April 27, 2006 – Researchers are busily ferreting out new agents that make drugs more effective. And when a drug works better, less of it is needed. But as more of these drug boosting agents — known as adjuvants — are put to use, a thorny medical problem has appeared. BioSante Pharmaceuticals thinks its calcium phosphate nanoparticles might be able to clear the way.
BioSante researchers say a specially formulated calcium phosphate, or CaP, can deliver treatment without the allergic reaction often associated with the aluminum salt derivatives in adjuvants. The company reported on Monday that preclinical animal studies demonstrated that its BioVant, a calcium phosphate-based mix of adjuvant and the experimental H5N1 antigen, was able to generate a doubling of the immune response in mice.
For drug developers, it’s a new avenue to explore in the quest to take a limited amount of vaccine and spread it among large populations fighting a potential pandemic.
“A vaccine with an adjuvant included may allow for better efficacy and lower doses per vaccination, which may help to prevent shortages,” said BioSante CEO Stephen Simes. “More importantly, addition of an adjuvant may enable more people to produce an immune response to protect them from disease.”
Adjuvants are considered particularly crucial for experimental bird flu vaccines, where only thin supplies would be available to protect people. In a recent report in the New England Journal of Medicine, an experimental vaccine developed by Sanofi-Aventis delivered without an adjuvant was effective in only slightly more than half of the subjects and only at the highest doses. Their goals are still somewhat inexact, but BioSante is hoping that much smaller doses will be able to reach much larger populations more effectively. Some new adjuvant-enhanced vaccines have demonstrated effectiveness at only a fraction of the amount typically needed to boost the human immune system.
BioSante combines tiny calcium phosphates with reagents to “come away with particles of defined size and other physiochemical characteristics,” said Steve Bell, vice president of research and preclinical development. The calcium phosphates that BioSante uses are 100 to 1,000 nanometers in size. Because they are natural materials that appear in bone and teeth, BioSante says they also don’t present any risks to the body, allowing researchers to combine them with therapeutics that can be delivered in new ways.
Like several other early-stage drug developers, BioSante has also been exploring how nanobio techniques can help improve the delivery of existing therapies. The Lincolnshire, Ill.-based company has several calcium phosphate programs underway, including one for insulin and a new way to deliver therapies to hemophiliacs.
“We have a few patented formulation procedures that involve a common theme: the ability to combine the active material, which could be a drug or small molecule or peptide or protein or nucleic acid or antigens derived from pathogens, with the inorganic salt in solution,” says Bell.
“In toto,” he added, “it’s a very rational science. It’s taking nano-sized combination particles that have been around forever that no one has ever looked at.”
One of the other advantages of calcium phosphate, said Bell, is that it allows a therapy to be delivered in various ways: inhaled through the nose, anally or injected, to name a few.
BioSante is one of several companies exploring new uses of calcium phosphate. Brian Genge, a researcher at the University of South Carolina, combined early experience working with his father pouring cement with later scientific work on bone formation to come up with a calcium phosphate paste that has potential in a variety of medical applications. Competitive Technologies (CTT) of Fairfield, Conn., licensed the technology.
“I guess the technology arose from the premise that we wanted to use the actual minerals involved, something that self hardened, and that could do it without generating heat that is deleterious to the body,” said Genge, who has worked with the Department of Defense on ways to speed the healing process. The nanomaterial starts dry and is mixed with a small amount of water. The resulting material is “twice the compressive strength of concrete in 15 to 20 minutes.”
A company has licensed the human spinal application of the work and Genge is researching new uses that range from cranial facial surgery and repair to cosmetic surgery to bone augmentation.
Calcium phosphates offer advantages in the commercialization process, says CTT’s Aris Despo, senior vice president of life sciences. Because they are using natural materials, the FDA will give the new processes an accelerated review as a medical device, cutting down the time and expense of getting a final decision from the agency.
For BioSante, a public company which has been raising much of its money from government contracts and grants, the next step is to move into the clinic as soon as possible to test the technology on people. It is also exploring potential partnerships with deep-pocket biopharma companies to take the nanotechnology further down the pipeline.