Research Update - The Panos Report

Affordable oral iron chelation for all - Date: Thu, 04 Mar 2004 16:45:38 +1100

Dear Friends,

It is a long time since I was actively involved in getting UKTS established in London. Much has happened since then, but our common dream of an effective therapy for thalassaemia still remains to be achieved, while most patients in the world still do not have access even to the minimum standard of acceptable therapy. UKTS played a leading role for many years in the funding of basic research that led to the development of L1, as a cheap oral iron chelator.


For reasons beyond the immediate scope of this message, but still worthy of exploration at a more appropriate time, UKTS and patient representative organisations have subsequently been denied any role in determining the availability and price structure for L1. Furthermore, despite many studies supporting an important role of L1 in oral iron chelation therapy of thalassaemia patients, the protracted dispute between Nancy Olivieri and Apotex continues to create confusion in the minds of many patients, clinicians, ethicisits and regulatory authorities, hindering the development of a wide consensus on the conditions under which L1 may be used to improve iron chelation therapy for thalassaemia.


The limited licensing of L1 in Europe and the recent rejection of the case of Dr Olivieri by the European Court are important steps forward, but they do not seem to have daunted Dr Olivieri in her dispute with Apotex over L1. We would be all be clapping in favour of Dr Olivieri if her dispute with Apotex was focused on safeguarding patients' interests and research integrity against interference by big pharma.
Unfortunately, the dispute has reached the stage where patients interests are being abused and harmed in the name of safeguarding "research integrity". I have copied to some of you in the past my correspondence urging Dr Olivieri to make a public reassessment of L1, not only on the basis of her initial observations that led her to suspect lack of efficacy and increased risk of liver fibrosis, but also taking into account all the other studies that have been published since then.


Unfortunately she has failed to respond directly to my messages.
Furthermore, in a public statement released last month, she raised new claims that several "premature deaths" of patients have occurred since the licensing of deferiprone in Europe. These new claims, in a non-scientific circular, contrast with the increasing evidence from a number of respected groups in peer-reviewed scientific journals, that have failed to find any evidence of increased risk of liver fibrosis and support a valuable role of L1 in reducing intracellular iron damage, the most likely mechanism of continuing iron damage in patients that are well chelated with desferal. I have therefore taken the initiative to ask Dr Olivieri to clarify the basis for her new claims. Again she has failed up to now to respond directly to my messages.


However, Prof David Nathan has responded on her behalf, proposing that the claimed "premature deaths" have happened among patients "after a short time on L1". Were it not for the respect that we all have for Prof David Nathan, I would have said that this is the most un-scientific statement I have ever heard in my life. That Prof Olivieri and Prof Nathan can make such claims after 15 years of clinical studies on L1 and when thousands of patients are currently receiving L1 without a single scientific report of "premature deaths" indicates to me that the "murky story of deferiprone", as has been recently called by Prof Savulescu, is far from over.


The only clear beneficiary out of this "murky" story up to now has been Novartis who has fully exploited the situation to expand its desferal monotherapy into more and more markets at exhorbitant prices and is now "rolling out" its long-heralded oral iron chelator, without providing the slightest evidence that it canprotect against intracellular oxidative damage, in the way L1 does.


Besides the general obligations that UKTS shares with TIF and national patient support groups in other countries towards thalassaemia patients, UKTS also has the moral authority and justification to ASSERT a key role in resolving the continuing dispute over the use of L1 and DEMAND a voice in determining the price structure for L1 in various countries in favour of patients.


The early development of L1 was funded exclusively by UKTS, so it is immoral and unethical for Apotex or any other drug company to claim a unique right in determining the price structure of L1.


UKTS can speak and demand a saying on these issues with the moral authority that comes out of its role in the early development of L1, as well as on behalf of all the thalassaemia patients that are participating selflessly in clinical trials, often at considerable risk and great discomfort to themselves.


TIF and other national patient organisations have of course a role in this as well. As a first step in this direction, I therefore propose for UKTS to establish a comprehensive web page on "Iron Chelation".

This should include sections containing:

a) Key documents (grant applications, reports & correspondence) demonstrating the role of UKTS in the early development of L1 and documenting its new role to get drug companies to make iron chelators available to thalassaemia patients at affordable prices in all countries;

b) Key scientific publications on iron chelation therapy (with permission from scientific journals, where necessary);

c) Key documents relating to the Olivieri/Apotex and Olivieri/European Court cases;

d) Information on new iron chelators at various stages of development;

e) A professional forum for publishing correspondence and open discussion on oral iron chelators;

f) A patient forum to provide authoritative guidelines and information to patients in various countries on the use of oral iron chelators.

Oral iron chelation is a job half-complete. While we all hope that even more efficient and safer oral iron chelators than L1 may still be developed, UKTS should take again a leading role on oral iron chelation, as it is demanded by the new circumstances. I am sure that an initiative to make desferal and oral iron chelators available at affordable prices to thalassaemia patients in all countries will be greatly applauded by the medical and scientific communities and patients all over the world.
As always dedicated to the struggle for the effective therapy of thalassaemia,

Yours sincerely,

Panos Ioannou,PhD Head, Cell & Gene Therapy (CAGT) Research Group The Murdoch Childrens Research Institute,
Royal Children's Hospital Flemington Road,
Parkville 3052, Melbourne, Australia

Associate Professor, Dept of Paediatrics, University of Melbourne Honorary Senior Scientist, The Cyprus Institute of Neurology & Genetics