Dr J C Pompe

Dr J C Pompe
Discoverer of Pompe disease

About this blog

What you can read here is the story of the development of enzyme replacement therapy (ERT), the first effective treatment for Pompe disease. It is an incredible story, rich with events, characters and science. Above all, it is the story of an international community of scientists, doctors, patients and companies, working together towards a common goal.

It is not a story that features in Geeta Anand's book, The Cure , or the film based on it, Extraordinary Measures despite the fact that they are ostensibly about the development of ERT for Pompe ( you can link straight to the relevant articles covering the events described in the book and film here, here and here).

This blog represents my small attempt to set the record straight and to give the story back to its rightful owners - the international Pompe community. It is written here in roughly chronological order i.e. you'll need to start at the bottom of the April 2009 archive page and work your way up.

It is also a personal account and, although I've tried to make it as objective as possible, there is an inevitable degree of subjectivity. For that reason I have included contributions from other members of the worldwide Pompe community and would be delighted to receive more. Feedback is also welcome.

Search This Blog

Thursday, 7 January 2010

Oxford 2000- part 2

AGSD-UK's Oxford 2000 conference (part 2)

Aside from the researchers we also had a strong representation from Genzyme and Pharming (who were the sponsors of the conference). In attendance were Jan van Heek, Gene Williams, Willem va Weperen and Phillipe Houten (I'm guessing here -I forgot to write Phillipe's second name down - d'oh!).

The first two had attended an IPA executive meeting the night before and had expressed a desire to be more open and communicative with the patient community. I therefore gave them the opportunity to answer a few of the questions that have been in people's minds since the switch to the CHO method of production: are there any differences in the results for the two methods? what are the benefits to us? What are the time-scales for trials? What is the availability of enzyme?

Genzyme: ERT is working and this is very encouraging. The question for us now is how can enough enzyme be made for more trials and beyond. It is good to know that, from Genzyme's experience, it is possible to get Government/insurance to pay for such products.

It was a difficult decision to switch manufacturing from the rabbits to cell culture. We have not been good at communicating this and in future would like to work better with patient groups.

We know that the product works and now need to work on appropriate doses etc. Time lines are under review and more questions arise as we go along. We promise to publicise any changes.


Q: We know that the milk based enzyme is efficient and non-toxic. can it not be made commercially viable? There is as yet no data for the cell-based enzyme.

A: We have looked at the unpublished data from Y T Chen and our believe that both products will behave similarly is supported by the data. (A. Reuser commented that tests with mice had shown no differences, however there was no comparison with humans yet. As the two trials had been set up differently, it was difficult to make an exact comparison - the types of patient, doses etc. may have been different, amongst other uncertainties. Conclusion - there is no evidence that suggests that they don't work equally well.)

In June, in Boston, all sorts of experts convened and reviewed the data. It was concluded that more trials were needed to satisfy the requirements of the regulatory authorities.

Lots of enzyme is needed and manufacturing must be scaled up dramatically

Q: Will it be easier to produce commercial quantities using cell manufacture?

A: Easier and faster. We have 60 different people working on the Pompe programme. The uncertainties are that we have no manufacturing capacity yet and no regulatory approval yet.

Q: Why not do trials which would be approved quicker?

A: Can't do it until ERT is proved to work, to the satisfaction of the regulatory authorities. At the beginning we didn't know the dose that would be required. A lot of material is needed to be effective, therefore a large manufacturing capacity is required. At least 50 people working on doing that.

We decided that this way was faster, more durable and gave more product to get to patients.

The key now is to get trials started to get us to the first end point - regulatory approval.

We need to select patients, treat them and then analyse and present the esults. All that takes time.

We now understand the importance of getting timely information to patients.
We are meeting with the FDA in October to discuss the next trial.

Q: Is this just for the USA?

A: Our intention is that the data will be produced in such a way that it is acceptable to all the different authorities. It will be a multi-centre trial in around 5 locations - not confined to the USA. We will communicate details to patient groups via the IPA.

Q: What are the plans for future trials?

A: The constraint is supply of enzyme. There may not be enough until late 2001. this is under discussion and review. We are working hard on this issue.

Q: Is the switch to CHO the solution to the problem of enzyme availability or the cause?

A: The solution. It will be quicker.

Q: What will happen to the patients receiving the rabbit milk enzyme at the moment?

A: We met some of the patients in Rotterdam. We are committed to provide the rabbit enzyme to them until 2001 [implication was until CHO supplies are available - KOD].

Q: In the early days we were told that rabbits could produce enough enzyme, then that cows would be used. Is that off the agenda now?

A: We think that there will be enough CHO capacity to meet demand. The cow platform is being preserved and the rabbit line just in case the CHO production does not work. All you can do is to make the best decision you can on the basis of the available data - and at the moment that means CHO.

Q: Would it be better to develop the products in parallel?

A: We've kept the one we don't want to implement as the back-up. If we used it we'd need to go back to the start with the regulatory authorities. However we do not expect CHO production to fail at this stage.

Q: Is it still worth getting regulatory approval for the rabbits on a small scale adult trial?

A: We are convinced that the data available shows proof of principle. However we have also concluded that the regulatory bodies would not give approval on the basis of the existing data. The big issue for us is how can we increase the availability of the product. CHO is the fastest way of doing this.

Q: Any information on costs?

A: Need to show treatment works first of all. Have experience of persuading insurance companies/governments to pay for ERT.

Q: Can you give information on trial dates?

A: This is ongoing. Earliest will be early 2001, followed by another 6-9
months later.

Q: Allowing for all obstacles how long till regulatory approval?

A: At least 5 years for all approvals.

No comments:

Post a Comment