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 The leading players in so-called "plantibodies" include San Diego's
Mapp Pharmaceutical, which garnered global attention for an
experimental Ebola drug given to two American medical workers, as
well as companies like Germany's Icon Genetics, Canada's PlantForm
Corp, and Delaware-based IBio Inc. All of the privately-held
companies are working to produce antibodies, protein drugs and
vaccines in fast-growing plants.
These companies hope the lower cost of plant-based production -- in
some cases as little as one-tenth the expense of conventional
antibody manufacture -- will eventually capture the attention of
larger drugmakers. Big pharmaceutical makers have yet to embrace the
technique after spending hundreds of millions of dollars on their
current manufacturing lines.
Industry experts say large drugmakers also need evidence that the
process can pass muster with regulators who have yet to approve a
biotech drug produced completely from plants.
"I think the interest will come," said Victor Klimyuk, chief
operating officer at Icon Genetics. "It's typical that the Big
Pharma industry is very conservative in what they establish and what
they invest in."
Bayer AG in 2010 joined with Icon to launch early-stage human trials
of a cancer vaccine grown in tobacco plants, but the larger
healthcare company has since dropped out.
Bayer declined to comment on why it decided not to pursue the
venture. Icon's Klimyuk said Icon is seeking a partner to move the
personalized vaccine into mid-stage trials.
"Our technology can complement standard manufacturing techniques,"
Klimyuk said. "It may work best when speed is required or when
flexibility is required ... to manufacture vaccines for an epidemic
or for fast, reliable production."
FROM METAL VATS TO GREENHOUSES
Antibodies are proteins used by the body's immune system to block
the path of foreign, potentially damaging invaders.
There are around 30 antibody-based drugs on the market in the United
States - including blockbuster cancer therapies such as Avastin and
Rituxan, both from Roche Holding AG. They are all produced from
mammalian cells, often from hamsters, that are cultivated in large
stainless steel vats.
"The technology in use now is very established and extremely
efficient … the big companies have made those investments and
adopted those systems," said Michael Kamarck, a biotechnology
industry consultant and former manufacturing executive at Merck & Co
Inc, referring to mammalian cell cultivation. "But if you are a
small biotech with a great idea, it might make sense to use the
tobacco plant to quickly produce antibodies for testing."
So far, the one successful venture into plant-derived drugs is a
U.S.-approved therapy for rare disease made by Israel's Protalix
Biotherapeutics, and marketed with Pfizer Inc.
The drug, Elelyso, is an enzyme produced from genetically engineered
carrot cells, but the cells are not reproduced in the plants. They
are replicated in a closed system using disposable plastic bags.
"We actually use cell culture - carrot cells or tobacco - in a way
that is similar to what is done in growing mammalian cells for the
biotech industry," said Protalix CEO David Aviezer.
He said the method - which Protalix is using for a range of
experimental drugs - is less expensive than producing drugs from
mammalian cells, but has the benefit of a clean-room environment
that regulators expect to see and are familiar with.
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The U.S. Food and Drug Administration has signaled some of its
concerns over plantibodies, including the need for manufacturers to
demonstrate that the source plant produces a consistent product.
In draft guidance from 2002, the agency also cited the potential for
the plant to express an allergenic or toxic compound and the need to
ensure that plant propagation is contained.
Pfizer, in an emailed statement, said it is not focusing on
producing drugs in plants. Gilead Sciences Inc and Amgen Inc, the
world's two largest biotechnology companies in terms of revenue,
said they had no information on the topic. Genentech, the biotech
arm of Roche, said it does not manufacture proteins from plants.
"Developing new drugs is a very expensive and risky business,' said
Qiang Chen, a professor at Arizona State University currently
researching the use of plant-farmed antibodies against the West Nile
virus. "I understand why they don't want to jump into new technology
that will make their lives potentially more risky."
A LONG WAY
Executives deeply involved in plantibodies say their work has come a
long way toward viable production.
"Fifteen years ago there were a number of companies involved, but
none were particularly successful," said PlantForm CEO Don Stewart.
"Yields were not that impressive and time lines to development were
quite long."
Mapp's drug, ZMapp, consists of a "cocktail" of antibodies produced
in tobacco plants at Kentucky BioProcessing, a unit of cigarette
maker Reynolds American. The process involves inserting
antibody-coding genes into the plant and growing them inside the
leaves, which are then harvested and ground up to extract the
antibodies.
PlantForm's Stewart estimated that for some protein drugs, the cost
of plant-based production could be one-tenth the cost of traditional
biotechnology manufacturing.
That could help poor countries like Liberia, among the hardest-hit
in the current Ebola outbreak, as well as developed nations where
healthcare costs are outpacing economic growth.
"We see it having pretty broad applicability," Stewart said. "The
cost of these drugs is a huge burden on healthcare systems in the
first world, particularly drugs for oncology and chronic disease."
(Reporting By Deena Beasley; Editing by Michele Gershberg and John
Pickering)
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