving rigorous
inspection by an independent third party to ensure compliance with voluntary standards that
ensure the highest level of quality and safety of human source plasma.
*
After consultation with relevant works councils and trade unions, JOHNSON & JOHNSON
announced that it has accepted a binding offer from the CARLYLE GROUP to acquire its
ORTHO-CLINICAL DIAGNOSTICS unit for approximately $4 billion. The transaction
is expected to close near the middle of 2014, upon satisfaction of customary closing conditions.
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*
In an open letter, the chief executive officer of CANADIAN PLASMA RESOURCES
has called for a “Canadian plasma strategy” that takes into account the fundamental
differences between the collection of blood for transfusion and the collection of plasma
for further manufacture into therapeutic plasma protein products. While Canada’s
100% voluntary donation system collects enough blood and other components, including
plasma, to meet the country’s transfusion needs, the “need for plasma products significantly
exceeds our current capacity to produce plasma for further manufacturing,” he noted. The
Ontario province’s Minister of Health has introduced Bill 178, which, if enacted into law,
would prohibit Canadian Plasma Resources from collecting and selling source plasma from
remunerated plasma donors in that province.
“CANADIAN BLOOD SERVICES and Héma-Québec satisfy most of this shortfall by
purchasing plasma protein products from the United States and Europe, and these products
are almost entirely made from plasma collected from paid donors in the United States,” he
pointed out. “We currently import large quantities of plasma products, most of which are
manufactured from plasma from paid donors. For example, more than 70% of immunoglobulinÖis made from paid donor plasma from the United States. We can continue to rely on
purchased plasma protein therapies from the United States and Europe, or we can begin to
develop a made-in-Canada solution.”
While acknowledging that “encouraging greater voluntary donations is important, we must
give serious consideration to providing incentives for repeat, committed plasma donors,” he
said. “These qualified donors commute and donate plasma up to once a week and spend 100
hours annually on plasma donations. Compensation of time and out of pocket expenses can
be consistent with what the province of Ontario is already giving to living organ donors.”
*
BLOOD CENTERS OF AMERICA (BCA) and GSABC COOPERATIVE CORPORATION (GSABC) have announced the merger of the two organizations. Through a friendly
tender offer by BCA to purchase the shares of GSABC from its stockholders, GSABC has
become subsidiary of BCA. The new BCA, comprising non-profit independent blood centers
across the U.S., is now the largest blood supply network in the U.S., with more than 5.4 million blood units collected and distributed annually; this exceeds the 4.9 units collected by the
AMERICAN RED CROSS.
In addition to new operational and cost efficiencies, this merger is expected to enhance members’ ability to:
•
Collect, process, manufacture and handle biologic cells used in cell therapies
•
Expand plasma services and supply capabilities for hospitals and fractionators
•
Enhance client blood management capabilities using state-of-the-art tools and technologies
•
Connect a larger network of reference laboratories across the country.
By combining the memberships, resources and experience of BCA and GSABC, we are now
positioned as a leader in national blood supply in contracting, serving both national and regional healthcare systems and life science organizations,” a senior BCA official said.
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*
Recommendations for optimal hemophilia care in Europe, developed at an April 2013
meeting in Wildbad Kreuth, Germany by experts from 36 EUROPEAN HEMOPHILIA
CONSORTIUM member countries, have been published in the May 2014 issue of Haemophilia. The third initiative of its kind after previous symposiums in 1999 and 2009, the
“Kreuth III” Expert Panel made the following principal conclusions and recommendations:
1: To optimize the organization of hemophilia care nationally, it is recommended that a
formal body be established in each country to include the relevant clinicians, national
hemophilia patient organizations, health ministry, paying authority and (if appropriate)
regulatory authorities.
2: The minimum factor VIII consumption level in a country should be 3 IU/capita.
3: Decisions on whether to adopt a new product should not be based solely on cost.
4: Prophylaxis for children with severe hemophilia is already recognized as the optimum
therapy. Ongoing prophylaxis for individual adults should also be provided when
required based on clinical decision making by the clinician in consultation with the
patient.
5: Children with inhibitors who have failed, or who are not suitable for, immune tolerance therapy (ITI) should be offered prophylaxis with bypassing agents.
6: Single factor concentrates should be used as therapy wherever possible in patients
with rare bleeding disorders.
7: Orphan drug designation for a factor concentrate should not be used to hinder the
development, licensing and marketing of other products for the same condition which
have demonstrably different protein modification or enhancement profiles.
With the goal of ensuring equity of access to immunoglobulin therapies across the European
Union (EU), a separate Immunoglobulin Working Group at the Kreuth III symposium
developed the following recommendations:
1: To adopt a process for management of immunoglobulin demand across the EU in
order to ensure adequate supplies for all patients who need immunoglobulin.
2: For all EU countries to acknowledge that immunoglobulin is a “WHO Essential
Medicine” and to ensure that all patients who need this drug have access to sufficient
quantities of immunoglobulin for this to be clinically effective.
3: That all recognized routes of immunoglobulin administration are made available to
patients.
4: Immunoglobulin products differ from one another.
5: Better mechanisms are required for Health Technology Assessment of immunoglobulin
therapies.
6: More research is needed on the use of immunoglobulin in treatment of secondary
immunodeficiencies.
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*
BIOGEN IDEC disclosed that it will price its new long-acting recombinant factor IX
product, ALPROLIX, to create parity with existing factor IX concentrates on an annual
cost of therapy basis. The Cambridge, Massachusetts biotechnology firm has set the wholesale
acquisition cost (WAC) of ALPROLIX at $2.85 per international unit (IU). While more than
two-fold higher than the $1.19 per IU WAC set for PFIZER’S BeneFIX recombinant factor
IX product, Biogen Idec asserts that the overall cost of treatment – presumptively for routine
prophylaxis – will be similar between ALPROLIX and BeneFIX, after consideration of the
less frequent average dosing required for effective prophylaxis with ALPROLIX.
The recommended starting regimen for routine prophylaxis with ALPROLIX is either 50 IU/kg
once weekly or 100 IU/kg every 10 days, adjusted based on individual response; the overall
median dosing interval with individualized-interval prophylaxis was 12.5 days; during the last
six months of the study the median interval increased to 13.8 days. By contrast, prophylaxis
with BeneFIX requires multiple doses per week. In addition, each IU of BeneFIX administered
per kilogram of body weight increases circulating factor IX activity by only 0.7 to 0.8 IU/dL
on average, with substantial individual variability. This typically necessitates higher doses
of BeneFIX than would be required with use of plasma-based factor IX concentrates.
Biogen Idec reported that it is conducting formal discussions with U.S. health insurance
companies about the pricing of ALPROLIX, including the methodology used to determine its price. “We anticipate that we will get reimbursement and coverage from payers for
ALPROLIX,” a senior company official said.
*
BAXTER INTERNATIONAL announced that it has agreed to acquire CHATHAM
THERAPEUTICS, a development-stage company with programs directed toward the
development and commercialization of treatments for hemophilia. Under terms of the
agreement, Baxter will make an initial payment of $70 million to acquire all of the outstanding
membership interests of the North Carolina-based company. Baxter may make additional payments in the future based on attainment of specified development, regulatory and commercial
milestones.
In mid-2012, Baxter and Chatham entered into a collaboration to evaluate Chatham’s “Biological Nano Particle (BNPTM)” platform -- an advanced recombinant adeno-associated virus
(rAAV)-based gene therapy technology -- as a potential treatment for hemophilia B (see the
June 2012 issue of International Blood/Plasma News). Known as “BAX 335,” this investigational gene therapy is currently being evaluated in a Phase I/II clinical study to assess
its safety and optimal dosing schedule; up to 16 patients are expected to be enrolled.
Baxter also acquires access to Chatham’s preclinical hemophilia A program, as well as the
potential future application of its platform to additional hemophilia targets. Following the
acquisition, Chatham will maintain its licensing and development relationship with Asklepios
BioPharmaceutical (AskBio) relating to the development of novel hemophilia gene therapy
candidates using the “BNPTM” platform.
“Chatham’s gene therapy platform technology offers the potential to redefine treatment of
both hemophilia A and B,” a senior Baxter official said. “This technology will be highly
complementary to our expanding pipeline of bleeding disorder treatments as we continue our
pursuit of a bleed-free world.”
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BLOOD & BIOTECHNOLOGY
*
A week after its approval by Health Canada (see the March 2014 issue of International Blood/
Plasma News), BIOGEN IDEC’S ALPROLIX long-acting recombinant factor IX product
has been approved for marketing by the U.S. FDA. With its U.S. launch expected in early
May, ALPROLIX (Coagulation Factor IX [Recombinant], Fc Fusion Protein) will become the
first DNA-derived hemophilia B therapy featuring prolonged circulating half-life. ALPROLIX is indicated for the control and prevention of bleeding episodes, perioperative (surgical)
management and routine prophylaxis in adults and children with hemophilia B.
The approval of ALPROLIX is based on results from the 50-center, multinational Phase III
“B-LONG” study in 123 males aged 12 years and older with hemophilia B, as well as interim
pharmacokinetic and safety data from the Phase III pediatric “Kids B-LONG” study. These
study results showed that bleeding episodes were prevented or reduced in adults and adolescents with severe hemophilia B with prophylactic infusions administered at least a week apart.
The overall median dosing interval in study patients managed with individualized-interval
prophylaxis exceeded 12 days. Treating physicians rated the ability of APROLIX to control
bleeding as “excellent” or “good” in all 14 major surgical procedures involving 12 study
participants.
Across the routine prophylaxis and on-demand therapy arms, generally minor adverse reactions
were reported in 8.4% of patients; each reported adverse event occurred in two or fewer study
subjects. An interim analysis from the ongoing, multi-center Phase III “Kids B-LONG” study
indicated that no inhibitors were detected. The increase in half-life seen with ALPROLIX in
children was consistent with data reported in adults and adolescents.
*
Separately, BIOGEN IDEC and development partner SWEDISH ORPHAN BIOVITRUM
(SOBI) have released “positive top-line results” indicating that twice-weekly prophylactic dosing with their investigational recombinant factor VIII Fc fusion protein product,
ELOCTATE, maintained low bleeding rates in 71 boys under age 12 years with severe
hemophilia A, and was generally tolerated with no evidence of inhibitor antibodies. In
this “Kids A-LONG” study, the relative increase in half-life in children with severe hemophilia
A was consistent with the 1.5-fold increase in half-life seen in a separate “A-LONG” study
of adults and adolescents.
Children treated prophylactically with ELOCTATE had an overall median annualized bleeding rate (ABR) of 2.0, and a median ABR for spontaneous bleeds of 0.0. Forty-six percent
of participants in the study experienced no bleeding episodes. The average time participants
spent in the study was 25 weeks. Sixty-one children received ELOCTATE infusions on at
least 50 separate exposure days to assess inhibitor development.
“The results of this study support the potential for ELOCTATE to address a signifi-cant need
for children with hemophilia by providing prolonged intervals between scheduled prophylactic
infusions to protect against bleeding episodes,” a senior Bio-gen Idec official said. Assuming
it meets its safety and efficacy endpoints, this study will support applications for pediatric
indications globally.
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*
BAXTER INTERNATIONAL announced top line results from a Phase III clinical trial
evaluating the safety, efficacy and pharmacokinetics of “BAX 111,” the company’s investigational recombinant von Willebrand factor (rVWF) intended for the treatment of
bleeding episodes in patients with von Willebrand disease (VWD). The primary endpoint
was met, with on-demand treatment in all 22 patients who experienced bleeds achieving
bleeding control as pre-specified in the protocol. A total of 37 patients with severe VWD were
administered “BAX 111” together with Baxter’s ADVATE recombinant human factor VIII or
as a stand-alone agent for on-demand treatment of bleeds at trial sites in the U.S., Europe,
Australia, Japan, Russia and India.
There were no reports of inhibitor development or thrombotic events in any study participants.
The most common adverse events were headache, vomiting/nausea and iron deficiency anemia,
which were not considered to be related to treatment. One serious adverse event related to
treatment, characterized by chest discomfort and increased heart rate during infusion; these
symptoms rapidly resolved without further complication.
“BAX 111” is prepared using a plasma-and albumin-free manufacturing method. Both the
European Commission and the U.S. FDA granted orphan drug designation for “BAX 111” in
November 2010. Baxter says it intends to file for marketing approval in the U.S. before the
end of 2014, and based on results of this open-label trial, intends also to organize a study of
“BAX 111” in a prophylaxis treatment setting before the end of 2014.
*
In a “benefit assessment” of NOVO NORDISK’S NovoEight (turoctocog alfa) recombinant factor VIII, Germany’s Institute for Quality and Efficiency in Health Care (IQWiG)
found that the product has no added benefit compared to recombinant factor VIII products already on the market, specifically when compared to octocog alfa products including
ADVATE, Kogenate, Recombinate and Helixate products.
Introduced in 2011, benefit assessments are required for manufacturers to document that
their drug has an additional benefit compared to other marketed products, in order to justify
approval of a higher price. The decision by IQWiG is subject to confirmation by the Joint
Federal Committee (G-BA), which has final authority on all benefit assessments.
*
Cambridge, Massachusetts-based Bluebird Bio has initiated a U.S. Phase I/II Northstar
Study of its autologous hematopoietic stem cell gene therapy, “BB305” or LentiGlobin, for
the treatment of beta-thalassemia major. The first of up to 15 subjects was transplanted last
month. A separate Phase I/II trial of LentiGlobin for beta-thalassemia major is also underway
in France. The disease, which affects about 288,000 persons worldwide and an estimated
15,000 persons in the U.S. and Europe, is caused by a genetic mutation in hemoglobin that
results in dysfunctional red blood cells. Symptoms include anemia and splenomegaly, as well
as iron overload in major organs as a result of frequent blood transfusions.
LentiGlobin treats beta-thalassemia and sickle cell disease by inserting a fully functional betaglobin gene into the patient’s own hematopoietic stem cells, thereby restoring the effective
production of normal hemoglobin. Promising early proof-of-concept findings for one patient
with beta-thalassemia were reported in the 16 September 2010 issue of Nature; that subject
remains transfusion-free more than 60 months post-transplant.
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RESEARCH AND DEVELOPMENT
*
Prescribing treatment to achieve an arbitrary serum albumin level, an open-label trial that
randomized 1,818 Italian patients with severe sepsis or septic shock to receive crystalloids only or crystalloids plus 20% human albumin found no significant difference in
overall 28-day mortality – 32.0% and 31.8%, respectively. At 90 days, there was a small
but non-significant difference in mortality – 41.1% versus 43.6% -- favoring the treatment
arm administered albumin to maintain the serum albumin level at 30 grams per liter or more
for 28 days, or until discharge from the intensive care unit (ICU).
Physicians at 100 ICUs participating in the “Albumin Italian Outcome Sepsis (ALBIOS)”
study were required to dose 20% albumin to reach the 30 gram per liter serum concentration.
On each day the serum albumin level fell below 25 grams per liter in a treatment arm subject,
300 mL of 20% albumin – the oncotic equivalent of 1,200 mL of 5% albumin – was infused.
Through day six, two-thirds of subjects in the albumin arm were still receiving large daily
infusions of 20% albumin, together with substantial volumes of crystalloids.
A post hoc analysis of the subset of 1,121 patients who entered the ALBIOS study in septic
shock determined that those in the albumin treatment group experienced a significantly
lower death rate (43.3% versus 49.9%, P = 0.03; relative risk, 0.87). The study authors
nevertheless concluded that “the findings in our trial may appear to contradict those of the
predefined subgroup analysis from the [2004 Australian/New Zealand] SAFE study, which
suggested a survival advantage [relative risk of 0.87] with a [4%] albumin-based strategy
during severe sepsis.” Their complete report is published in the April 10 issue of The New
England Journal of Medicine.
*
In a presentation last month at the Ninth Congress on Autoimmunity in Nice, French and
U.S. collaborators proposed that “Tregitopes” – natural T regulatory cell epitopes contained in the framework sequences of immunoglobulin G (IgG) – may represent one of
the “active pharmaceutical ingredients” that mediate the tolerance-inducing effects of
polyclonal intravenous immunoglobulin (IVIG) in certain autoimmune disorders, such
as chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). These Tregitopes have previously been identified as an important trigger
for the expansion and activation of regulatory T cells (Tregs).
Defining characteristics of Tregitopes include the following:
•
•
•
They stimulate CD4+, CD25hi and FoxP3+ T cells;
Assays show that they suppress effector T-cell responses to other antigens; and
They are associated with T cell IL-10 production in vivo and in vitro.
The investigators suggest that isolated Tregitope peptides could one day offer an alternative to
IVIG to treat autoimmune disorders for which IVIG has already been demonstrated to exert a
tolerogenic effect. More detailed discussion is published in a review article published online
last December 25 in Clinical and Developmental Immunology.
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*
A team of British investigators has described the use of very low concentrations of a
synthetic, biomimetic polymer to slow the growth of ice crystals and thereby enhance the
cryopreservation of human red blood cells. Only 0.1 wt% of this polymer was required to
attain significant cell recovery post freezing, compared with over 20 wt% required for organic
solvents such as glycerol or dimethyl sulfoxide.
Their results “demonstrate that synthetic antifreeze (glyco)protein mimics could have a crucial
role in modern regenerative medicine to improve the storage and distribution of biological
material for transplantation,” the authors concluded. Complete findings and discussion are
published in the February 3 issue of Nature Communications.
*
OCTAPHARMA has awarded a major research grant to evaluate the long-term effects
of intravenous immunoglobulin (IVIG) maintenance therapy on donor-specific antibodies (DSA) in alloantibody-positive renal transplant recipients. Co-principal investigators
at the Houston Methodist Hospital and the Paul I. Terasaki Foundation Laboratory in Los
Angeles will manage this registry study, in conjunction with DATABEAN, a clinical research
organization that will act as the clinical and data coordinating center.
The study’s aim is to advance our understanding of the pathological processes responsible
for allograft loss and the effects of therapeutic interventions aimed at these pathways. A total
of 162 renal transplant recipients determined to be in need of IVIG therapy will be enrolled
at up to 15 transplant centers in the U.S. and Europe. Change kinetics of Class I and Class
II anti-HLA antibodies in response to IVIG therapy will be monitored for 36 months, and
related to allograft damage as measured by serial renal biopsies. Additionally, New Yorkbased eMAX Health Systems will monitor health care utilization and the economic impact
of disease management for all treated patients.
*
CORD BLOOD REGISTRY has initiated a Phase II clinical trial at the University of
Texas Health Science Center to evaluate the safety and efficacy of delivering autologous
hematopoietic stem cells intravenously to cerebral palsy patients. A total of 30 children
aged two to 10 years will be administered either autologous cord blood stem cells collected
at the time of birth, or autologous bone marrow stem cells collected from a bone marrow
harvest. Five patients from each assigned group will receive a placebo infusion at baseline,
but will be given the option of receiving stem cell treatment after one year. Patient follow-up
examinations will be conducted at six, 12 and 24 months after treatment.
“ Preclinical data indicate that the ongoing neuroinflammatory response is a driver of further
injury in cerebral palsy so the hope is to reduce this neuroinflammation,” the study’s principal
investigator said. The working hypothesis is that infusing a patient‘s own stem cell may trigger mechanisms to alleviate this damage. The study is projected to end in November 2015.
_________________________________________________________________________
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*
KAMADA announced that it has initiated a new Phase II U.S. clinical trial of its proprietary inhaled alpha-1 antitrypsin (AAT) therapy for the treatment of alpha-1 antitrypsin
deficiency (AATD), or hereditary emphysema. This double-blind, placebo-controlled study
will evaluate the safety and efficacy of 80 mg or 160 mg of inhaled human plasma-derived
AAT or placebo delivered via the eFlow device for 12 weeks. All subjects will be able to
enter an additional 12-week open-label extension study with the active drug to further assess
its safety and tolerability.
The study will additionally measure AAT levels in the lung and serum, as well as certain
inflammatory biomarkers in 36 AATD patients. Kamada has completed a Phase II/III
multicenter randomized, double-blind, placebo-controlled study evaluating the safety
and efficacy of its inhaled formulation of human AAT to treat AATD in more than 165
patients in Europe and Canada, and expects to report top-line results by the end of April
or the beginning of May. That study evaluated the inhalation of 160 mg of human AAT or
placebo daily via a dedicated, product-adjusted eFlow device for 50 weeks. Eligible patients
were given the option to participate in a subsequent 50-week open-label extension study
in which all patients receive the active treatment. The primary endpoint of the study is the
difference in exacerbation events between the two groups at one year. Secondary endpoints
include additional parameters of exacerbation events, pulmonary function tests and safety.
“We intend to use data from this U.S. study along with the data from our European Phase II/
III study to support a BLA license filing with the U.S. FDA,” a senior Kamada official said.
“Positive data from the Phase II/III study will also accelerate the variety of strategic options
we are considering in the U.S., including licensing and/or proprietary sales by Kamada,” he
added. Kamada plans to initiate a U.S. Phase II trial of its inhaled AAT to treat cystic
fibrosis in the second half of 2014. The company is also conducting a Phase II/III trial
of its liquid intravenous AAT to treat type 1 diabetes, with interim data expected in
2016, and in cooperation with U.S. licensee BAXTER INTERNATIONAL has initiated
a 24-subject U.S. proof-of-concept trial with its GLASSIA liquid AAT product for the
treatment of graft-versus-host disease (GVHD).
PLASMA FRACTIONATION NOTES
*
GREEN CROSS announced that it plans to build what it says will be the first commercial
plasma fractionation facility in Canada, as part of an initiative to expand its biologics
business to North America. The South Korean biopharmaceutical firm’s new subsidiary,
GREEN CROSS BIOTHERAPEUTICS (GCBT), has secured a financial commitment from
INVESTISSEMENT QUÉBEC for CAD 25 million ($22.7 million) to start construction on
the plant, which will be located in Montréal. Green Cross projects total capital expenditures
in excess of CAD 180 million ($163 million) over the next five years. Construction is set
to begin later this year, according to a company news release, with commercial production
scheduled to start in 2019. The new facility will have the capacity to fractionate up to one
million liters of plasma annually. (continued on page 130)
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With plans to manufacture intravenous immunoglobulin (IVIG), human albumin products and
coagulation factors for the treatment of bleeding disorders, GCBT has also signed an agreement with Héma-Québec to supply IVIG as soon as production begins at the new Canadian
plant. Under this agreement, GCBT will supply IVIG to Héma-Québec for a period of five
years, with renewal options to extend the agreement three years or longer.
“North America is an extremely important market for us. The market for IVIG particularly
is booming with Canada one of the world’s highest per capital users…North America constitutes more than 40% of the global plasma products market,” a senior GCBT official said.
“We expect annual sales will reach up to CAD 300 million over the next 10 years.”
*
GRIFOLS has officially opened its new plasma fractionation plant at Parets del Vallés in
Barcelona, which, once fully operational, will have the capacity to fractionate 2.1 million
liters of plasma per year. Expected to come on-stream shortly, the facility already holds a
European Medicines Agency (EMA) license and Grifols expects to secure an establishment
license from the U.S. FDA before the end of the year.
This new plant doubles Grifols’ plasma fractionation capacity in Spain to 4.2 million liters
per year. Its operation will gradually generate nearly 100 new jobs, including both direct and
indirect employment. Grifols has two fractionation plants in the U.S. – one in Los Angeles,
California with the capacity to fractionate 2.2 million liters and one in Clayton, North Carolina
with the capacity to fractionate more than three million liters – which combine for a fractionation capacity well in excess of five million liters per year. Grifols’ three fractionation plants
can collectively process 9.6 million liters of plasma per year, accounting for approximately
20% of global plasma fractionation capacity.
Grifols reports that it plans to invest more than €600 million ($830 million) between 2014 and
2016 to construct new fractionation, purification and protein filling facilities. These planned
capital expenditures – spearheaded by the construction of a second plasma fraction plant in
Clayton, North Carolina – will increase the company’s total plasma fractionation capacity to
more than 12 million liters by 2016.
PRODUCT SAFETY UPDATE
*
The JAPANESE RED CROSS SOCIETY (JRC) has selected GRIFOLS’ as its partner
to perform nucleic acid screening of approximately 5.3 million Japanese blood donations
each year for HIV and hepatitis viruses. Under terms of the seven-year agreement, Grifols
will provide JRC with its Procleix Panther System and associated assays. The decision to go
with Grifols followed “an extensive in-house evaluation of commercially available systems
against a range of performance criteria, including the efficiency of testing each blood donor
sample separately (called individual donor testing, or IDT) rather than in pools.” (continued
on page 131)
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The JRC will perform IDT using the Procleix Ultrio Elite assay for detection of HIV Types 1
and 2 and hepatitis virus Types B and C in a single multiplex assay. In response to emerging
concerns about hepatitis E virus, the JRC will additionally become the world’s first blood center
to test blood donations in the Hokkaido region with the new Procleix HEV assay. Since its
commercial launch in late 2012, the fully automated Procleix Panther System has been placed
in more than 60 blood screening laboratories worldwide. Grifols’ Procleix line of blood testing assays is developed in partnership with HOLOGIC, formerly GEN-PROBE.
*
CERUS announced that it has submitted a Medical Device license application to Health
Canada for review of its INTERCEPT Blood System for plasma. This follows an agreement reached between the company and Health Canada last November to pursue regulatory
submissions for both INTERCEPT platelets and plasma. A regulatory filing for INTERCEPT
platelets is planned for the second quarter of 2014.
“The parallel regulatory submissions in the U.S. and Canada have enabled us to be efficient
in our filings by leveraging common elements accumulated over ten years in Europe,” a
Cerus official said. Canada’s two blood services, CANADIAN BLOOD SERVICES and
Héma-Québec, supply approximately 70,000 and 55,000 units of plasma for transfusion per
year, respectively.
NEW PRODUCTS
*
The AMERICAN SOCIETY FOR APHERESIS (ASFA) has announced the publication
of Principles of Apheresis Technology, Fifth Edition. This textbook is intended to provide
a basic overview of the theory and applications of apheresis. Topics include:
•
•
•
•
•
•
•
•
•
Basic science and apheresis instrumentation
Therapeutic apheresis procedures
Clinical decision making and ASFA guidelines
Vascular access
Donor apheresis
Apheresis for cellular therapies
Apheresis program management essentials
Regulatory issues and quality activities
Pediatric apheresis: special considerations for children <25 kg
To order, visit the ASFA online store at https://asfamalachite-mgmt.site-ym.com/store/default.
aspx?.
_________________________________________________________________________
Publishers of International Blood/Plasma News© are careful to report accurately from sources believed reliable,
but cannot assume liability for any information published. Errors will be promptly corrected when discovered.
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RECENT U. S. PATENTS
*
Inhibiting Collagen-Induced Platelet Aggregation and Activation With Peptide Variants.
#8,614,188. Assigned to University of Massachusetts (Boston, MA). A method involving
administering a peptide, whose composition is described in the patent, which is capable of
reducing platelet aggregation in a patient having a medical condition resulting from platelet
aggregation.
*
Method of Administration of Platelet-Rich Plasma to Treat an Acute Cardiac Dysfunction. #8,617,539. Allan Mishra (Menlo Park, CA). A method of treating myocardial infarction in an individual comprising introducing an unactivated platelet-rich plasma composition
via catheter or syringe into an area of dysfunctional cardiac muscle using a kit comprising
(i) a syringe for withdrawing blood from a patient; (ii) a centrifuge device to obtain plateletrich plasma; (iii) a pH adjusting agent for the platelet-rich plasma to provide a platelet-rich
composition having a pH of about 7.3 to 7.5; and (iv) a catheter or syringe for delivery of the
platelet-rich plasma composition to dysfunctional cardiac muscle, thereby treating myocardial
infarction.
*
Methods of Preventing or Treating Anthrax Using Anti-Anthrax Antibodies. #8,617,548.
Assigned to Elusys Therapeutics, Inc. (Pine Brook, NJ). A method of preventing the development of inhalation anthrax in a human subject that has been exposed to B. anthracis spores,
the method comprising administering intramuscularly a composition comprising an antibody
which neutralizes B. anthracis toxin to the subject and further comprising administering at
least one antibiotic to the subject, wherein the antibody light chain variable region set forth as
amino acid residues 1-107 in SEQ ID NO:2 and the heavy chain variable region amino acid
sequence set forth as amino acid residues 1-119 in SEQ ID NO:1.
*
Sequence Diversity Generation in Immunoglobulins. #8,617,845. Assigned to Innovative
Targeting Solutions, Inc. (Vancouver, Canada). An isolated host cell that is capable of in
vitro immunoglobulin gene rearrangement and which comprises a first nucleic acid composition for generating immunoglobulin structural diversity comprising a tripartite recombination
substrate characterized in the patent.
Composition, Method, and Kit for Preparing Plasmin. #8,617,863. Assigned to Grifols
Therapeutics, Inc. (Research Triangle Park, NC). A method for preparing plasmin, the method
comprising (a) contracting a plasminogen composition with a streptokinase immobilized on a
matrix thereby converting the plasminogen to a plasmin, wherein the streptokinase is a mutant
capable of activating plasminogen to plasmin, yet resistant to plasmin degradation relative to
its corresponding wild-type streptokinase; and wherein the streptokinase comprises an amino
acid sequence having an amino acid residue other than lysine at a position corresponding to
position 85, 412, or both positions; and (b) purifying the plasmin by a method comprising
contacting the composition with a plasmin-binding matrix so that the plasmin is retained by
the plasmin-binding matrix.
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*
Methods for Producing Recombinant Proteins. #8,617,881. Assigned to Excelimmune,
Inc. (Woburn, MA). A method for producing a polyclonal cell population, said method comprising the steps of (a) transforming one or more host cells with at least one vector comprising
at least one copy of a nucleic acid sequence that encodes a component of a polyclonal protein
composition, in the presence of recombinase or integrase, such that the at least one vector
integrates into the host cell genome at a plurality of locations recognized by the recombinase
or integrase; (b) generating a cell population, without clonal selection, capable of producing
the component of the polyclonal protein composition; and (c) mixing the cell population and a
different cell population producing a different component of the polyclonal protein generated
by performing steps (a) and (b), each cell population comprising greater than about 10,000
individual cells to produce a polyclonal cell population capable of producing the polyclonal
protein composition.
*
Cultured Hematopoietic Stem Cells and Method for Expansion and Analysis Thereof.
#8,617,885. Assigned to Whitehead Institute for Biomedical Research (Cambridge, MA).
A method for expanding hematopoietic stem cells (HSCs) ex vivo, comprising culturing a
population of cells that include hematopoietic stem cells in a medium comprising insulin-like
growth factor 2 (IFG-2) and stem cell factor (SCF), under conditions sufficient for expansion
of HSCs, thereby both expanding HSCs ex vivo and enriching for HSCs relative to the initial
population of cells.
*
Thrombopoietic Compounds. #8,618,044. Assigned to Amgen, Inc. (Thousand Oaks, CA).
A method of increasing megakaryocytes or platelets in a patient in need thereof, comprising
administering an effective amount of a compound comprising SEQ ID NO:34 [or SEQ ID
NO:46].
*
Methods and Compositions for Treating Conditions Related to Lack of Blood Supply,
Shock and Neuronal Injuries. #8,618,056. Cuthbert O. Simpkins (Shreveport, LA). A
method for raising blood pressure in a subject, comprising infusing an effective amount of a
pharmaceutical composition comprising (i) a lipid component, (ii) an amphiphilic emulsifier
and (iii) a polar liquid carrier, wherein the lipid component and the amphiphilic emulsifier
form free-moving lipid-carrying micelles in the polar liquid carrier, wherein the pharmaceutical composition is free of hemoglobin and fluorocarbon, and wherein said composition is
infused in an amount that equals to, or is greater than, 10% of the normal blood volume of
said subject.
*
Modified Human Plasma Polypeptide or Fc Scaffolds and Their Uses. #8,618,257. Assigned to Ambrx, Inc. (La Jolla, CA). A human serum albumin (HSA) comprising a nonnaturally encoded amino acid at one of the following positions: 34, 172, 301, 364, and 505 of
SEQ ID NO:1, which are linked to one or more biologically active molecules selected from the
group consisting of inhibin peptides, interleukin proteins, and interleukin receptor proteins.
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*
Freeze-Dried Fibrin Matrices and Methods for Preparation Thereof. #8,618,258. Assigned
to Prochon Biotech Ltd. (Nessa Ziona, Israel). A method of treating diseased or injured tissue, comprising implanting into the tissue at a site of disease or injury a porous freeze-dried
fibrin matrix formed from plasma proteins comprising factor XIII and fibrinogen cleaved by
thrombin, wherein the matrix has less than 10% residual moisture and is devoid of exogenous
anti-fibrinolytic agents, plasminogen and organic chelating agents, and wherein the diseased
or injured tissue is selected from the group consisting of cartilage, bone, liver, pancreas, and
cardiac tissue.
*
Polymer-Factor VIII Conjugate Compositions. #8,618,259. Assigned to Nektar Therapeutics (San Francisco, CA). A composition that is at least 85% free from albumin, the
composition comprising a conjugate comprising a water-soluble polymer covalently attached
to a factor VIII polypeptide via a thiol group of a cysteine residue that has been added to or
substituted in the factor VIII polypeptide, wherein the water-soluble polymer is selected from
a group specified in the patent.
*
Stabilized Liquid and Lyophilized ADAMTS13 Formulations. #8,623,352. Assigned to
Baxter International, Inc. (Deerfield, IL) and Baxter Healthcare SA (Glattpark, Switzerland).
A stabilized aqueous formulation of ADAMTS13 for lyophilization, comprising (a) 0.05 mg/
dL to 10.0 mg/mL ADAMTS13; (b) 0 mM to 100 mM of a pharmaceutically acceptable salt;
(c) 0.5 mM to 20 mM calcium; (d) 2% to 6% of a sugar and/or sugar alcohol; (e) a nonionic
surfactant; (f) a buffering agent; and (g) a pH between 6.0 and 8.0.
*
Method for Testing Treatment of ADAMTS13 Deficiency. #8,623,612. Assigned to Baxter
International, Inc. (Deerfield, IL) and Baxter Healthcare SA (Glattpark, Switzerland). A
method for testing effectiveness of a treatment for increasing a disintegrin and metalloproteinase
with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity or concentration in
a subject, comprising measuring a level of von Willebrand factor (VWF) cleavage fragments
in a blood sample from the subject before and after the treatment, wherein an increase in
VWF cleavage fragments or a decrease in the amount of ultra-large multimers forms of VWF
with a reduced triplet structure after the treatment indicates that the treatment is effective in
increasing ADAMTS13 activity or concentration in the subject.
*
Composition for Plasma and Serum Separation, and Container for Blood Testing.
#8,623,655. Assigned to Sekisui Medical Co., Ltd. (Tokyo, Japan). A serum or plasma
separating composition containing a liquid resin component having a partition wall-forming
capability; a hydrophilic inorganic powder; a hydrophobic inorganic powder; and an organic
compound serving as a thixotropy enhancer, wherein the organic compound is a polyalkylene
glycol and/or derivative thereof.
*
Sickle Confirm Modified Hemoglobin Solubility Test. #8,623,659. Assigned to Saint Louis
University (St. Louis, MO). A method for determining sickle-cell zygosity.
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MEETINGS
June 12-15, 2014
19th Congress of the European Hematology Association
MiCo - Milano Congressi
Milan, Italy
Phone: +31 70 3020 099
Email: info@ehaweb.org
Web: www.ehaweb.org
September 9-12, 2014
Annual Meeting of the German Society for
Transfusion Medicine and Immuno-Hematology (DGTI)
Dresden, Germany
Phone: +49 3641 311 60
Email: martin.singer@conventus.de
Website: www.dgti-kongress.de
June 26-27, 2014
PPTA Plasma Protein Forum
J.W. Marriott
Washington, D.C.
Phone: 202-789-3100
Email: info@pptaglobal.org
Website: www.pptaglobal.org
September 18-20, 2014
66th Annual Meeting
National Hemophilia Foundation
Washington, DC
Phone: 212 328-3700
Email: handi@emophilia. org
Website: www.hemophlia.org
July 1, 2014
The Great World Fluid Debate
Institute of Education, London
Phone: +44 20 7612 6000
Email: events.reg@expotel.com
Website: www.ebpom.org/greatFluidDebate2014-Venue
September 23-24, 2014
IPFA/BCA inaugural Global Symposium
on the Future for Blood and Plasma Donations
Sheraton Grand
Sacramento, CA
Phone: +31 20 512 356
Email: info@ipfa.nl
Website: www.ipfa.nl
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