GTC Biotherapeutics (fka GTCB)

[DB9]

Latest transgenic rabbit-milk drug results positive.

22/08/2007 - Positive interim Phase III trial results for an experimental new transgenic rabbit-milk anti-inflammatory drug has prompted its developers to halt the placebo arm and treat all patients with this promising new therapy.

The drug, Rhucin (recombinant human C1 esterase inhibitor), is a human protein being to treat acute attacks of hereditary angioedema (HAE), a rare disease characterised by painful swelling of soft tissue.

Rhucin is fairly unique in that it is developed from a therapeutic protein produced in the milk of rabbits which have been engineered to carry and express the gene of interest in the mammary glands. The protein is collected using the proprietary technology of its developers, Dutch biotech company Pharming.

Only one such transgenic animal-derived drug is currently available on the market, GTC Biotherapeutics' goat-derived ATryn - which was approved last year as an anticoagulant to treat a rare congenital disease - and these latest trial results will bolster Pharming's bid to make its drug the second on the market.

Pharming announced this week that early results in a European placebo-controlled study designed to evaluate the efficacy and safety of Rhucin, showed that none of the patients taking the drug suffered a relapse of their HAE attack, nor any treatment-related adverse events.

These results reflect those from earlier studies, said the firm, who will be presenting the data in detail on August 30th at an analyst meeting in London.

"Based on the results and after consulting with the independent data monitoring committee, the Company has decided to discontinue further randomised treatments within the clinical study for methodological and ethical reasons…All investigators have been informed", Pharming said in a statement.

The company is pushing to have Rhucin approved and launched in Europe by the end of this year and said it has now included this latest analysis in its dossier submitted to the European Medicines Agency (EMEA) to further support its request for marketing authorisation.

While Pharming awaits a decision from the European regulator, it is also preparing to apply for US Food and Drug Administration approval (FDA) for Rhucin. An additional trial is required for the US application, which is currently ongoing but expected to be finished within the next few months, with the application to be submitted later this year. Pharmaing said it has now also submitted data from this latest analysis to the FDA to help its case.

Meanwhile, in July Pharming was advised that its five facilities used in the manufacture of Rhucin complied with the standards of good manufacturing practices (GMP), following inspections by the EMEA. The GMP approval was the first in the world for a transgenic rabbit facility.

Pharming chief commercial officer Rein Strijker told in-PharmaTechnologist.com at the time that the GMP success indicated a change in thinking and showed there was a move towards greater acceptance of transgenic animal-derived drugs.

"Many people in the past have questioned whether we can use animals to make drugs and often said we could not get to the stage where authorities would approve to GMP standards. This is proof that the authorities are satisfied with our production using animals. This is quite an achievement."

A new area in the drug world, transgenic drug-producing animals have been wrought with controversy and ethical debate, but according to Strijker the technology is more cost effective than conventional protein-producing mechanisms and has a lot of potential in the biopharmaceutical industry.

"Milk is very rich in proteins and mammary glands are good at producing high amounts in a high quality."

The transgenic rabbits are able to produce between 10 and 12 grams of protein per litre of milk, he said. This is compared to highly optimised cell cultures that can typically generate 0.2 to 1 grams of protein per litre of culture medium.

The high protein levels were achieved by including an extra bovine milk-specific promoter sequence (alpha-S1 casein) functionally linked to the gene encoding human C1 inhibitor. Rabbits can produce up to 10 litres of milk a year. Scaling up was an easy process, said Strijker.

Meanwhile, other companies active in the transgenic arena include US firm Hematech, owned by Japan's Kirin Brewery, which is focusing on human antibody-producing cows that will be used for the development of large quantities of polyclonal antibodies, while US-based Avigenics is pursuing avian transgenesis for treatments in oncology, infectious disease and autoimmune disease.

The use of animals in the production of biopharmaceuticals is clearly an exciting and emerging new field being explored by many cutting-edge firms - could breakthrough drugs using such technologies be the milky way forward?
http://www.biopharma-reporter.com/news/ng.asp?n=79169&m=1BPR822&c=ukpsipxgnfzvqja