Canadian firm SemBioSys Genetics last week announced that its proprietary plant-produced insulin has been shown to be indistinguishable from human insulin, opening up a whole new potential source of the hormone.
The findings could have massive implications for the insulin market, currently dominated by only three companies - Eli Lilly, Novo Nordisk and Sanofi Aventis, recording blockbuster insulin sales of over $7.2bn (€5.6bn) in 2005.
The company believes manufacturing insulin using its commercial plant safflower could reduce capital costs compared to existing insulin manufacture by up to 70 per cent, and product costs by 40 per cent or more. In November the company announced a manufacturing deal with Canadian firm Cangene for the processing and purification of it plant-based insulin.
SemBioSys has been working with the transgenic plant for five years, and its latest results show that plant-derived insulin is identical to human insulin both analytically and physiologically. The product was found to be functionally equivalent to Eli Lilly's Humulin and U-S-P insulin treatments.
The company has been able to achieve a 1.2 per cent accumulation of insulin within the seed protein of the plant, exceeding its commercial target. At this level of insulin production, one acre of safflower would give a yield of over one kilogramme of insulin - enough to supply 2,500 patients for an entire year.
The key market for insulin is for the treatment of diabetes, a disease predicted to become increasingly widespread over the coming decades. In 1985 an estimated 30m people worldwide suffered with diabetes; by 2000 this had risen to 150m, and the growth is expected to continue, hitting 350m by 2025. By 2010 the global market for insulin is projected to be worth around $11.8bn, and demand for insulin is predicted to rise from around 5000 kg to 16000 kg.
"The industry now has three major manufacturers of insulin, and would seem ripe for more entries," Philip Home, chair of the International Diabetes Federation Clinical Guidelines Task Force, told In-PharmaTechnologist.com.
"Insulin use has tripled in Europe in the last 12 years, and with the continuing rise in numbers of people with diabetes, earlier and earlier use of insulin, and people living longer with the condition this market is in for further expansion despite competing new products to lower blood glucose."
SemBioSys hopes to submit an investigational new drug (IND) application for its product later this year, and initiate clinical work with the insulin before the end of 2007. The company has a great deal of confidence in their product, and predict that its insulin candidate could reach the market by as early as 2010.
"We clearly have defined and delineated a business development process that calls for us to begin discussions with major players in the field both here and outside North America," said SemBioSys president and CEO, Andrew Baum.
"Now we have the data set we've described, we're in a position to have fairly serious discussions with potential partners."
As new delivery methods for insulin emerge, the demand for insulin is set to increase even further - inhaled insulin technologies, for example, require five to ten times as much insulin as injection methods.
"With respect to the injectable versus the inhalable insulin, right now our plans call for us to proceed first with injectable insulin because we can go very quickly with what we have into the clinic for Phase II trials and then into Phase III," said Baum.
"The injectable is relatively straightforward because the volumes are relatively small; the inhalable volumes are so much bigger that it's a bit more challenging to get there - although I think that by the time we would partner we would probably have that in place."
Current methods of insulin production rely on yeast (Saccharomyces cerevisiae) or E-scherichia coli genetically engineered to produce synthetic human insulin. These organisms are grown in large steel bioreactors, whereas SemBioSys' plant form will be grown out in the field.
This necessarily calls for extra safety measures to be incorporated into the manufacturing process, according to SemBioSys:
"We developed an assay system that screens for roughly 500 of the most commonly used agricultural chemicals and pesticides," said the company's chief scientific officer Maurice Moloney.
"These plants are well looked after, they're not simply planted and then left to grow by themselves - they're somewhat molly-coddled compared to your average agricultural plant."
Avoiding the Needle
Pharmaceutical heavy-weights Pfizer, Eli Lilly and Novo Nordisk have all recently been branching out and developing new needle-free methods of insulin administration. Pfizer's inhalable insulin product Exubera is a few steps ahead of Lilly's AIR Insulin System, currently undergoing Phase III clinical trials, and Novo Nordisk's AerX product is also in the final stages of clinical studies. There is also competition from US company Mannkind, whose inhaled insulin product Technosphere completed Phase III trials with Type 2 diabetes in September last year.
On top of this, news from Taiwan is that an insulin pill could also be on the cards providing patients with another potential treatment option. The idea of a pill for insulin delivery has been toyed with before; the problem is that drugs containing proteins (such as insulin) cannot withstand the acidic environment in the stomach and are quickly destroyed.
However, researchers from the National Tsing Hua University in Taiwan reported in this month's edition of the journal Biomacromolecules that they have found a way of encapsulating insulin in such as way as to protect it from the digestive fluids in the stomach and allow the hormone to reach the bloodstream.
Insulin was encased in a polymeric chitosan shell, and administered to rats that had been given drugs to mimic the effects of diabetes. The insulin-loaded nanoparticles were found to lower blood-glucose levels, whereas plain insulin delivered orally resulted in little or no effect.
However, very high doses of insulin were required for the glucose-lowering effect to be observed, and the rats had also been without food for 12 hours prior to receiving the drug. While there is clearly still work to be done on this new delivery technique, it represents another potential direction in the burgeoning insulin delivery market.