Pharming/Genzyme issued a press release on 15 March 2000.The link goes to the archived version on the International Pompe Association website.
It noted that after the trial had run for 36 weeks, the 4 babies in the trial were now aged 12 to 17 months. For a disease where infants did not generally live to see the first year, this was in itself remarkable.The press release also spoke of improvements in heart and skeletal muscle. However, there was no actual data. And here was a conflict between scientific integrity and commercial pressures. The Rotterdam team put out their own statement, via Erasmus University, saying that Pharming/Genzyme had been wrong to release the results, as they had not yet been subject to peer review. Notwithstanding the relief with which the press release was received, the Rotterdam team were absolutely correct; the proper place for announcing scientific results is in a journal following peer review. This was particularly true when the results meant so much to desperate families across the globe. It was important to get it right.
A formal publication did follow. Recombinant human alpha-glucosidase from rabbit milk in Pompe patients was published in one of the world's most prestigious medical journals, The Lancet, on 29 July 2000 (Vol 356, pp 397-8). This paper is a real piece of history and, as with the 1991 paper demonstrating that ERT should work in theory, you would be justified in printing it out and putting it on your wall. You can download it from The Lancet's website for free (you will have to register, however this is worth doing as you will then have access to The Lancet's entire searchable archive). Even if you refrain from framing it, please do read it.
In one of life's pleasing coincidences, 29 July is my birthday. I can honestly say that this was the best birthday present that I have ever received and we drank the IPA wine to celebrate.
The paper contained the data and detail missing from the press release, however the overall message remained the same - this was an effective treatment. All children were still alive, all patinets showed progress. The two who had started treatment before the age of 3 months were now out-patients and were breathing without the aid of a respirator. The most prominent effect was on heart size, which had reduced quite dramatically. it was also noted that the required dose was larger than initially thought - during the trial it was increased from 15-20 mg/kg to 40 mg/kg. At this dose, alpha-glucosidase activity was in the normal range for all 4 patients. I've emphasised that because it seemed to confirm that William Canfield's argument at the AMDA conference had been wrong; there was no need to 'bolt on' extra mannose-6-phosphate residues in order to get enzyme activity up to normal levels.
Presciently, the authors added " We recommend that treatment be started early."
The authors were Hannerieke Van den Hout, Arnold J J Reuser, Arnold G Vulto, M Christa B Loonen, Adri Cromme-Dijkhuis, Ans T Van der Ploeg. It was very pleasing to see Christa Loonen included amongst the authors. However this publication represented a particular triumph for Ans van der Ploeg and Arnold Reuser. They had taken enzyme replacement therapy from a lab-based concept to a working treatment making a difference to real children. Decades of work on "a disease no-one has ever heard of" had resulted in some remarkable progress. This was not only the first paper to demonstrate an effective treatment for Pompe disease, it was also one of the first (if not the first) paper showing the efficacy of a transgenic medicine.
Yes, the premature announcement by press release was not ideal. Yes, there were many twists and turns in the road to commercialisation ahead. However, let us pause now in this narrative to reflect on the remarkable progress this small but extremely talented and fiercely dedicated team had made.
At last, a treatment for Pompe disease - and it worked!