The total market potential for FIX products is estimated to be in excess of $600m worldwide per year as Haemophilia B is a genetic disease which affects one out of 34,500 men.
Injected several times per week to several times per month, current FIX replacement injections cost up to $125,000 annually.
Furthermore, these expensive shots, which provide only temporary relief, may include complications, including blood clots in the vein and development of antibodies that block the activity of the injected FIX, making a non-intravenous delivery system look very appealing.
In-Pharmatechnologist.com spoke to Adam Jones, a British 34-year-old patient of Haemophilia B whose severe condition requires him to be injected weekly with 5,000 international units, about the change a non-intravenous delivery system would make to his life.
"It would make a fantastic difference if I could take FIX orally, it would remove the need for needles, making it easier and safer for me and my family," he said.
"Currently I can't even travel with many airlines because they won't allow me to have needles on board the airplane."
However, given the rarity of the disease, the fact that the quality of life of Haemophilia B patients would be improved doesn't automatically make the research of non-injectable alternatives an attractive business proposition for drugs companies.
"When you are treating haemophilia, you are not just treating haemophilia, so think of how much money the National Health Service [in the UK] would save through an effective non-intravenous treatment," Mr Jones pointed out, arguing for more government funding.
"Because of my bleeds I also have to be treated for arthritis, I need to see a physiotherapist and may even need a wheel chair - all this cost money."
The money for the research subcontract comes from a five year grant totaling $10m UNL has received from the American National Institutes of Health entitled 'cGMP Recombinant FIX for IV and Oral Hemophilia B Therapy'.
The current subcontract with BioSante is for the first year of the grant and, if warranted, BioSante can apply to renew the subcontract in subsequent years, with a total possible value to the company of $1.25m over five years.
Wyeth Pharmaceuticals, a division of Wyeth, is just one of the main pharmaceutical companies who already produce a recombinant coagulation FIX.
Its BeneFIX Coagulation Factor IX (Recombinant) and ReFacto Antihaemophilic Factor (Recombinant) are indicated for the control and prevention of hemorrhagic episodes in patients with Haemophilia B, including control and prevention of bleeding in surgical settings.
Likewise, Aventis is also a big player in the market with Mononine, manufactured from pooled human plasma.
But Biosante's fiercest competition is set to come from Avigen's development pipeline, whose first non-biological (i.e. non-gene therapy, non-protein) approach for the treatment of haemophilia, AV513, represents the first such agent to treat multiple bleeding disorders (Haemophilias A and B and potentially FVII deficiency and severe von Willebrand's disease).
Crucially, AV513 has the potential to be the first therapy for haemophilia to be delivered orally and has already been tested and demonstrated to significantly improve clotting time in both large and small animal models of haemophilia.
Biosante will incorporate its proprietary calcium phosphate nanotechnology (CaP) with plasma derived or recombinant FIX, where preliminary studies indicate this can be done with greater than 75 per cent efficiency.
The firm anticipates comparable efficiency from the CaP-transgenic-FIX formulations, which are currently in progress.
"In our research laboratories, bench-scale CaP particles are synthesised in a very simple process involving physical mixing of inexpensive calcium and sodium salt solutions at room temperature to produce calcium phosphate crystals," Tulin Morcol, study director of the subcontract awarded to BioSante, told In-Pharmatechnologist.com.
"We are currently in the process of designing large scale manufacturing of CaP placebo and CaP-active drug formulations."
The basic principle of formulating therapeutic drugs with CaP particles is the co-precipitation of the drug molecule of interest with the inorganic salt components of calcium phosphate during the CaP synthesis.
Most proteins and protein-like molecules have high affinity for calcium phosphate either through electrostatic charge interactions, or through their divalent-metal binding domains, or even through simple salting-out mechanisms.
This leads to physical adsorption of the drug on the calcium phosphate particle surface or entrapment of the drug inside the particle precipitates.
Biosante cites years of accumulated pre-clinical data indicating that the active drug molecule formulated with CaP retains its functional (or therapeutic) activity.
What is more, stability of protein drugs is significantly improved upon formulating with calcium phosphate, which is a natural component of bone and is on the FDA's GRAS (Generally Regarded as Safe) list.
Depending on the desired route of administration, CaP-active drug combination can be complexed with other specific GRAS materials to improve the bioavailability or therapeutic effectiveness of the drug.
BioSante's CaP nanoparticles also have successfully passed the first stage of toxicity studies for administration orally, into muscles, under the skin and into the lungs by inhalation.
Although the direct material cost of CaP itself is very inexpensive (approximately $100-150/kg), the company says the manufacturing cost of the CaP-drug formulation will largely depend on the cost of the drug itself and specific process parameters designed for each individual drug depending on its physical, chemical and molecular properties.
In the case of FIX, Biosante believes it can develop an easier, more affordable non-intravenous therapy, particularly for hemophiliacs in developing countries.
The company has successfully completed preclinical trials of CaP formulations for long-acting insulin injections, inhaled insulin and oral insulin, among other proteins.