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.

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Monday, 21 December 2009

1999 - The Year of the Rabbit!

In one of life's pleasing coincidences, 1999 was the Year of the Rabbit in the Chinese calendar. There was, of course, continued strong interest in the ERT trials and eventually the Genzyme/Pharming partnership agreed to answer patients' questions with a Q & A, released to the AMDA, AGSD-UK and VSN and posted to GSDNet (22 February):

Questions and Answers

1. Have the clinical trials started?

Approval for a small pilot study on 4 infants and 3 juvenile patients was
recently received in the Netherlands. The study has begun at the Sophia
Children's Hospital in Rotterdam and inclusion of patients has started. Dr.
Ans van der Ploeg is the principal investigator. This study is designed to
assess safety and give indications of efficacy of recombinant human
alpha-glucosidase in this population.

If successful, data obtained while the pilot trial is in progress will be
used to design two larger Phase II/III trials in the US and Europe.
Detailed design of these trials can only be done when data from the pilot
trial are available. Our goal is to initiate the first of these 2 studies
in mid-1999.

2. How can I participate in upcoming additional clinical trials?

Once the protocol and sites have been established, your physician should
contact the principal investigator at the participating center to determine
whether a patient can participate. Your physician should also inform you
about the consequences of trial participation, such as potential side
effects, additional examinations, prolonged hospital stay and costs.

3. How are patients selected for these clinical trials?

Before starting clinical trials, the principal investigators and
participating institutions will be identified. The investigators will
follow a predefined protocol with patient inclusion and exclusion criteria
that define patient eligibility for trial participation, as well as the
number of patients that can be enrolled. Inclusion or exclusion is
determined by a selection committee consisting of several physicians
including the primary investigator(s) based on the protocol.

4. What are the inclusion/exclusion criteria for the trials?

The protocols for the Phase II/III clinical trials have not been determined
to date as they will be dependent on the results of the Phase II pilot
trial in the Netherlands.

5. Who are the principal investigators and institutions in the next trials?

The participating physicians and institutions have not been determined yet.
Your local patient organization (AMDA in the U.S., AGSD in UK, VSN in
the Netherlands) will be informed on all progress toward trial preparation.

6. How will patients from other countries be able to participate in
clinical trials performed in the US and/or Europe?

Your physician should contact the principal investigator(s) at the
participating center(s) to understand the inclusion and exclusion criteria
for the protocol, and to determine whether a patient might be eligible for

7. What are the starting dates for the trials?

The initial, small pilot study taking place in Rotterdam has begun. Our
goal is to implement the next trial in mid-to-late 1999.
8. Will therapy be continued for trial patients after completion?

If the product proves efficacious in the trial, our plan is to continue
patient treatment under the Pharming/Genzyme LLC until regulatory approval
has been obtained.

9. Is it possible to start treatment for patients concurrently with or
after completion of the clinical trial?

Construction of a large scale production plant is underway in Belgium.
Until that time, product supply is available from a small pilot plant to
support the limited patients that are enrolled in the Phase II/III clinical
trials. The large scale production plant is scheduled to be operational
around mid-2000. Within the framework set by international legislation and
the limits to product supply, the Pharming/Genzyme LLC joint venture will
evaluate the possibilities for patient treatment concurrently or after
completion of the clinical trial.

10. Has the FDA already given the go-ahead in start clinical trials in the

Not at this time. Pharming/Genzyme LLC is working to complete the
application to perform the clinical trials in the US (i.e.. the IND,
Investigational New Drug Application). The FDA will allow us to start
clinical trials only after we have finalized the clinical protocol and
submitted it to them for review. In Europe, the required approvals to
perform clinical trials must also be obtained.

11. When will the product be approved?

The Pharming/Genzyme LLC is committed to working diligently and thoroughly
to develop a safe, efficacious product as quickly as possible. As always,
timelines may shift depending upon the outcome of the trials, review time
by the FDA in the 'US and the EMEA in Europe, and production capacity at
our manufacturing facilities.

After successful completion of the Phase II/III clinical trials in infants,
the Pharming/Genzyme joint venture will apply for product approval for this
population. Completion of this clinical trial, assessment of results,
filing of the application and review by the FDA may take as long as 12-24
months. In Europe, we must complete a Market Authorization Application with
the EMEA, the central European regulatory body, to obtain approval in the
member states of the European Union.

A second trial in juvenile patients is planned to start later, and the
trial will most likely take longer to complete. Thus, the process until
approval for treatment of juvenile patients may take until mid-to-late

This document contains forward-looking statements about the anticipated
initiation of clinical trials, the expected continuation of patient
treatments, the adequacy of the capacity of the small pilot scale plant for
clinical trials and of the large scale production plant, the expected time
the large scale production plant will become operational, the estimated
time required for conducting development and regulatory approval
activities, and the estimated size of the Pompe disease patient population.
Actual results may differ materially depending on the actual timing and
results of clinical trials, the timing of regulatory submissions, the
content and timing of decisions of the FDA and other regulatory agencies
concerning products and manufacturing facilities, actual amounts of product
needed for clinical trials and commercialization activities, the rate of
enrollment of patients in clinical trials, the continued funding of the
joint venture, and the adequacy of the companies' information about the
Pompe disease patient population. (Pharming/Genzyme LLC--February 1999)
Apologies for this cut and paste job, however it is not (just) laziness on my part. This is an important historical document and therefore worth quoting in its entirety.

A few things to note.

1) This confirmed for the first time that the trials were actually underway i.e. that actual Pompe patients were receiving the enzyme (and had been for a while).

2) While this was exciting, it was also a disappointment to many - there was no mention of a trial for adults, for example. 

A short statement from Synpac  indicated that they too expected to start clinical trials, in conjunction with Y T Chen, by the middle of 1999.

So, we now knew that trials had started and what the plan was for future development. We had to  hold our breaths and hope that it worked.  In the meantime, the nascent International Pompe Association began to grow and the date of the first conference was fixed for 2-3 July, 1999, in Naarden, the Netherlands.

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