For the first time, the US Food and Drug Administration (FDA) today has approved a drug produced in a genetically engineered plant cell. Among those cheering the news are scientists who have advocated ‘bio-pharming’.
The drug, Elelyso (taliglucerase alfa), soothes the symptoms in most patients of the rare lysosomal storage disorder Gaucher disease, which causes problems ranging from bone infections to anaemia. Scientists at the Israeli biotechnology company Protalix Biotherapeutics developed a method to create the human enzyme that these patients lack in carrot cells, by inserting a gene that encodes the protein into the cells. Patients treated with the resulting enzyme (taliglucerase alfa) in clinical trials fared at least as well as those given another enzyme-replacement therapy on the market, Cerezyme.
“It’s wonderful to have another option available,” says Rhonda Buyers, executive director of the National Gaucher Foundation in Tucker, Georgia. She hopes that Elelyso will help to prevent drug shortages like those in 2009 and 2011, when patients relied on Cerezyme alone. “People whose symptoms had been controlled for years were having bone issues and terrible fatigue, some went the hospital,” she recollects.
Manufacturers of the two other Gaucher drugs — Genzyme in the US and Shire in Ireland — produce their therapeutic enzymes in mammalian cells. Structurally, Elelyso resembles Genzyme’s Cerezyme, but it’s cheaper to produce because of the high maintenance that animal-cell cultures require. Further, viruses and other pathogens that contaminate mammalian stocks don’t threaten plan-cell cultures.
For more than a decade, researchers have been able to genetically manipulate plants so that they produce human enzymes. In 2006, the US Department of Agriculture approved of a chicken vaccine produced in plant cells. But assuaging concerns about plant-derived biologics for human use has proved much more difficult. Therefore, scientists and drug manufacturers developing other therapeutic enzymes, antibodies and vaccines in plants say that Elelyso’s approval may make the regulatory process more straightforward for them, and alert big pharmaceutical companies and investors to the potential profitability of plant platforms.
Before the FDA’s announcement today, Ritu Baral, a research analyst with Canaccord Genuity in New York, said, “If this drug gets approval it would be a huge proof of concept for the entire platform.” Although the company is poised to treat 2,000 patients in the United States, Baral says it’s uncertain what the US market will be because of brand loyalty to Genzyme and Shire. However, the fact that Elelyso will cost about 25% less than Cerezyme might sway buyers.
Sixty per cent of the profits from US sales will go to the pharmaceutical giant Pfizer, which made a deal with Protalix in 2009. However, as long as the Israeli government approves the drug, all profits in that country will go to Protalix. Israel represents a relatively large slice of the pie, as Ashkenazi Jews are disproportionately affected by the disease.
David Aviezer, president and chief executive of Protalix in Carmiel, is quite optimistic about the other carrot-made drugs in the company’s pipeline. Earlier this year, Protalix began to plan for phase I clinical trials on their protein to treat another enzyme-related disorder, Fabry disease. “This approval demonstrates a proof of concept for the power of this technology to make a large number of proteins,” Aviezer says. “We are ready to make many more.”