Ten Years of Enzyme Replacement Therapy

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Genzyme Therapeutics celebrated 10 years of enzyme replacement therapy in the UK at its new offices in Oxford on 20 September 2002. Doctors and patients spoke about the progress of Gauchers disease over the past decade and Henri Termeer, Chief Executive Officer of Genzyme Corporation, gave his reflections.

Malcolm Johnson, Vice President and General Manager of Genzyme Therapeutics UK welcomed guests including doctors and staff from Addenbrooke's Hospital, the Royal Free Hospital and Great Ormond Street Hospital. Susan Lewis, Don Tendell, Dina Katz and other members of the Gauchers Association also attended.

'Genzyme was founded in 1981,' explained Mr Johnson. 'And shortly afterwards it acquired Whatman Biochemicals Ltd which was based in Maidstone. Part of the process of producing the enzyme glucocerebrosidase for Gauchers disease is to purify the enzyme which is a protein. The company had the facility to do this and I had already been working there for 10 years.

'In 1989 Ceredase became available in the USA to seriously ill patients prior to full approval and in 1990 Ceredase was given to sufferers outside the US on a named patient basis. In 1991 the FDA granted marketing approval for Ceredase in the US and approval in the UK came in 1994. Cerezyme received FDA approval in 1994 and European approval in 1998.'

Reflections Henri Termeer described his determination in the early days to produce enzyme replacement therapy for Gauchers disease even though many of his colleagues at that time said that the drug would never lead to success.

'Those early days of Genzyme and enzyme replacement therapy were pioneering. It needed people who said I've just got to try this. However the real pioneer for Gauchers disease is Dr Roscoe Brady who had been working on making the therapy work since 1966 at the National Institutes of Health (NIH) in Washington DC. It was a slow and laborious process.

'Henry Blair, who had been producing the enzyme for Roscoe Brady at NIH, decided to found Genzyme in 1981 to produce the enzyme for a research project. I joined Genzyme two years later.

'The first results of the enzyme on eight patients were not good but in 1984-85 the enzyme was manipulated with good results. 'The first patient to receive the mannose-terminated version of the enzyme was a young boy whose mother wanted to give him one last chance before his spleen was removed. 'In three months the boy showed a response but every time they ran out of enzyme and his treatment stopped, the boy deteriorated.'

Raising Finance was Formidable

'The hurdles to raise more finance for the trials were formidable,' stated Mr Termeer. 'Not least was the fact that human placentas were the source of the enzyme and to provide a year's dose for just one patient, more than 22,000 placentas were needed.

'To overcome this, Genzyme built a plant in France to take unwanted placental tissue which would have otherwise been burnt and extracted the enzyme. At one point 35% of all placentas from the US were passing through the French plant. Ceredase was the only drug made from placentas which the UK Government allowed to be used in Britain.

'The rare incidence of the disease also made potential investors sceptical. Mr Termeer said that the turning point was when the mother of the boy who had benefited from the treatment came with him and his colleagues to an investors meeting. The mother, who was eight months pregnant, was very convincing. The investors then came up with the money.

'Genzyme raised $10m so that they could produce the enzyme for a trial on 12 patients. This was in 1987, 17 days before the stock market slump. If the money had been delayed, I don't know what would have happened.'

Mr Termeer described 10 years of adventures in developing Ceredase and then Cerezyme (the recombinant form of the enzyme) . When Ceredase received FDA approval in 1991, Genzyme started building a plant to produce the recombinant drug.

'At that time although we were collecting about a million placentas a year we knew we could not produce enough enzyme for all the patients who needed treatment. In the end enough Ceredase was produced to support almost 1,000 patients around the world before they were moved over to Cerezyme.

'Overcoming the hurdles has built a great faith in me that things can be done to help people with rare diseases. It will drive my optimism for ever and my belief in achieving things that seem impossible.

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Source: Gauchers News April 2003.
© Copyright Gauchers Association 2003.