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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Saturday, 2 January 2010

Things get complicated

Out of the blue, on 19 April 200, came a press release from Genzyme, announcing that they were buying the rights to the Synpac product. under the deal it seemed that Genzyme paid $20 million to Synpac and Pharming paid $10 million to Genzyme. It looked like the Genzyme/Pharming joint venture would now commercialise ERT using the Synpac product ie one produced in fermenter vessels using chinese hamster ovary (CHO) cells.

What on earth was going on? What would happen to patients already receiving the rabbit enzyme? Why was this happening? Was the Synpac enzyme better?

Rumours abounded. The Duke/Synpac trial results had not yet been published however it was put about that the results (based on 3 patients) were better than those for the Rotterdam trial. As it turned out, this was not the case. However it ushered in a period of great uncertainty for patients.

It is true that enzyme production in rabbit milk was more difficult than originally anticipated. The rabbits did not produce as much enzyme as hoped and the Rotterdam trial showed that more enzyme was needed than originally thought too. The initial estimate that one rabbit would produce enough for one patient was now looking very optimistic indeed. However, they could be seen as a stop-gap until a larger milk producer - cows - could be brought on-stream. That did not seem to be in the game plan though.

And while all the above may have been true (though not necessarily the show-stopper it was all purported to be) it is certainly true that the move to CHO production suited Genzyme. They had a track record of enzyme production by that method and manufacturing-scale facilities already in use for their Gaucher product. This turn of events locked Pharming into the CHO method for the joint project with Genzyme. As the path to commercialisation became longer, the drain on Pharming's resources became too much for the small company and they went into receivership on 10 August 2001 . A potential long-term competitor to Genzyme was removed; Pharming slept with the fishes (as far as the Pompe project went anyway - they survived receivership and are still a going concern).

Of course, I am in no way suggesting that this is an outcome that Genzyme were actively working towards - it's just the way things turned out.

There was certainly no lack of commitment to the success of the joint venture, as evidenced by the recruitment of Paul Kaplan, who had a 10-year record in drug development, to lead it into the next phase.

I'm getting ahead of myself there though. All this was still to unfold. For now (and for the next few years) the IPA was involved in a battle to ensure that those on the Pharming trial continued to receive the Pharming enzyme, on which they were doing demonstrably well.

It was unsettling - things just didn't seem to be progressing to the timescale that patients would have liked. There was a suspicion that this might be due to the lack of competition.

Then, all of a sudden, there was competition again - in the form of Novazyme, a new company headed by John Crowley.

The notes of IPA meetings at the time show that

1 comment:

  1. After reading all these posts I can only think that Genzyme made some very serious mistakes and erroneous decisions at the very critical moments. I feel that my son Lucas has been one of the unintended victims of these mistakes, as otherwise there is a possibility that ERT might have been already available at the moment of his birth, on february 2002. Now he is in a wheelchair and totally dependent on his ventilator.

    Of course those error were unintended; but I think that is important to remember them, in order to avoid repeating them in the future. From my point of view, a few questions arise from that experience:

    1 - Why was the rabbit milk project completely stoped when in proved to be successful from the clinical point of view? I think that Genzyme did not give enough weight to the fact that this was a life saving treatment and did not take into account the sense of urgency that is related to patients who are desperately ill. Of course logistic and product development issues are very important in the long run, but the rabbit milk alternative should have kept in, even if it a much smaller scale than initially planned, to keep on with the necessities of the most desesperately ill patients in the short run. The history of Pompe disease prove that patients organizations were one of the key actors, and their most important necessities should have been taken into account by the biotech industry in those critical moments. I have the sensation that they did not listen hard enough to the patient needs at those key moments.

    2- Was it was a wise decision to put all the eggs in the same basket when you had to different alternatives to developed? The years that have passed since then have proved that it was not. Genzyme has faced much more problems than they expected in developing and manufacturing the CHO product, particularly in the US. As a matter of fact they are still facing them today! It would have been a very wise decision to keep some rabbit milk producing facilities running to help to cope with those difficulties. Going exclusively through the CHO option was a grave mistake. Why should you ride only in one highway, when the state of that highway is still uncertain when you have the possibility of using two different ones?

    3- Will a corporation as Genzyme learnt about the mistakes of the pasts? I am pessimistic about those issues. I think that this type of mistake is the consequence of the very way in which big corporations work. You might have the right people working at the right place, but you cannot take for granted that someone will not take a very irrational decision at a very key moment. Even if we are talking biotech here, those are profit driven decisions, and sometimes the need to make a good business prevails over purely scientific an rational criteria. If that is the case, I think that the results would rarely be good. The purchase of Novazyme is a very good example of that, as it only delayed more the process of product development and, besides, from the scientific standards, and even from the crematistic criteria, was pure nonesense. My main bitterness about this, is that I think that these type of mistake could be repeated in the future, even when it comes to Pompe disease. Not by the people who made them, of course, but by the people who will be substituing them in the next 10 or 20 years. It is a sure thing that they will end up forgeting this history. That is why it is some important the effort is making Kevin in writing this history, even if most doctors and biotech executive might surely have little interest in reading the amazing history of this minoritary disease.