Ready for the off

As the first biogeneric products gear up for launch on western markets, Ian Shine takes a closer look at this emerging market.

With patents for the earliest biopharmaceuticals beginning to expire, the first legally manufactured alternatives to some of the big brand-name drugs are forecast to hit the North American and European markets by 2006-2007.Despite being long hindered by a lack of regulatory framework, the biogeneric market in Europe and the US is expected to see exceptional growth and rapidly reach billion-dollar levels, as some products follow 'abbreviated routes to market'. The first biogeneric products to be launched onto these markets are likely to include erythropoietin, recombinant human growth hormone and recombinant human interferon.

As with any generics, the major market driver for biogenerics is their lower price. This is expected not only to encourage consumers to purchase generic alternatives, but also to receive support from governments and healthcare providers seeking to reduce expenditure on therapeutics.

cost reduction

According to a new report by market research company Frost & Sullivan (F&S), Strategic Analysis of the World Biogenerics Market, in the US, where healthcare is privately funded, not only the government, but organisations such as the Centers for Medicare and Medicaid Services and healthcare insurance providers are focused on reducing the costs of expensive biopharmaceuticals through the use of generic alternatives. This is expected to act as a stable driver to the biogenerics market from 2005 to 2011.

F&S industry analyst Himanshu Parmar believes the markets in Europe and the US have the potential to generate sales of US$16.39bn by 2011.

Several of the substances due to come off patent over the next 10 years are among the top-selling biopharmaceuticals. 'A major patent due to expire during the forecast period is Neulasta. (filgrastim), a human G-CSF, manufactured by Amgen, the patent on which is due to expire in 2007,' says Parmar. 'The interferon group of products for the treatment of multiple sclerosis and hepatitis also represents significant potential for biogenerics manufacturers.'

Other recent 'blockbuster' biopharmaceuticals to have come off patent include Amgen's Epogen (erythropoietin), for anaemia, in 2004 in the EU (2005 in the US), and Eli Lilly's Humulin for diabetes, also in 2004.

However, Parmar is quick to point out that high manufacturing costs for biologics compared with conventional small molecule drugs present a challenge to biogenerics manufacturers. 'The most successful participants are likely to be those that develop their own proprietary expression systems to minimise costs, and above all, ensure that products are bioequivalent and produced to full cGMP standards'.

Biogenerics are already available in developing regions, such as India and China, where there is less rigorous regulatory guidance regarding clinical testing. With regard to the US and Europe, Parmar predicts that 'once regulations are clearly established, a flood of biogeneric alternatives will hit the market soon after the expiry of each blockbuster patent'.

The establishment of such concrete guidance is getting closer and closer, particularly in western Europe where the European Medicines Agency (EMEA) is offering an abbreviated route to market by accepting Market Authorisation Applications (MAAs) for biogenerics that show 'proven biosimilarity in place of clinical trials'.

In the US the regulatory agencies are also turning their attention towards developing tools and procedures to assess biosimilarity without compromising drug safety.

But with multi-billion dollar revenues at stake, biopharmaceutical originators are not resting on their laurels. They are responding rapidly to the threat of biogenerics by reformulating existing products in order to maintain their market advantage by finding new disease indications, alternative delivery methods or new patient populations.

IP battles

They are also engaging in high-level intellectual property (IP) battles, similar to that raised by Pfizer against Eli Lilly and Icos over the use of PDE-5 inhibitors in their erectile dysfunction drug Cialis, which is marketed as a longer-lasting alternative to Viagra. The European Patent Office's decision to reject Pfizer's claim, does not bode well for companies hoping to counter biogeneric competition through such routes - something Amgen also found out in 2004 when a British court ruled its patent claims against Trankskaryotic's generic version of its Epogen drug to be 'unjustifiably broad'.

The company has since adopted a different tactic regarding Neulasta, having reformulated it with a more effective dosing regime under the brand name Neupogen (pegfilgrastim), the patent on which is valid until 2015.

As the markets in Europe and the US look set to open up, all the signs seem to point to a biogenerics boom, and with low levels of competition expected in the initial phases, it could be that the quickest movers will reap the biggest rewards.