MONITORING INTERNATIONAL
TRENDS
posted November 2012
The NBA monitors international developments that may influence the management of blood
and blood products in Australia. Our focus is on:
 Potential new product developments and applications; and
 Global regulatory and blood practice trends; and
 Events that may have an impact on global supply, demand and pricing, such as changes
in company structure, capacity, organisation and ownership; and
 Other emerging risks that could potentially put financial or other pressures on the
Australian sector.
A selection of recent matters of interest appears below. Amongst the highlights:
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A range of new clotting factors are in development.
An overseas economic model suggests that when hospital costs are taken into account,
higher dosing of subcutaneous immunoglobulin therapy in patients with primary
immunodeficiencies is cost-effective compared with intravenous immunoglobulin.
Two drugs which were thought to offer some hope for Alzheimer’s patients –
bapineuzumab and solanezumab- did not meet their endpoints in clinical trials, although
there is some suggestion they may have some positive effect early in the disease. The
spotlight is focussed now on the trial of Baxter’s intravenous immunoglobulin in
Alzheimer’s disease, due to report in 2013.
A product made from human blood past its use- by date is claimed to boost the capacity
of red cells to deliver oxygen to organs and tissues after trauma- induced bleeding.
Blood salvage technology designed at the University of Strathclyde, Glasgow, has
gained both European and Canadian approval.
Table of Contents
Products................................................................................................................................ 1
Regulatory matters ................................................................................................................ 3
Market structure and company news ..................................................................................... 4
Overseas events ................................................................................................................... 6
Safety ................................................................................................................................... 7
Research .............................................................................................................................. 8
Legal actions and enquiries, Infectious Diseases………………………………………
11
Products
Here the NBA follows the progress in research and clinical trials that may within a
reasonable timeframe make new products available, or may lead to new uses or changes in
use for existing products.
Clotting factors.
a) Biogen Idec and Sobi also announced positive results from their Phase III study
of their long- lasting rFVIII fusion protein in haemophilia A. They said their ALONG study showed their rFVIIIFc was effective in controlling and preventing
1
bleeding, in routine prophylaxis, and in peri-operative management. A Biologic
License Application (BLA) will be submitted to the FDA in the first half of 2013.
The European Medicines Agency (EMA) requires a study in children less than 12
years of age prior to filing, so a Marketing Authorization Application cannot be
submitted to the EMA until completion of the Kids A-LONG study.
b) Novo Nordisk in October announced the submission of the application for
marketing authorisation for turoctocog alfa (NN7008) to the FDA and EMA.
Turoctocog alfa is a third-generation rFVIII for prevention/ treatment of bleeding
in haemophilia A. The application is based on the results from clinical trials
Guardian1 and Guardian3, completed in 2011. More than 200 patients round the
world were enrolled, making Guardian the largest clinical pre-registration trial
programme conducted in haemophilia A. The phase III trials included previously
treated adults and children with severe haemophilia A and demonstrated efficacy
in preventing and treating bleeds with no development of inhibitors. Applications
for regulatory approval in other countries will follow. Novo Nordisk’s rFXIII
(NN1841) has already been submitted for approval, and the company has a longacting rFIX derivative in development.
c) Prolor Biotech’s FVIIa differs from NovoNordisk’s experimental FVIIa therapy,
vatreptacog alfa, on which work was recently discontinued. In the NovoNordisk
compound, three amino acids had been substituted to enhance platelet enzyme
activity, but this has not been done in the Prolor drug which uses Carboxyl
Terminal Peptide technology (CTP) to extend half- life.
Immunoglobilin
d) At the 15th Biennial Meeting of the European Society for Immunodeficiencies,
Elie Haddad (Professor, Department of Pediatrics, Microbiology and Immunology,
University of Montreal) presented a new economic model to demonstrate that
higher dosing of subcutaneous immunoglobulin therapy (SCIg) is cost-effective in
patients with primary immunodeficiencies compared with intravenous
immunoglobulin (IVIg). The higher doses of SCIg are cheaper than IVIg therapy
because they mean lower costs for hospital care. The speaker said: “This new
model shows that, in addition to the benefits of improved clinical outcomes and
increased patient satisfaction, SCIg also provides true monetary value across a
wide range of dosing scenarios.”
e) In children with acute Kawasaki disease, a randomized, double-blind, placebocontrolled trial showed that adding Remicade (infliximab, a tumor necrosis factor
inhibitor) to standard treatment with IVIg plus aspirin did not affect treatment
resistance or coronary artery outcomes1.
f) Grifols announced in September that it had a robust inventory of rabies immune
globulin (human) to overcome US supply constraints. The product immediately
protects people exposed to rabies who have not been vaccinated. They are then
given a series of rabies vaccinations to ensure permanent immunity.
Patient Blood Management
g) Sandoz, the generic arm of Novartis, has marketed biosimilar epoetin alfa2 in the
European Union for five years under the brand name Binocrit, but is now
conducting a Phase III trial in the US.
h) The American Society of Nephrology’s Kidney Week 2012 meeting began on
October 30 in San Diego3. FibroGen presented data on FG-4592- its oral
1
Tremoulet, et al "Phase III randomized, double-blind, placebo-controlled trial of infliximab for
intensification of primary therapy for Kawasaki disease" IDWeek 2012.
2 a biosimilar version of Epogen and Procrit, made by Amgen and Johnson & Johnson, and used for
anaemia in chronic kidney disease.
2
i)
hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) clinical candidate
for the treatment of anaemia in chronic kidney disease. Medgenics presented on
its Epodure Biopumps4.
Sangart’s MP4OX is made from human blood stocks past their use-by date. It is
claimed to carry no infection risk and be safe for all patients after a traumatic
bleeding event. It is not a substitute for transfusion of red cells, but is said to
increase the ability of red cells to do their job, delivering an oxygen boost to
organs and tissues. It is currently in a Phase IIb trial in 56 locations round the
world.
Other
Adventrix Pharmaceuticals is initiating a Phase III clinical study of ANX-188, or
purified poloxamer 188, in sickle cell disease at around 40 sites in the US. The
primary objective will be to show that ANX-188 reduces the duration of vasoocclusive crisis in patients with sickle cell disease.
k) HemoSonics has partnered with Cambridge Consultants to complete
development of its point-of-care analyzer to to test the four treatable systems that
control clotting: platelets, coagulation factors, fibrinogen and fibrinolytic proteins.
l) The Pharming Group has completed a Phase III trial of Ruconest (recombinant
human C1 inhibitor) to treat acute attacks in hereditary angioedema.
j)
Regulatory Matters
The NBA monitors overseas regulatory decisions on products, processes or procedures
which are or may be of relevance to its responsibilities.
a) Terumo BCT's Mirasol(R) Pathogen Reduction Technology System has been
authorized for use in Austria The first customer, Europlasma GmbH, which
supplies hospitals in the Vienna region, will use the Mirasol System for platelets.
b) Terumo BCT has been cleared by the FDA to prepare plasma held at 1° to 6° C
within 8 hours and frozen within 24 hours after phlebotomy, and plasma held at
room temperature for up to 24 hours and frozen within 24 hours after phlebotomy,
from apheresis plasma collected on the company’s Trima Accel Automated Blood
Collection System. These extended handling permissions facilitate the use of
satellite collection centres and mobile blood drives. Fenwal has received FDA
clearance for plasma products collected on the Fenwal Alyx® and Amicus®
systems to be held up to 24 hours before freezing. These systems are already
cleared to collect fresh frozen plasma, which is frozen within eight hours.
c) Kamada has FDA approval for a Phase II/ III clinical trial of the inhalable version
of its treatment of Alpha-1 antitrypsin deficiency, to manage congenital
emphysema. Kamada hopes that if its Phase II/III clinical trial currently underway
in Europe is successful, this may suffice. Data will be available late in 2013.
d) Duke University’s School of Medicine has FDA approval to sell Ducord, a stem
cell product derived from cord blood, for use in transplants between unrelated
donors and patients whose diseases or treatments damage bone marrow cells.
3
View online at www.asn-online.org/education/kidneyweek/archives/. The oral and poster
presentations were respectively:FG-4592, an Oral Hypoxia-Inducible Factor Prolyl Hydroxylase
Inhibitor, Corrects Anemia Without Iron Supplementation in Incident Dialysis Patients (Besarab, et al),
and FG-4592, a Novel Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor (HIF-PHI), Maintains
Hemoglobin Levels and Lowers Cholesterol in Hemodialysis (HD) Patients: Phase 2 Comparison with
Epoetin Alfa (Provenzano, et al).
4
The poster, titled “Novel Sustained Delivery of Erythropoietin in Hemodialysis Patients for Safer
Anemia Control using EPODURE™ Biopumps – Autologous Dermal Tissue Samples Secreting
Erythropoietin,” presents preliminary data from a Phase IIa clinical trial of EPODURE to treat anemia
patients with end stage renal disease (ESRD).
3
e) Thomson Reuters reported the “orphan drug” market is worth over $US50 billion
annually: “The high cost of therapy and attractive developmental drivers, such as
government incentives (including tax credits), smaller and shorter clinical trials,
extended exclusivity and high rates of regulatory success, have made top orphan
drugs as equally viable as their non-orphan peers.” Of the 86 drugs considered,
25 generated sales in excess of $US1 billion. Some were approved for use in
more than one rare illness.
f) The FDA’s Blood Products Advisory Committee discussed bacterial
contamination of platelets5, and Hepatitis E in relation to transfusion safety6. The
FDA provided final guidance on pre- storage leukocyte reduction of whole blood
and blood components intended for transfusion7. The FDA’s Center for Biologics
Evaluation and Research (CBER), in response to the recent severe storm on the
US east coast, issued guidance on the Impact of Severe Weather Conditions on
Biological Products8. Repeated appeals for blood donors and platelet donors
were issued by blood banks after the storm.
g) The EMA has started an infringement procedure against Roche Registration Ltd9.
The European Commission requested an investigation of allegations that the
company has failed to comply with pharmacovigilance obligations in relation to its
19 centrally authorised medicines. Starting this procedure means that the Agency
will further investigate within the legal framework of Regulation (EC) No
658/2007. It does not prejudge the outcome of the investigation.
Market Structure and Company News
The NBA’s business intelligence follows company profitability, business forecasts, capital
raisings or returns, mergers and takeovers, arrangements for joint research and/or
development, contracts for supply of manufacturing inputs, and marketing agreements.
Companies of interest include suppliers, potential suppliers and developers of products
which may be of interest.
a) At CSL’s annual meeting, the Chairman said growing healthcare systems in
emerging markets would also provide growth for CSL. The company already has
20 per cent of the Chinese market for albumin. The company is to improve its
capital strength and earnings per share by buying back another $A900 million in
shares before November 2013. It initiated a similar buyback a year ago.
5
September 20-21, 2012: Blood Products Advisory Committee Meeting: FDA Issue Summary:
"Considerations for Strategies to Further Reduce the Risk of Bacterial Contamination in Platelets"
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVacc
inesandOtherBiologics/BloodProductsAdvisoryCommittee/UCM319539.pdf
6
FDA Blood Products Advisory Committee Meeting: "Hepatitis E Virus (HEV) and Blood Transfusion
Safety Sept 2012
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVacc
inesandOtherBiologics/BloodProductsAdvisoryCommittee/UCM319542.pdf?source=govdeliv
ery
7
FDA Final Guidance for Industry: Pre-Storage Leukocyte Reduction of Whole Blood and Blood
Components Intended for Transfusion.
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Gui
dances/Blood/ucm320636.htm
8
It said: While people should not be put at risk by using a product that may be unsafe due to the
conditions under which it was stored, shortages should not be created by discarding product simply
because of power failures that may not adversely affect the product. Its guidance covered vaccines
requiring refrigeration or frozen storage, other non-blood biologicals requiring refrigeration or frozen
storage and blood products and plasma derivatives.
9
This comes three months after the EMA found that Roche failed to report tens of thousands of
adverse events in connection with its various drugs, including 15,161 patient deaths.
4
b) In its five-year, long-range financial outlook Baxter International is looking for
compound annual sales increases of 5%. Baxter’s profits have increased for
more than a year on strong demand from haemophilia and immunodeficiency
markets. Its $US1 billion investment in new plant will alleviate capacity constraint
in plasma therapies, although if the trial of Gammagard in Alzheimer’s Disease
gives positive results10 severe pressure can still be expected in the IVIg market.
The company’s new plant in Georgia is expected to be operational by 2018.
Baxter has also taken a financial interest in development of a recombinant
version of IVIg.
c) Gliknik researchers have generated GL-2045, a recombinant Fc fusion protein
designed to mimic the efficacy and safety of IVIg in patients with autoimmune
diseases. Clinical studies are scheduled to begin in late 2013. In October Gliknik
announced that it raised $US 4.9 million in Series B Financing. Baxter Ventures,
an initiative created in 2011 by Baxter International, led the Series B raising, and
was joined by existing investors.
d) On October 31 Grifols announced that its nine- month net profit had increased
fourfold over the same period last year.
e) Novo Nordisk increased operating profit by 34 per cent in the first nine months
of 2012. The company was the leading Danish contributor to US election
funding, but the Copenhagen Post reported that the company has been criticised
for backing opponents of President Obama’s healthcare reform, since its own
ethical standards say it is “firmly committed to improving access to health”.
f) Swedish Orphan Biovitrum announced a third-quarter 2012 loss of 45.4 million
Swedish Krona, compared with last year's 38.4 million Swedish Krona loss.
Quarterly total revenues went up 4 per cent to 463.8 million Swedish Krona, from
447.1 million Swedish Krona in the prior-year quarter.
g) In Heidelberg Octapharma opened a €25 million research facility dedicated to
recombinant protein drug development.
h) France’s Ipsen and Massachusetts company Inspiration Biopharmaceuticals
in August renegotiated their strategic partnership agreement for the development
and commercialization of Inspiration’s recombinant product portfolio: OBI-1, a
recombinant porcine factor VIII (rpFVIII) for the treatment of patients with
acquired haemophilia A and congenital haemophilia A with inhibitors, and
IB1001, a rFIX for the treatment and prevention of bleeding in patients with
haemophilia B. Ipsen made an upfront payment to Inspiration and gained
commercial rights in key territories. Inspiration remained responsible for the
world-wide development of OBI-1 and IB1001 and could receive further
investment from Ipsen. Ipsen then controlled 40 per cent of Inspiration and held
$US 200 million in convertible bonds. However, in July the FDA had placed a
clinical hold on a trial of IB1OO1 after patients developed antibodies to the
Chinese hamster ovary protein in it; and it was not long before Ipsen faced a
$US153 million write-off when Inspiration filed for Chapter 11 bankruptcy
protection and prepared for asset sales.
i) Italian plasma products producer Kedrion bought Grigols’ factory in Melville, NY.
It is to receive a subsidy of $US3.3 million from New York State for preserving
and creating jobs. It has also arranged tax breaks with Suffolk County.
j) Cangene Corporation reported financial results for the year to 31 July. Net loss
was $C28.3 million compared with net income of $C1.5 million the year before.
This included $C32.8 million less in revenue on its US government deliveries.
k) Haemonetics delayed completing its acquisition of Hemerus Medical, when the
FDA delayed approval of a Hemerus product, the SOLX whole blood collection
10
The results of the trial in 360 patients in the US and Canada will be known first. Another Phase III
trial in 400 patients from a wider range of countries will start in 2013.
5
system The acquisition is contingent on the FDA approval. The FDA requested
additional information from Hemerus. Approval is now expected by mid-2013.
l) Irish company Elan announced in August it would spin off its Neotope drug
discovery business platform as a separate public company. This makes Elan
immediately profitable despite the failure in trials of its experimental Alzheimer's
drug bapineuzumab developed with Pfizer and Johnson & Johnson.
m) The Board of NuSep resolved in mid- October, subject to shareholder approval,
to spin out its therapeutic plasma fractionation business, called PrIME Biologics.
PrIME Biologics intends to open up the Asian therapeutic plasma market
particularly by tapping into the market for currently unprocessable plasma (CUP).
Over the last six months PrIME has signed a Heads of Agreement to supply CUP
products to India and completed the purchase of a cGMP1 facility in Singapore.
It is drawing down a Singapore Government loan and installing the pilot scale
PrIME production unit into the Singapore facility.
n) Merck and AiCuris have entered into an exclusive worldwide licensing
agreement for AiCuris' portfolio of investigational medicines directed at human
cytomegalovirus, including letermovir (AIC246), an oral, late-stage antiviral being
developed to treat/ prevent infection in transplant recipients.
o) Pharmacyclics has made an agreement with Novo Nordisk under which the
latter will acquire the world-wide rights to PCI-27483 for specific non-cancerrelated uses11. The Danish company plans to use it as an excipient, usually an
inactive ingredient used to carry or to add a certain consistency to a drug.
Overseas Events
The NBA is interested in relevant safety issues which arise in particular countries, and also
instances of good practice. We monitor health issues in countries from which Australia’s
visitors and immigrants come.
United States
a) By 5 November 2012, thirty people are known to have died and 419 have
become ill from an outbreak of fungal meningitis linked to contaminated steroid
injections from a compounding pharmacy.
b) The possible need for donor screening for babesiosis continues to be a matter for
discussion, along with ways this might be achieved12.
c) In the US, the Securities and Exchange Commission is reported to have asked
Pfizer to explain why its pre- tax earnings in 2011 were $US15 billion outside the
US, while within the US it made a loss of $US2.2 billion. Forty per cent of its
sales are generated outside the US.
d) Research released at the American Public Health Association's 140th Annual
Meeting in San Francisco, demonstrated that the variation in size of red blood
cells known as "red cell distribution width," (RDW) most recently used as a
predictor of hospitalization outcomes and mortality, is linked to socioeconomic
factors, with higher RDW found at lower socio- economic levels- and also among
African Americans.
11
Pharmacyclics has been developing PCI-27483 to prevent blood clots in cancer patients and to
inhibit the intracellular signaling involved in tumor growth.
12
Cushing M, Shaz B. “Transfusion-transmitted babesiosis: achieving successful mitigation while
balancing cost and donor loss”. Transfusion 2012;52: 1404-7. Bloch EM, et al, “The third described
case of transfusion-transmitted Babesia duncani”. Transfusion 2012;52: 1517-22. Young C, et al,
“Preventing transfusion-transmitted babesiosis: preliminary experience of the first laboratory-based
blood donor screening program”. Transfusion 2012;52: 1523-9. Johnson ST, et al, “Lookback
investigations of Babesia microti-seropositive blood donors: seven-year experience in a Babesiaendemic area”. Transfusion 2012;52: 1509-16.
6
e) A study of 464 hospitals by Premier13 suggested they could save over 800,000
units of blood annually (reducing their costs by $US165 million) if they followed
the practices of the top 25 per cent of hospitals. Recommendations included
following evidence- based transfusion guidelines, establishing multidisciplinary
blood stewardship teams, and developing processes to monitor adherence to
guidelines and provide feedback to clinicians
Other
a) A recent study14 in the Netherlands examined the impact of donor psychology on
b)
c)
d)
e)
f)
blood donation, along with the influence of needle reactions on the risk of donors
not returning. Vasovagal or needle reactions are reflexes of the involuntary
nervous system characterized by arteriolar dilation. They may lead to nausea,
vomiting, weakness, hypotension, bradycardia, or syncope. The study showed
female donors were more likely to have vasovagal reactions than males, although
male donors were more likely to cease donating after a reaction. Dr. Wim de
Kort, the Director of Donor Services at Sanquin Blood Bank in the Netherlands,
was the senior author of the study. He is also the project leader of the European
Union funded DOMAINE project evaluating donor management.
The Bahrain Society for Sickle Cell Anaemia Patient Care plans legal action
against the Health Ministry, after the 33rd sickle cell patient death for the year.
In Pakistan, research at the National Institute of Blood Diseases found that in
aplastic anemia was 5.8 times more common in the country than in the Western
countries. It identified possible links with the use of painkillers or exposure to
pesticides and benzene.
The Korea Times reported that over 100 people had been transfused with blood
infected with Hepatitis B. This was discovered by the Red Cross when it
introduced a new testing method and retested blood previously offered for
transfusion.
In Hong Kong, four women who were re- transfused with their own blood at a
beauty clinic became ill with septic shock, and one died. Contamination with the
bacteria mycobacterium abscessus was suggested as the cause.
In Indonesia, Sanofi Pasteur and the Eijkman Institute for Molecular Biology will
operate a joint dengue research laboratory. Sanofi Pasteur will provide the
Eijkman Institute with additional research equipment and train the Eijkman’s
researchers.
Safety Issues
We follow current issues in patient safety.
a) Reviews of James Reynolds' documentary, Primum Non Nocere: First Do No
Harm, say it makes a strong case for the ill effects of blood transfusions.
b) A randomized clinical trial involving several Canadian hospitals15 suggests that
severely ill premature babies transfused with fresh blood do no better than those
transfused with blood stored for a week16.
c) Leanne Clifford, of the Mayo Clinic in Rochester, Minnesota, reported to a
meeting of the American Society of Anesthesiologists 17 that in a single- centre
13
In the fall 2012 edition of their Economic Outlook
Veldhuizen I, Atsma F, van Dongen A, de Kort W. “Adverse reactions, psychological factors, and
their effect on donor retention in men and women”. Transfusion 2012. Masser BM. “Experienced
donors, adverse events, and retention”. Transfusion 2012.
15
The Age of Red Cells in Premature Infants (ARIPI) trial involved 377 babies of less than 1250 gms
16
Dean Fergusson et al, Journal of the American Medical Association, October 8 2012.
14
7
retrospective study the rates of transfusion complications and other morbidities
was similar in patients who received red blood cells less than 8 days old and
those who received blood more than two weeks old. This included length of
hospital stays and time in ICU.
d) At a 2012 AABB conference18, the transfusion medicine community discussed
risks from bacterial contamination of platelets and the possible costs and benefits
of secondary bacterial screening tests along with their efficacy. Speakers
suggested investigating further point-of-issue testing to reduce residual risk. The
2012 meeting also included a session on therapeutic plasma exchange in
paediatric patients.
e) Before the AABB annual meeting a two- day Physicians’ Workshop was devoted
to patient care and outcome strategies viewed from several perspectives. Topics
included the rationale for patient blood management, haemovilance and
transfusion safety, red blood cell transfusion guidelines, plasma use in clinical
practice, platelet transfusions, interventions during cardiopulmonary bypass,
point-of –care coagulation testing, pre- operative anaemia management, and
coagulation management19.
f) A systematic review20 evaluated quality guidelines for red blood cells (RBC)
exposure to uncontrolled temperatures. The current standard considered was
that RBCs should be transfused within 4 hours of leaving controlled temperature
storage; and RBCs should not be returned for re-issue if they were outside a
controlled temperature environment for more than 30 minutes. The review
suggests both standards may be extended, although further research is needed.
Variability in temperature and exposure duration in the studies considered restrict
the interpretations of this review.
g) Haemochromatosis, an inherited blood disorder characterized by iron overload, is
treated with regular therapeutic phlebotomy. People in the US with hereditary
haemochromatosis have been able to donate blood since 2001, but many
European countries do not permit this. Researchers from the Belgian Red Cross
systematically reviewed six observational studies on the safety and efficacy of
donation from haemochromatosis patients, and recommended that donations
from patients without complications be regarded as acceptable for transfusion21.
Research
A wide range of scientific research has some potential to affect the use of blood and blood
products. However, research projects have time horizons which vary from “useful tomorrow”
17
Clifford L, et al "Transfusion of aged red blood cells has no impact on the outcomes of critically ill
patients" ASA Meeting 2012; Abstract LBC04.
18
Public Conference –“ Secondary Bacterial Screening of Platelet Components.” Meetings and
Events. AABB. Web. 23 Aug. 2012. <http://www.aabb.org/events/conference/Pages/conf.aspx>
19
http://www.aabb.org/events/annualmeeting/attendees/65amonline/Pages/saturday_patientca
re1.aspx
http://www.aabb.org/events/annualmeeting/attendees/65amonline/Pages/saturday_patientca
re2.aspx
20
Brunskill S, Thomas S, Whitmore E, McDonald CP, Doree C, Hopewell S, Staves J, Cardigan R,
Murphy MF. What is the maximum time that a unit of red blood cells can be safely left out of controlled
temperature storage? Transfus Med Rev 2012;26: 209-23 e3.
21
Two of the six found that the blood from hemochromatosis patients was more susceptible to
bacterial growth, but the researchers suggested this should not be the case where patients had
normalized iron levels. De Buck E, et al. “Is blood of uncomplicated hemochromatosis patients safe
and effective for blood transfusion? A systematic review”. J Hepatol. 2012 May 30.
8
to “at least ten years away”. Likelihood of success of particular projects varies, and even
research which achieves its desired scientific outcomes may not lead to scaled- up
production, clinical trials, regulatory approval and market development.
a) Two scientists have been awarded the Nobel Prize in medicine for the discovery
that cells in the body can be reprogrammed into completely different kinds of
cells. British researcher John Gurdon and Japanese scientist Shinya Yamanaka
showed how to make the equivalent of embryonic stem cells without the ethical
questions that attach to them. This offered a promise which scientists are now
trying to realize to deal with a wide range of medical conditions. However,
Yamanaka has warned patients about unproven "stem cell therapies" offered at
clinics and hospitals in a growing number of countries. He said "This type of
practice is an enormous problem, it is a threat. Many so-called stem cell
therapies are being conducted without any data using animals, preclinical safety
checks." Yamanaka, who calls the master stem cells he created "induced
pluripotent stem cells" (iPS), hopes to see the first clinical trials soon.
b) In a small trial at Johns Hopkins University, researchers have found they can help
sickle cell patients who cannot find matches to receive bone marrow from donors
who are only half-matches.
c) An evaluation22 of the pros and cons of harvesting stem cells from bone marrow
instead of blood– for patients whose bone marrow has been destroyed- found
that there are benefits to both approaches, but no patient survival differences
between the two choices.
d) At the International Society of Blood Transfusion Congress, researchers from the
Bristol Institute for Transfusion Services outlined progress in producing laboratory
cultured human red blood cells (RBCs)23. RBCs derived from adult peripheral
CD34+ cells had earlier been demonstrated to be viable in the peripheral
circulation of a volunteer patient. These cells were probably predominantly latestage reticulocytes. Study of the cultured cells using confocal microscopy
indicated the way these reticulocytes develop into erythrocytes. Results support
the view that it may be possible to produce cultured therapeutic RBCs. The
challenge of scale-up to produce sufficient quantities remains, as does ensuring
an affordable price. The expectation is that this would be through using human
induced pluripotent stem cells.
e) Australia’s Strategic Review into Health and Medical Research24 reported a need
to integrate research and health services. Its draft recommendations included
investing at least 3 per cent of federal and state health expenditure on research
activity within the health system; creating “Integrated Health Research Centres”
combining hospital networks, universities and medical research institutes; and
establishing practitioner fellowships for clinicians to fund 50 per cent of their time
to ensure research is embedded in patient care.
f) A website to facilitate patient recruitment to clinical trials in Australia was
launched In October by the federal Minister for Health and the Minister for
Innovation and Industry. Improving patient recruitment was one of the
recommendations of the Clinical Trials Action Group, a panel set up to look at
ways of arresting the decline in clinical trial activity in Australia. There is also a
link to a “Find a clinical trial” website, with details of trial registries (e.g., the
Australian New Zealand Clinical Trials Registry, ClinicalTrials.gov), clinical trial
22
Claudio Anasetti, M.D., professor, medicine, University of South Florida, and senior member, H.
Lee Moffitt Cancer Center and Research Institute, Tampa, Fla.; Frederick Appelbaum, M.D., director,
clinical research, Fred Hutchinson Cancer Research Center, Seattle; Oct. 18, 2012, New England
Journal of Medicine
23
Anstee DJ. “Production and characterization of cultured human red cells”. ISBT Science Series:
International Congress of the International Society of Blood Transfusion, 2012:102-3.
24
9
www.mckeonreview.org.au
g)
h)
i)
j)
k)
l)
m)
n)
25
organisations, research networks, co-ordinating hubs and support groups. See
www.australianclinicaltrails.gov.au
Patients undergoing caesarean sections at the Royal Cornwall Hospital are
offered cell salvage, where lost blood is returned after cleaning. New research is
examining whether cell salvage can be used in normal births, outside sterile
theatres. Funding has been provided by The National Institute of Academic
Anaesthesia.
Researchers from the University of Utah told the International Society of Blood
Transfusion Congress that platelet development and proliferation continue even
after platelets have entered the bloodstream, and may persist under steady-state
culture conditions25. This is contrary to earlier understanding that platelet
development ends as soon as megakaryocytes generate platelets through
proplatelet formation. The findings may have significant implications for platelet
storage and transfusion.
A meeting of the American Society of Anesthesiologists was told that patients
given high doses of a steroid during coronary artery bypass surgery were less
likely to need transfusions of blood products26.
Scientists at the Sloan-Kettering Institute for Cancer Research in New York have
been able to make a fully synthetic version of erythropoietin27. Previously EPO
has had to be produced in cell cultures.
An Australian study has demonstrated that “in children and adolescents with
haemophilia, vigorous physical activity is transiently associated with a moderate
relative increase in risk of bleeding”.28
New research suggests that the A, B and O blood types in humans evolved at
least 20 million years ago in a common ancestor of humans and other primates29.
Research at the University of Pennsylvania30 found that clots forming in arterialflow conditions can sense blood movement. If flow ceases, the clot initiates a
muscle- like contraction and squeezes out water. Appreciating the different
clotting dynamics in atherosclerosis and in wound closure may lead to drugs
which are more effective in preventing heart attacks.
Anaemia associated with sickle cell disease has been attributed to abnormally
shaped sickle cell red blood cells blocking capillaries. Now scientists from Drexel
University and St. Christopher’s Hospital for Children in Philadelphia suggest31
that it is a difference in the shape and structure of haemoglobin in the red blood
cells of sickle cell patients that causes blood vessel occlusion.
Schwertz H, Rowley JW, Tolley ND, Campbell RA, Weyrich AS. “Assessing protein synthesis by
platelets”. Methods Mol Biol 2012;788: 141-53.
Schwertz H, Weyrich AS. Generation of platelet progeny. ISBT Science Series: International
Congress of the International Society of Blood Transfusion, 2012:104-5.
26
Dieleman JM, et al "The effect of high-dose dexamethasone on transfusion of blood products in
cardiac surgical patients" ASA 2012; Abstract LBC10. This result is from a post hoc study of a
randomized controlled trial, to be reported in the Journal of the American Medical Association.
27
Danishefsky, S. At Last: Erythropoietin as a Single Glycoform. Angewandte Chemie International
Edition. dx.doi.org/10.1002/anie.201206090
28 Carolyn R. Broderick,Robert D. Herbert, Jane Latimer, Chris Barnes, Julie A. Curtin, Erin Mathieu,
Paul Monagle, and Simon A. Brown: Association Between Physical Activity and Risk of Bleeding in
Children With Hemophilia” JAMA. 2012;308(14):1452-1459. doi:10.1001/jama.2012.12727.
29
L. Ségurel et al. "The ABO blood group is a trans-species polymorphism in primates." Proceedings
of the National Academy of Sciences. doi:10.1073/pnas.1210603109
30
published in the journal Arteriosclerosis, Thrombosis and Vascular Biology, of the American Heart
Association.
31
Aprelev et al.: "The Physical Foundation of Vaso-occlusion in Sickle Cell Disease." Biophysical
Journal , October 17, 2012
10
o) Results have been reported32 from the Stroke With Transfusions Changing to
Hydroxyurea (SWiTCH) randomized trial in sickle cell patients. Of 67 patients
treated with hydroxyurea and phlebotomy to manage liver iron content, 7 had
strokes. Of 66 patients treated with transfusion and deferasirox iron chelation,
none had strokes. Liver iron content was not reduced more by the phlebotomy
than by chelation. Negative results caused early termination of the trial.
p) A team at Washington University in St Louis, examining families with a genetic
risk of Alzheimer’s Disease, concluded from blood and spinal fluid tests, brain
checks and tests of cognitive skills that signs of how Alzheimer’s progresses
were evident 25 years in advance. Meanwhile, at the Mayo Clinic and the Basel
Mobility Centre in Switzerland, researchers found that changes in a person’s gait
were an early predictor of cognitive decline.
Legal issues
a) Scotland’s Penrose inquiry -into how patients became infected in the 1970s and
1980s with hepatitis and HIV from blood products supplied by the NHS- has been
told by solicitors representing some of the patients that it should hear evidence
from more witnesses. The Inquiry has already been running four years and is
expected to report next year.
b) Ireland’s High Court ordered that a Jehovah’s Witness could be transfused with
non- red blood products despite her husband’s objections. The judge accepted
she had told doctors the previous day that she would receive plasma or platelets.
Infectious diseases
The NBA takes an interest in infectious diseases because: the presence of disease in
individual donors (e.g. influenza), or potential disease resulting from travel (e.g. malaria)
means a donor must be deferred; temporary disease burden within a community (e.g.
dengue in North Queensland) may limit blood collection in the community for a time; and
some people may not be permitted to donate at all (e.g. people who lived in the UK for a
period critical in the history of vCJD). Blood donations are tested for a number of diseases
(e.g. HIV and Hepatitis B), but there are also emerging infectious diseases for which it may
become necessary to test in the future (e.g. Chagas disease, and the tick-borne babesiosis
and Lyme disease).
Mosquito- borne diseases
a) Western Australia has experienced significant outbreaks of Ross River virus in
2012.
b) Papua New Guinea has had its first known outbreak of chikungunya. Singapore
has had a record number of chikungunya cases this year. Researchers from
Yong Loo Lin School of Medicine in National University of Singapore (NUS)
"successfully identified a genetic sequence - called 'small hairpin RNA' for the
shape of the sequence - which stops the chikungunya virus from replicating
before going on to destroy the virus", the Straits Times reported.
Sexually Transmitted Diseases
a) Australian HIV infection rates increased by more than 8 per cent in 2011
Professor John de Wit, director of the National Centre in HIV Social Research,
said the increase is in large part due to unsafe sex among gay men, who he says
32
Ware RE, Helms RW.” Stroke With Transfusions Changing to Hydroxyurea (SWiTCH)”. Blood
2012;119: 3925-32.
11
see HIV/AIDS as no longer life threatening. The Australian Federation of AIDS
Organisations wants rapid HIV testing licensed for use in Australia.
b) The Canadian Supreme Court in October announced new appeals judgments
that will continue to allow the criminalisation of non-disclosure of HIV status. HIV
and AIDS advocates condemned the judgments.
c) The number of gonorrhoea cases in Australia rose 21 per cent in 2011, but
chlamydia is still the most common sexually-transmitted infection, with more than
80,000 cases reported. A spike in syphilis in Halifax, Nova Scotia, has been
mostly attributed to sexual liaisons arranged through the internet, and similar
reasons have been identified for a substantial increase in syphilis in young gay
and bisexual men in Christchurch, New Zealand.
c) A report in the Archives of Internal Medicine says antiretroviral therapy helped
lead to a sharp decline in the number of Americans dying from HIV/AIDS-related
causes between 1993 and 2007. Rates remained the same for the leasteducated black women: reasons for this included poor access to care and hence
the length of time before starting treatment.
Other
a) There has been concern about tuberculosis in Australia’s north. A homeless
Aboriginal man who had travelled widely round Queensland was diagnosed in
Mossman with a highly infectious strain of potentially lethal tuberculosis. He is
known to have infected five people with whom he had been in close contact, and
all GPs in far north Queensland were contacted and advised to look out for
symptoms of the disease in high- risk patients.
b) A new disease has produced AIDS- like symptoms in people in Asia and some in
the US, but they are not infected with HIV. Their immune systems are
compromised and they cannot fight infection. The disease does not appear to be
contagious33.
c) A vaccine against Hendra virus in horses is now commercially available in
Australia, and its use should assist in preventing human deaths.
33
New England Journal of Medicine, Aug 22, 2012.
12