Feds, states split $25M in settlement

WASHINGTON (Legal Newsline) - The U.S. Justice Department announced on Friday that a Danish pharmaceutical manufacturer will pay $25 million to resolve its civil liability arising from the allegedly illegal promotion of its hemostasis management drug.
The Food and Drug Administration approved Novo Nordisk's hemostasis management drug NovoSeven to treat certain bleeding disorders in hemophiliacs. After FDA approval, a manufacturer may not market or promote a drug for uses not specified in its new drug application or for uses not approved by the FDA. Unapproved uses are known as "off-label" uses.
Novo Nordisk's U.S. subsidiary, which is located in Princeton, N.J., allegedly promoted NovoSeven to healthcare professionals for off-label uses, including as a coagulatory agent for trauma patients, general surgery, cardiac surgery, liver surgery, liver transplants and intra-cerebral hemorrhage.
False claims were submitted to government healthcare programs that were not reimbursable because of Novo Nordisk's unlawful promotion, it was alleged. The federal share of the civil settlement is $21,425,790.59. The state Medicaid share of the civil settlement is $3,574,209.41.
"Health care patients should be able to trust that their prescription drugs are safe, effective and prescribed only for FDA approved uses," Maine Attorney General William Schneider said. "These off-label promotions waste Maine taxpayer dollars and we will seek recovery from pharmaceutical companies for this kind of healthcare fraud."
The settlement resolves a a whistleblower lawsuit filed under the qui tam or whistleblower provisions of the False Claims Act that is pending in the District of Maryland. Under terms of the resolution, the whistleblowers are set to receive more than $3.5 million from the federal share of the civil recovery.
Novo Nordisk also agreed to enter into an expansive corporate integrity agreement with the Office of the Inspector General of the Department of Health and Human Services as part of the settlement. That agreement creates procedures and reviews meant to avoid and promptly detect similar conduct in the future.

Novo Nordisk presents positive clinical data on two investigational compounds within bleeding disorders

New data presented at American Society of Hematology annual meeting highlight promising treatments that may help patients with bleeding disorders to better manage their condition than today.
Orlando, US – (7 December 2010) – Novo Nordisk presented data from a phase 2 trial evaluating the safety, pharmacokinetics and efficacy of a recombinant factor VIIa (rFVIIa) analogue, designed to have a faster action profile than NovoSeven® (rFVIIa) in haemophilia patients with inhibitors (antibody formation against factor preparations). The company also presented data from a phase 3 trial investigating a recombinant compound in patients with congenital factor XIII deficiency, a rare, inherited bleeding disorder. The data were presented at the 52nd American Society of Hematology (ASH) Annual Meeting and Exposition.
rFVIIa analogue (NN1731)[1]: phase 2 results
Results were presented from a phase 2 trial, adept™1, in which haemophilia patients aged 12 years or older experiencing a joint bleed were randomised to  receive up to three doses of NN1731 or NovoSeven®. The trial showed that NN1731 was safe and no antibody formation against NN1731 was seen in the trial. Evaluation of patients who received NN1731at the two highest dose levels showed that 96% of the joint bleeds were well-controlled with the product; the efficacy of NovoSeven® was similar to that observed in previous clinical studies (efficacy in approximately 90% of bleeds).
In addition, the number of adverse events (AEs), including serious adverse events (SAEs), was lower in patients being treated with NN1731 compared to those in the control group. A total of 12 SAEs were reported and all occurred 16 days or longer after exposure to NN1731.
“There were no safety concerns observed in patients at any dose level of NN1731,” said Dr Erich de Paula, of the State University of Campinas in São Paulo, Brazil, who presented the trial during the meeting. “Additionally, the phase 2 trial results demonstrated the potential of the rFVIIa analogue to stop joint bleeds quickly and effectively. These results further support the distinct fast action profile of the rFVIIa analogue in treating bleeds in haemophilia patients with inhibitors.”
NovoSeven® was used as a control in the trial due to its proven efficacy and safety profile. NovoSeven®was specifically developed to treat people with haemophilia A or B with inhibitors to factor VIII or IX replacement.
rFXIII compound: phase 3 results
Results were presented from mentor™1[2], a phase 3 trial examining the efficacy and safety of a recombinant factor XIII (rFXIII) compound for the prevention of bleeds associated with congenital FXIII deficiency, a rare bleeding disorder with about 600–1,000 diagnosed patients worldwide.
In the trial, 41 patients were treated for one year, with rFXIII administered as a preventative, once-monthly replacement therapy for congenital FXIII deficiency. FXIII-deficient patients with no previous history of FXIII treatment were used as a control. Currently, the only treatment available is derived from human blood plasma, which carries an inherent risk of infections.[3]
The trial results demonstrated that treatment with monthly recombinant FXIII injections significantly decreased the number of bleeding episodes requiring treatment compared to the historic control group. Over the course of the treatment period, a total of five bleeding episodes were observed in four patients. All five events were associated with trauma, and were not related to low FXIII activity levels in patients. Additionally, no thromboembolic events or fatal adverse events were reported.
“These data show the potential for rFXIII to become a safe and effective treatment option for patients who would otherwise use treatments at risk for contamination,” said Prof Aida Inbal of the Hemostasis Unit and Hematology Clinic in the Institute of Hematology at Rabin Medical Center in Tel Aviv, Israel. “We think this is an extremely important milestone in the development of a treatment that is not sourced from human plasma for patients suffering from congenital FXIII deficiency.”
Novo Nordisk plans to file for US Food and Drug Administration approval of the rFXIII in the first half of 2011.

Blood-clotting drug given to wounded soldiers can cause heart attacks

A drug given to wounded soldiers in Iraq and Afghanistan may be putting their lives in further danger by causing heart attacks and strokes.
The treatment is used to stop serious bleeding in injured troops, but trials show the drug increases the risk of blood clots forming in arteries, which can kill or cause complications that result in amputation.
The dangerous side effects are all the more concerning because years of trials have yet to prove the drug is any better at saving the lives of injured soldiers than a placebo.
The drug, called NovoSeven, was licensed more than a decade ago to stop bleeding in haemophiliacs, but is used by military doctors and in civilian hospitals on an "off-label" basis to treat patients suffering from major blood loss due to trauma or surgery. The drug, also known as recombinant factor seven, costs several thousand pounds per patient but an effective alternative called tranexamic acid costs just £5 per patient.
A spokesman for the Ministry of Defence confirmed that NovoSeven was used by UK forces as "a medicine of last resort", when all other attempts to stem bleeding had failed. The US military also uses the drug.
Prof Ian Roberts, an expert in trauma care at the London School of Hygiene and Tropical Medicine, warned in 2006 that NovoSeven was being used off-label before trials had clarified whether or not it helped save lives.
"There are both civilian patients and wounded soldiers who will have been given this drug and the best evidence shows they would not have benefited, but would have experienced heart attacks, strokes and possible amputations," Roberts said.
By continuing to use the drug, the military and hospital surgeons were leaving themselves vulnerable to legal action, he added. "You cannot defend giving this treatment outside of a randomised controlled trial," he said.
He added that the US military, which has used NovoSeven for years, should explain why it embraced the drug. "What advice were they acting on? Was the advice they received truly independent, or were people compromised in any way? It is important to know," he said.
Dr Mads Krogsgaard Thomsen, chief science officer at Novo Nordisk, the Danish company that makes NovoSeven, said the drug posed very low risk when used under licence to stop bleeding in haemophiliacs and for certain rare blood clotting disorders. "We cannot encourage as a company, by any means, the off-label use of NovoSeven. This is not something we are promoting and it is not something we are responsible for."
Thomsen estimates that between 10% and 20% of NovoSeven is used off-label. "Every now and then, physicians do use it as a last resort in patients that are otherwise likely to die," he said.
Roberts believes the case for using NovoSeven is weakened further by the availability of a much cheaper alternative drug, tranexamic acid, which is known to save lives in bleeding patients without dangerous side effects. A trial of tranexamic acid, called Crash-2, was published in the Lancet in June.
Marcel Levi, professor of internal medicine at Amsterdam Medical Centre, published a review of NovoSeven trials in the New England Journal of Medicine last week that was funded by NovoNordisk. "If you look at whether the drug stops bleeding, or whether fewer transfusions are needed, then many studies are positive. If the only thing that matters is mortality, then it is much harder to prove that this is a useful drug," he said.
Beverley Hunt, a consultant haematologist who worked on the Crash 2 trial at Guy's and St Thomas's Hospital in London, said: "The issue around the use of factor seven in patients with massive blood loss is that there is a lack of evidence to show us how clinically efficacious it really is, what dose to use and when to use it. The problem with using an agent that alters blood clotting is that it is a tightrope walk in reducing the risk of bleeding without increasing the risk of blood clots.
"The recent data showing that its use is associated with a 5% risk of arterial thrombosis means we should not be using it early in the management of massive blood loss. If however despite normal good practice, somebody is bleeding to death and you have nothing left, are you willing to take a 5% risk of arterial thrombosis, and the answer is yes you are."

FDA APPROVES 8 MG VIAL OF NOVOSEVEN®

Novo Nordisk announced today that the U.S. Food and Drug Administration (FDA) has approved NovoSeven® RT (Coagulation Factor VIIa [Recombinant] Room Temperature Stable) in an 8 mg vial size, making the hemophilia A or B with inhibitors treatment available in 1, 2, 5 and 8 mg vials. The 8 mg vial allows a rapid initiation and administration of this medication for those patients who need a larger dose. In addition, FDA has also approved the extension of shelf life for all vial sizes from 24 months to 36 months at room temperature (at or below 77 degrees Fahrenheit).

NovoSeven® RT is specially formulated to treat people with hemophilia A or B with inhibitors. Hemophilia, which is typically diagnosed in childhood, is a chronic, inherited bleeding disorder that occurs when certain blood clotting factors are missing or do not work properly, resulting in easy bruising and prolonged bleeding from trauma. Spontaneous internal bleeding can occur as well, particularly in the joints and muscles. Inhibitors, a serious complication that can occur after treatment, develop in as many as 30 percent of those with hemophilia. In these cases, antibodies form that neutralize or attack the blood coagulation agents contained in the treatment, resulting in joint disease and making it more difficult to manage bleeds.

"When I get a bleed, I want to infuse my treatment right away. The faster I treat a bleed, the sooner I can continue with my daily routine," said Bob Hoyt, a member of the Novo Nordisk Changing Possibilities Coalition. "Using fewer vials will be a positive change for patients." Hoyt has been living with hemophilia with inhibitors most of his life.

For many people living with hemophilia with inhibitors, the 8 mg vial will allow for faster reconstitution - the time it takes to prepare the injection - than their current NovoSeven® RT regimen. Those who previously had to use three vials to deliver an 8 mg dose will now have to reconstitute only one vial. Though the amount of powder in the 8 mg vial is larger than the 5 mg vial, the vial will be the same size and will have a yellow cap to distinguish it from the smaller dose.

"We have heard from patients and physicians alike that when they are treating a bleed, every second counts. We at Novo Nordisk are committed to improving the lives of people living with hemophilia with inhibitors," said Eddie Williams, Vice President, Biopharmaceuticals, at Novo Nordisk. "The NovoSeven® RT 8 mg vial will allow patients to get the medicine they need much faster when experiencing a bleed, without having to manage multiple vials. We're also pleased that it will have a positive environmental impact as well - fewer vials may mean less waste."

The new vial size is expected to be available by November.

Special Challenges of Hemophilia Patients and Their Families

PRINCETON, N.J., Aug. 27 /PRNewswire-FirstCall/ -- More than 160 families of patients living with a rare form of hemophilia are coming together at educational summits sponsored this fall by the National Hemophilia Foundation (NHF) and the Center for Biomedical Continuing Education (CBCE). For the fifth year, the Inhibitor Education Summits will connect patients and their families with expert healthcare professionals and fellow patients to address pertinent topics such as effective pain management, exercise and nutrition, financial security, and psychological wellbeing. The summits are supported by an educational grant from Novo Nordisk.

Hemophilia is a chronic, inherited bleeding disorder that occurs because certain blood clotting factors are missing or do not work properly. Spontaneous internal bleeding can occur, especially in the joints and muscles.

The 2009 summits will take place in Hollywood, C.A., August 27-30 and in Washington, D.C., September 17-20. These summits are the first and only events of their kind that focus specifically on patients with inhibitors. Inhibitors are rare, affecting approximately 800 to 900 Americans. Inhibitors are a serious complication that can develop after treatment in as many as 30 percent of people with hemophilia, most commonly in young children. These patients develop antibodies (or inhibitors) that circulate in the blood stream and actually neutralize, or attack clotting replacements, resulting in an increased risk of bleeding, arthropathy (or joint disease), physical disability and death.

People living with this disease often navigate tremendous challenges, both physically and emotionally. Sid Ramirez, age 21, has lived with hemophilia his entire life. He developed inhibitors at the age of three. His condition led to significant problems with his knee joints, leaving Sid wheelchair bound by age 11. He underwent lateral knee replacement surgery as a teenager, which enabled him to walk again.

"The summits allow others living with inhibitors and their families to learn from each other's experiences and from experts. No one can understand what you go through as well as those who have experienced it themselves and their families," said Sid. "Hemophilia has significance in the decisions I make, but I will not let it be the deciding factor." Currently enrolled in culinary school to pursue his lifelong passion for cooking, Sid is excited about the future ahead.

NHF Chief Executive Officer Val Bias has a special reason for participating in the summits. He's also a person with hemophilia.

"Education has been a cornerstone of the NHF, and the Inhibitor Education Summit is a prime example of that," said Bias, who will also speak at both summits. "We believe it is critical to be able to provide these kinds of programs that help patients and their families achieve greater success in managing inhibitors."

In addition to education for patients and caregivers, there is a comprehensive Youth Camp for children with inhibitors and their siblings. Children attending the Youth Camp will have the opportunity to show their parents all that they have learned during their time at "camp." There is also ample time for networking with other families and "ask the experts" sessions to interact with physicians and other key opinion leaders in the field. Since the Inhibitor Education Summits began in 2005, hundreds of families have benefited from this unique opportunity to learn and connect with others who share their experience.

"Comprehensive management of hemophilia with inhibitors is vital for maximizing the quality of daily life for patients with this difficult condition," said Dr. Guy Young, Director, Hemostasis and Thrombosis Center, Childrens Hospital Los Angeles and co-chair of the summits. "The 2009 Inhibitor Education Summits provide patients and their families with the opportunity to learn effective management strategies, connect with expert medical professionals, and share experiences with other families." Dr. Leonard Valentino, Director, RUSH Hemophilia and Thrombophilia Center, RUSH University Medical Center, is also co-chair of the summits.

For more information about The Inhibitor Education Summits, log onto www.inhibitorsummits.org.

About the National Hemophilia Foundation (NHF)

The National Hemophilia Foundation is dedicated to finding better treatments and cures for bleeding and clotting disorders and to preventing the complications of these disorders through education, advocacy and research. Established in 1948, the National Hemophilia Foundation has chapters throughout the country. Its programs and initiatives are made possible through the generosity of individuals, corporations and foundations as well as through a cooperative agreement with the Centers for Disease Control and Prevention (CDC).

About CBCE(TM) (The Center for Biomedical Continuing Education)

The CBCE(TM) is a full-service provider of accredited CME/CE with a circular scope of capabilities. Since 1999, the CBCE has partnered with clinical experts in solid tumors and hematologic malignancies to develop and implement local, regional, national and international medical education initiatives designed to accelerate the adoption of best practices and clinical breakthroughs in oncology. The CBCE is dedicated to creating rigorous educational programs at the forefront of science, customized according to the target audience. Our unique experience in oncology and hematology has resulted in an in-depth understanding of the nuanced working lives and learning styles of the specialists, nurses, and pharmacists involved in cancer care, an understanding that informs the development of all interventions.

The CBCE vision is to encourage healthcare professionals to commit to change and to define distinct outcomes in their practices that will improve patient care and quality of life.

About Novo Nordisk

Novo Nordisk is a healthcare company with an 86-year history of innovation and achievement in diabetes care. The company has the broadest diabetes product portfolio in the industry, including the most advanced products within the area of insulin delivery systems. In addition to diabetes care, Novo Nordisk has a leading position within areas such as hemostasis management, growth hormone therapy, and hormone therapy for women. Novo Nordisk's business is driven by the Triple Bottom Line: a commitment to economic success, environmental soundness, and social responsibility to employees and customers. With headquarters in Denmark, Novo Nordisk employs more than 27,000 employees in 81 countries, and markets its products in 179 countries. Novo Nordisk's B shares are listed on the stock exchanges in Copenhagen and London. Its ADRs are listed on the New York Stock Exchange under the symbol 'NVO'. For global information, visit novonordisk.com; for United States information, visit www.novonordisk-us.com.

Novo stops NovoSeven trauma Phase III trial

COPENHAGEN, June 11 (Reuters) - Denmark's Novo Nordisk (NOVOb.CO: Quote, Profile, Research) said on Wednesday it stopped a Phase III trial with its NovoSeven drug for treatment of bleeding in severe trauma, but added the decision was not due to safety concerns.
It said the study population had a mortality rate of 10 percent compared to more than 25 percent in the preceding Phase II trial. The study, it said, was unlikely to determine whether NovoSeven would be successful in this treatment area.
"Of course it's not positive but I had not factored in an additional (indication) for NovoSeven," said Sydbank analyst Rune Dahl. "The way to view NovoSeven currently is as (a drug with) stable sales in its existing area, and nothing more." NovoSeven is a haemophilia drug with total sales of 5.9 billion Danish crowns ($1.23 billion) last year.
By 1302 GMT, Novo shares were down 1 percent at 310 crowns on the Copenhagen exchange after briefly falling as much as 4 percent.
A Novo Nordisk spokesman said that the company had not yet decided whether to design a new Phase III study with NovoSeven for bleeding in severe trauma.
In February 2007, Novo Nordisk halted regulatory filing for the drug for bleeding in the brain after initial results from a Phase III clinical trial showed NovoSeven reduces bleeding in the brain but does not improve long-term clinical outcomes.

Novo Nordisk and Neose Announce Completion of Initial Phase 1 Clinical Trial

COPENHAGEN, Denmark & HORSHAM, Pa.--(BUSINESS WIRE)--Novo Nordisk A/S (NYSE:NVO) and Neose Technologies, Inc. (Nasdaq GM:NTEC) today announced that Novo Nordisk has completed the initial Phase 1 clinical trial with NN7128 (GlycoPEGylated Factor VIIa), a long-acting version of NovoSeven® Coagulation Factor FVIIa (Recombinant) administered intravenously. The trial assessed the safety and pharmacokinetics of NN7128 in 30 healthy subjects.
In the trial a significant prolongation of the half-life of NN7128 was observed. Furthermore, single doses of NN7128 were well tolerated with no serious adverse events.
“We are pleased to report the successful completion of this Phase 1 study and to have demonstrated a prolonged half-life of NN7128,” said Søren Bjørn, Corporate Vice President, Biopharm Research at Novo Nordisk. “As we continue our analysis of the data collected in this study, we look forward to presenting the full results at upcoming scientific and medical meetings.”
“We are encouraged by the safety and pharmacokinetic profile that NN7128 has demonstrated in this Phase 1 study,” said George J. Vergis, Ph.D., Neose President and Chief Executive Officer. “We look forward to continued progress in the clinical development of this compound.”

FDA Approves New Formulation of Coagulation Therapy

WASHINGTON (Reuters) - Denmark's Novo Nordisk won U.S. approval to sell a new formulation of a genetically engineered protein therapy that helps the blood clot, regulators said on Friday.
The product, NovoSeven RT, can be stored at room temperature for up to two years, the Food and Drug Administration said. An older formulation had to be refrigerated.
NovoSeven RT is a genetically engineered version of Factor VIIa, a protein found in plasma that is essential for the clotting of blood.
Approved uses of NovoSeven RT include treatment of bleeding, and prevention of surgical bleeding, in certain patients with hemophilia.

Read FDA News HERE

Novoseven

Novo Nordisk has the following interesting details plus another video.


Blood use
- Some statistics
Approximately 10,000 units of blood are required per day to meet the demands of hospitals in England and North Wales. Thirty-two thousand units of red blood cells are used per day in the USA and 26.5 million units of blood are transfused per year. Similar requirements exist throughout Europe.
To meet these demands, 2.5 million blood donations are made in the UK every year, and almost 14 million in the USA. At each donation, approximately 475 ml (1 unit) of blood are collected. 1.9 million volunteer donors in the UK and 8 million in the USA (approximately 5% of the population of each country) donate this blood. With 10% of the adult population (260,000) donating blood Denmark has the highest participation rate as well as the highest consumption of blood products per capita in Europe and is primarily due to the high acceptance of blood donation in Denmark.
Donation by apheresis is also becoming increasingly common and essential for the supply of specific components. Apheresis describes any procedure in which blood is drawn from a donor and a component (platelets, plasma or white blood cells) is separated out, with the remaining blood being returned to the body. Apheresis allows the donor's blood volume to replenish itself much more quickly than whole blood donation. One type of apheresis, plasmapheresis, is commonly used in commercial blood banks. In plasmapheresis the plasma is separated from donated blood, the red blood cells being returned to the donor.
How many components can be made from one unit of blood?
Once blood has been tested for infectious agents and blood groups have been determined, it is separated into its useful components, allowing several patients to benefit from one unit of whole blood.
Red cells are used for the treatment of certain types of anaemia, such as bone marrow failure, sickle cell disease and anaemia associated with chronic renal failure. Transfusion is also used to replace lost red cells after accidents, surgery and childbirth. Red cells have a shelf life of up to 42 days, but if fresh-frozen can be stored for up to 10 years.
Platelets are mainly used in the treatment of patients with bone marrow failure or those undergoing chemotherapy. The shelf life of platelets is up to five days.
Fresh frozen plasma (FFP) is normally used after substantial blood loss, for example following childbirth or during cardiac surgery. FFP is also used for the reversal of anticoagulant treatments, burn/shock cases and to replace clotting factors after blood transfusion. Its shelf life is one year.
Processed plasma is also fractionated for the production of factor VIII and factor IX, immunoglobulins and antibodies. Very large 'pools' of donated units of plasma are used in the production of such products.
The main uses of whole blood are: general surgery (23%), general medicine (15%), cardiothoracic surgery (13%), orthopaedics (11%), haematology (9%), accident and emergency (8%).
Expense associated with blood collection
Collecting blood is expensive. The main costs are for staff salaries, transport, storage, and for the screening tests required by individual nations in addition to blood aquisition cost. In Europe, blood is usually screened for:
Type (ABO/Rh)
Antibodies to red cell antigens
Antibodies to HIV-1/2 and HIV antigen
Antibody to HTLV I/II
Hepatitis B surface antigen and antibody to the core antigen
Antibody to hepatitis C
Syphilis
Liver function (alanine aminotransferase)
Blood transfusion
The majority of blood transfusions are heterologous (also referred to as allogenic), which means that the patient receives donated blood from another person (usually an unnamed volunteer donor via a blood bank or transfusion service such as 'The National Blood Service' in the UK or the 'American Association of Blood Banks' (AABB).
Alternatively patients can donate and later, that is during elective surgery, receive back their own blood (autologous transfusion). Autologous blood donors can give blood twice weekly for up to five weeks prior to elective surgery. After donating, the patient is immediately given IV fluids to compensate for the decrease in blood volume. The advantage of this type of donation is that disease transmission and allergic reactions are eliminated - the patient's own blood is the safest blood for their transfusion needs. Autologous transfusion is also useful for patients with rare blood types who might have difficulty in finding a compatible donor. In addition, autologously collected blood can be frozen and stored for up to 10 years. Disadvantages of autologous transfusions include the fact that the donation must be planned in advance, that it may delay surgery, and that certain medical conditions (eg cardiac conditions under which patients cannot tolerate sudden blood loss) disqualify individuals from this type of donation. Units infected with HBV or HIV from autologous donations, are not stored in the blood bank because of the potential risk of clerical error.
Blood that would otherwise be lost during surgery can also be collected and returned to the patient. This is a different kind of autologous donation called perioperative autologous transfusion or PAT and reduces the need for allogenic blood transfusion. Anticoagulant is added to this salvaged blood prior to centrifugation and washing of the resulting packed red cells. These are pumped into a transfusion bag and re-infused into the patient during or after some types of surgery, such as cardiac, gynaecologic and orthopaedic procedures.
Autologous transfusions are generally more costly than traditional heterologous transfusions and are only appropriate in certain types of treatment. Patients must be stable enough to donate their own blood and to cope with the potential anaemia that may be suffered after surgery.

Human Coagulation factor VII in Fish

A human blood-clotting factor used to treat some people with haemophilia and accident victims suffering serious bleeding has been produced using genetically modified fish.
There is still a long way to go before any product reaches the market, but if the fish project is a commercial success many other proteins might be made in this way.
"We have a list of 20 other human therapeutic proteins that could be produced via fish to treat lung disease, liver problems, even tumours," says Norman Maclean of the University of Southampton in the UK.
Maclean has been working on producing human coagulation factor VII in fish together with AquaGene of Alachua, Florida. Factor VII can be purified directly from human blood, but there is a risk of diseases being transmitted this way.
The only alternative, called NovoSeven, is produced using genetically modified hamster cells. But growing mammalian cells is very expensive, and the cost of a single injection can be as high as $10,000.
Gunshot wounds
Factor VII is used to treat people with a rare form of haemophilia that means they cannot make the protein themselves, and it is often needed to treat other forms of the disease as well.
Many doctors, including US army medical staff in Iraq, are now also using it to stem internal bleeding caused by accidents or gunshot wounds, even though NovoSeven is not approved for this purpose.
AquaGene is hoping to produce a much cheaper rival product using tilapia, a fast-growing freshwater fish widely farmed for food. Maclean has now managed to produce several lines of transgenic tilapia that produce human factor VII.
His team added a genetic switch from the tilapia to the human gene. This ensures that the gene is switched on in the liver of modified fish, and the protein secreted into the blood.
"Each millilitre of human blood has about 500 nanograms of the protein. We were able to match that yield in the blood of our fish," says Maclean. He hopes to produce tilapia that will make 10 times that level within a year.
Silkworm larvae
The next step will be to convince regulators that the fish-derived protein is the same as the human form, and that it is safe. The researchers have already tested it on samples of blood taken from patients with haemophilia, but many more studies will have to be done.
Other groups are exploring rival ways of producing proteins, from plants and chicken eggs to silkworm larvae and cattle, but Maclean thinks fish are a serious contender.
There is no evidence that any disease can be transmitted from fish to humans, for starters. Transgenic fish are also relatively cheap and easy to make, whereas it can cost millions to produce transgenic cattle.
Because tilapia breed so quickly, production could easily be adjusted to meet demand. "But escape is a concern," says John Matheson of the US Food and Drug Administration. For commercial production, transgenic tilapia could be grown in contained facilities.