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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Sunday, 3 January 2010

Novazyme's results

Before the visit, Randall House and I had to sign confidentiality agreements that meant we couldn't share the evidence we were given. However, I note that the agreement is now out of date, so here it is.

What follows is a series of photographs of tissue from Pompe mice, 3 from a set of 9 we were given, all treated with a stain that shows up glycogen deposits as purple. On the left hand side is tissue from mice treated with the 'standard' alpha-glucosidase (Standard GAA). On the right hand side is the same type of tissue from mice treated with just 2 mg/kg of the Novazyme product (HP GAA) just 6 hours before.


Did you notice what we noticed? That's right - the glycogen in the mice treated with the Novazyme product has completely disappeared. After just 6 hours! And at a dose of only 2mg/kg!

The Novazyme blurb goes on to note that the appearance of the tissue from the mice treated with the standard enzyme was similar to that from untreated Pompe mice, while the tissue from treated with the Novazyme product looked like that from normal mice.

You have to admit that, even now, that looks pretty convincing. Heck, right now, looking at it all, I'm prepared to be convinced all over again.  As I now know from reading The Cure, John Crowley knew exactly how convincing such photos could be, as they made a big impression on him during his visit to Pharming in 1998.

This is the same evidence that, according to The Cure, was shown to Genzyme during the discussions to persuade them to buy out Novazyme.  Which they did - for $137.5 million  (with the promise of $87.5 million more if it worked).   Bearing in mind that Genzyme only paid $20 million for the Synpac product (a real product that had been shown to work) and $17 million to buy into Pharming (ditto) this was a breath-taking sum. A very impressive achievement on John Crowley's part.

And what did Genzyme get for their $137.5 million? Fast forward to November 2003and the IPA Conference held in Heidelberg, Germany. I asked what was happening with the Novazyme product. William Canfield answered. He said that it had not proven possible to replicate the promising results shown with the Novazyme product and that the impressive photographs (above) were simply "an artefact" because  the procedure had been carried out wrongly.  In fact, here is the full question and answer, lifted from the DVD of the conference:

So there you have it. The evidence which had helped persuade Genzyme to part with $137.5 million was "an artefact". A flaw in the process had failed to stain the glycogen still in the tissue samples of the mice treated with the Novazyme product, while staining that in the tissue samples from the mice treated with the other enzyme. In other words, those convincing pictures shown above, which suggested that Novazyme's highly phosphorylted enzyme was superior to the others, were false, because of a "mistake" by Novazyme in conducting the test. Hey, it could happen to anybody.*

The noise of jaws dropping around the room was audible.

There were only 3 possible explanations for this astonishing state of affairs.

1) Novazyme was engaged in an intentional fraud.

I think we can rule out that one. I don't believe that anyone involved was less than sincere and, my own demonstrable gullibility notwithstanding, I see no evidence to suggest otherwise.

2) The Novazyme product was as good as they said, those results were genuine and Genzyme are covering them up.

Again, I don't think so. Apart from anything else, the sheer number of people that would have to have been involved makes it unlikely that it wouldn't have leaked out.  The idea that Genzyme are keeping a genuinely fantastic product in some big hangar like the one at the end of Raiders of the Lost Ark is just plain risible.

3) Novazyme made an incredible, unintentional, undetected mistake and then managed to fool themselves.

We have a winner.  The thing that I had failed to take into account was that if anyone wanted to believe John Crowley more than me, it was John himself.

John Crowley's achievement here was to persuade Genzyme to part with $137 million for a dud. Vaporware. I take my hat off to him, however I think we have to ask - couldn't Genzyme have put all that money to better use? Developing their proven Pompe treatment, say? Just a thought.

In any event, I hope this account scotches any notion that Novazyme had anything to do with the development of a successful treatment for Pompe disease. Clearly, the evidence shows that it did not. Indeed, the existence of Novazyme, in particular the resources Genzyme used to acquire it, may well have delayed the availability of that treatment.

As I said at the start, this is not a story from which anyone comes out well. However, while I hold my hand up and admit that I let my emotions get the better of my judgment regarding Novazyme, at least I didn't blow $137.5 million on it. What were Genzyme thinking? If I was one of their shareholders, I might have some sharp questions to ask.

If you listened carefully in Heidelberg, you could hear the distant sound of Pharming's  Schadenfreude laughter.
*That said, fair play to William Canfield - it probably wasn't his personal mistake and he didn't have to be so honest about it. But he was. The hallmark of a true scientist.

1 comment:

  1. What an incredible history. All those expectations were wrongly raised just because they used the wrong stain? A whole biotech company sailing in the wrong direction just because of this infantile mistake? They did not ask for internal responsabilities to anyone for this?

    As Kevin, I think that this was very probably unintended. I have to think that because John Crowley is the father of 2 Pompe kids and I am confident that their health is the very first priority for him.

    But they had to discover that horrendous mistake at some moment in time? When did this happen? Before or after selling their company to Genzyme? Whathever the answer is, probably Crowley took his decision thinking on what could be the best thing in terms of his project for his children.

    Did all this nonsense history delay the life-saving treatment for desperately ill kids and adults? Probably the big delay came from the wrong decision that Genzyme made about not proceed at all with the transgenic milk project and to focus exclusively on CHO production. However, it is for sure that the Novazyme dissapointment did not help at all, either; and, as Kevin points out, probably diverted very valuable resouces from productive research on Pompe disease. That money went directly into the pockets of very fortunate stock holders. It should not have been that way. In any case, both the Genzyme and Novazyme mistakes surely had a cost in terms of human lifes.

    What happened to Novazyme is incredible, but it is even more incredible the response of Genzyme, which was plainly irrational and not scientifically driven at all. Spending $140 million with no scientific proof behind that decision, with not even a paper published in the scientific literature: It is just incredible. Who buys a house without even demanding to have a look at it? After all this is a Biotech company and science shoud be a very important part of it. The only conclussion that I can drive from this is that biotech companies executives are no different at all from, say, the executives working for a big bank. May be they have a flavour of science, but at the end, sometimes they are just so focused in selling their product that they tend to forget the very nature of the product they are selling, which is a scientific nature. They should have listened to their scientific staff before taking such a nonsense decision.