Drug-making plant blooms

(Nature-08 May 2012) Approval of a ‘biologic’ manufactured in plant cells may pave the way for similar products.

It was midnight when an anxious Ari Zimran finally got the phone call for which he had been waiting. The news couldn’t have been better: the drug he had worked on for nearly a decade had just been approved by the US Food and Drug Administration (FDA).

Zimran, was not the only one celebrating the company’s success last week. Biotechnologists around the world cheered, because Protalix’s Elelyso (taliglucerase alfa) is the first biological drug for human use that is manufactured inside modified plant cells.

Drugs that are based on large biological molecules — known as biologics — have been produced inside genetically engineered animal cells, yeast and bacteria for more than two decades. Insulin has been made by genetically modified Escherichia coli bacteria since 1982, and by 2010, the global market for such therapies had reached about US$149 billion.

Since the early 1990s, some researchers have been developing plants that could act as cheaper factories for biologics. Plant-cell cultures are also attractive because they require less precise conditions for growth than animal cells. But efforts to exploit plants in this way have lagged, in part because companies and investors were wary of this unfamiliar production method.

Protalix was strategic in targeting a rare heritable disorder called Gaucher’s disease, because current means of producing treatments for it have fallen short. The disease is caused by an enzyme malfunction that results in the accumulation of fat in cells and organs, with symptoms ranging from bone deterioration to anaemia. Two existing drugs compensate for the enzyme deficiency, but they can cost up to $300,000 per year in the United States, and drug shortages in recent years have left some patients in need of hospital care.

“It’s really the regulatory hurdles and costly clinical trials that are a barrier.”

Structurally, Protalix’s Elelyso resembles one of those drugs: Cerezyme, made by Genzyme in Cambridge, Massachusetts. Cerezyme is produced in modified hamster cells, which require regulated temperatures, a complex growth solution and an environment scrubbed free of the viruses that infect hamsters and humans alike. These factors contributed to manufacturing problems that dogged Genzyme last year, limiting supplies of Cerezyme.

Protalix’s solution is to take a normal version of the human gene affected in Gaucher’s disease and introduce it into carrot cells, which are more robust than hamster cells, and then extract the enzyme they make. The lower production overheads will allow the company to sell Elelyso for just 75% of the price of Cerezyme, the most popular drug on the market, says David Aviezer, Protalix’s president.

Source: http://www.nature.com/news/drug-making-plant-blooms-1.10604