US chemicals company Aceto has broken cover and is now racing to develop a leading player in the market for generic versions of biologic drugs, even though the regulatory route to approval of these products is far from established.
Aceto has signed a deal with contract manufacturer Three Rivers Pharmaceuticals in a collaboration aimed at bringing three generic biopharmaceuticals to market in the US, Europe and Japan. The deal not only marks Aceto's entry into the biogenerics business, but will also be the first time that it supplies finished dosage forms in significant quantities.
Some of the biggest-selling biological drugs developed during the first phase of the biotechnology revolution in the 1980s - including hGH, interferon alpha and insulin - have already lost or will lose patent protection in the next few years. This opens up a market currently worth $30 billion (€23.4bn) and growing at 10 per cent a year, but only for those companies that can navigate the tricky regulatory route to market.
While the high cost of biologics (often tens of thousands of euros per patient a year) lends some urgency to the approval of biogenerics for healthcare budgeters, the regulators are finding it hard to deliver because production of biologic drugs has a touch of the arcane about it. This is mainly because, in contrast to chemically synthesized drugs, it is hard to develop quality standards for biologics. In turn, this means that quality standards that could prove 'bioequivalence' - the standard measure by which a generic is shown to behave in the same way as an originator drug, are lacking.
So regulators are left with a problem - how do you prove that a biogeneric is in fact identical to an originator molecule? And their decision is made the harder by suggestions that small changes in a biologic production process can have dramatic consequences on a product's safety and efficacy. One often cited example is the case of Johnson & Johnson's Eprex (epoetin), which was associated with 250 cases of a serious red blood cell disorder in the late 19990s, eventually blamed on changes in the handling and administration of the drug.
Because of these difficulties, biologics are approved on the basis of purity, potency and identity, rather than safety and efficacy as is the case with conventional drugs. In the eyes of the biotechnology industry, this distinction is crucial, as it means that a biologic must always be produced using an identical manufacturing process. This is very difficult for biogenerics companies to achieve, forcing them down the route of carrying out a full, expensive clinical development programme for their biogeneric.
Two years to market?
Regulatory discussions to develop appropriate ways of allowing biogenerics on the market, mainly centering on improved quality standards, are ongoing, and Aceto and Three Rivers are gambling that these will be resolved by the time it is due to bring its first products to market in 2007. They aim to file their marketing applications for the biogenerics in the US within a year.
Aceto and Three Rivers hope to accelerate the regulatory deliberations on biogenerics in he US by filing specific products for the Food and Drug Administration to deal with, in much the same way that a series of filings brought matters forward in Europe. The European Medicines Agency (EMEA) is currently looking at so-called 'biosimilar' versions of human growth hormone and interferon alpha.
While Aceto and Three Rovers have not yet divulged the identity of their three biogenerics, analysts expect that the first entrants into the marketplace are likely to be insulin and human growth hormone, at least in the US. This is because unlike other biological products, these drugs receive FDA approval under the standard New Drug Application (NDA) process. This may make it easier to secure generic approval as there is a tried-and-tested route to market, albeit for chemical drugs, via the Abbreviated New Drug Application (ANDA) route.
Len Schwartz, Aceto's CEO, limited himself to saying that one of the biogenerics "will compete with a brand name market that approximates $500 million (wholesale) in the US."
Under their agreement, Aceto will source the active pharmaceutical ingredients, manage the regulatory and quality control functions of production, and supply the final dosage form of the products to Three Rivers. The latter will file applications with the appropriate regulatory agencies and market the products in the US, Europe and Japan, with the two firms sharing revenues.
A recent report published by Cutting Edge Information, estimated that biogenerics would command more than $12 billion of the drug market by 2010.