Posts Tagged ‘glucocerebrocidase’

…and here they come…

8 February, 2010

…Big Pharma, to the biopharming revolution, that is.  Following on from earlier news about Protalix’s glucocerebrocidase successes, comes this latest snippet from Nature Biotechnology:

Pfizer stakes a claim in plant cell–made biopharmaceuticals

Mark Ratner

On December 1, Pfizer became the first big pharma to commit to take to market a late-stage biologic drug produced in plant cells. It acquired rights to taligurase alfa, a form of the enzyme glucocerebrosidase in development for the treatment of Gaucher’s disease, from Protalix Biotherapeutics in Carmiel, Israel. Protalix has completed phase 3 studies and has submitted a new drug application for the drug, also known as prGCD, eyeing US marketing approval in 2010. At the request of the US Food and Drug Administration (FDA) last year, the company has already begun supplying prGCD to patients in the US under an expanded access program and similarly to patients in the EU under a compassionate-use protocol [my emphasis – Ed].

Very interesting development, this: while Bayer led the way in acquiring plant expression vector maestros Icon Genetics a couple of years ago, there has not been much interest by Bigger Pharma in getting hold of the plant-expressed biologics startups – but expect things to change, starting now.

Ratner goes on, quoting Yuri Gleba of Icon / Bayer:

…Icon’s Gleba acknowledges that Protalix’s success in product development with prGCD shows they have a keen business sense. “If you are not strong on one side you have to compensate by being excellent on another, and by all accounts, they are,” he says. The deal with Pfizer and the approval of prGCD “should open the floodgates, in my opinion,” he says. “It is by far the most significant development in the plant-made pharmaceuticals arena right now.”

The floodgates are opening; Big Pharma is at the door – finally!

Plant therapy creeping in….

8 September, 2009

The August issue of Nature Biotechnology has a very interesting snippet of news – from two points of view. From a strict virology point of view, it is interesting that commercial production of a therapeutic enzyme in an industrial plant can be shut down because of infection of their mammalian cell line with a contaminating mammalian virus.

From the second point of view…well, our lab has a very strong interest in producing recombinant proteins (and especially candidate vaccine proteins) in plants – and here is a story showing just why plants may be a really good alternative means of production for pharmaceuticals.  First, the story:

Nature Biotechnology 27, 681 (2009) doi:10.1038/nbt0809-681a
Virus stalls Genzyme plant by Victor Bethencourt

Genzyme of Cambridge, Massachusetts, faces millions in lost revenue from its top-selling specialty drugs Cerezyme and Fabrazyme as result of a viral contamination at its Allston, Massachusetts plant. The company has announced that it will temporarily shut down the facility owing to a bioreactor contamination with Vesivirus 2117 [my emphasis – Ed], which does not cause human infections, but impairs growth of the biologics-producing Chinese hamster ovary (CHO) cells. It reportedly originated from tainted nutrient medium and belongs to the same strain that caused delays at the Allston site and its European biologics plant in Belgium last year. Genzyme anticipates supply constraints of Cerezyme (imiglucerase), a treatment for Gaucher disease, and Fabrazyme (agalsidase beta), used to treat Fabry disease, while the facility shuts down for 6 to 8 weeks to allow decontamination.

OK, really interesting, that: a vesivirus – genus Vesivirus, family Caliciviridae, nice link here for structure, and here for Genzyme’s press release – that is being transmitted around via cell culture media, between manufacturing plants.  One of the perils of using mammalian cells to make things…!

Vesivirus via kwout

The article goes on:

…With sales of $1.2 billion for Cerezyme and $494 million for Fabryzyme in 2008, analysts estimate the manufacturing crisis will result in $100–300 million in lost sales. The US Food and Drug Administration (FDA) has contacted rival manufacturers Shire of Basingstoke, UK, and Carmiel, Israel–based Protalix, who have enzyme replacement therapies for Gaucher disease in clinical trials, to file treatment protocols, which would allow physicians to use their drugs ahead of approval.

And of course, Protalix makes its glucocerebrocidase in cultured carrot cells, in disposable “bioreactor bags”….  In completely defined chemical media, with no risk of plant virus contamination – not that plant viruses can infect cultured plants cells, by any means short of being shot in on gold beads!  Their web site Press Room page had this to say as of 25th August:

Aug. 25, 2009 (Business Wire) — Protalix BioTherapeutics, Inc. (NYSE-Amex:PLX), announced today that it has received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for prGCD, the Company’s proprietary plant-cell expressed recombinant form of glucocerebrosidase (GCD) for the treatment of Gaucher disease.

I wrote the following about Protalix after attending the Plant-Based Vaccines and Antibodies Conference in Verona in June this year (September issue of Expert Rev Vaccines, 8: 1151-1155, 2009):

“Einat Almon-Brill (Protalix Biotherapeutics, Israel) described their production of recombinant human glucocerebrosidase (rGCD) as a therapy for Gaucher disease, caused by a hereditary mitochondrial defect.  They used a contained disposable bioreactor system with suspension-cultured carrot or tobacco cells, and claimed there were no mammalian cell culture risk factors; they obtained uniform glycosylation, and the exposed mannose allowed rapid macrophage uptake.  The rGCD half-life was twice as long as commercial product, and had been trialled in Europe, Israel, South Africa, and North and South America.”

I wish I’d bought stock…or had the money to, or knew how to!  The time of plant-made pharmaceuticals – PMPs – is coming.

Be ready…B-)