A Maintenance Trial in Adults with Gaucher Disease

Gauchers News Contents

Actelion Pharmaceuticals has announced a new trial to assess the safety and effi cacy of miglustat (Zavesca) as a maintenance treatment. The plan is to enrol 50 patients with Gaucher disease in a multi-centre international study which has been approved by the regulatory authorities, writes Prof Tim Cox of the University of Cambridge and Addenbrooke's Hospital.

A new clinical trial has been started to investigate the role of miglustat (Zavesca) in Gaucher disease. Following the publication of the results of the first clinical trial of miglustat in adults with mild-to-moderate disease in 2000,sustained efficacy (effectiveness) was shown in patients, who have been recently untreated or never received enzyme therapy, in 2004. Several confirmatory studies demonstrating the efficacy of this treatment have been published subsequent to the licensing of the drug in Europe and the United States.

Clearly enzyme replacement therapy, which prevents the progressive manifestations of Gaucher disease and ameliorates the anaemia, other haematological abnormalities, enlargement of the liver and spleen - as well as having an influence on the bone symptom, has been the standard of care over the last 15 years or so for this condition; 15 years of therapeutic experience and intensive monitoring based on registries including the ICCG (International Collaborative Gaucher Group) and the study of the responses of validated biomarkers indicate that many of the therapeutic goals of Gaucher disease can be met.

Having established that enzyme replacement therapy reduces many of the effects of the disease in its untreated state, the question arises as to the best means by which therapeutic goals can be met in the long term. At present there is no established definition of disease stability but future targets should ensure that there are no long term complications of the disease and normal wellbeing and quality of life are available for patients with little detectable burden of disease.


The question arises as to whether or not miglustat has a role as a maintenance treatment in adults with Type 1 Gaucher disease once the condition has been controlled with enzyme therapy.

Actelion Pharmaceuticals's new 'maintenance' trial will assess the safety and efficacy of miglustat as a maintenance treatment. This will involve a two year follow-up of patients who meet strict criteria for defining the stability of the disease over the previous two years based on clinical and laboratory parameters.

'This study will be managed by an independent Steering Committee chaired by Dr Atul Mehta in the UK and Dr Derralyn Hughes (UK), Prof Stephan vom Dahl and Prof Claus Niederau (Germany) and Dr David Cutter from Boston, USA.

It is planned that a total of 50 patients will be enrolled from three centres in the USA, one centre in Canada and seven centres throughout Europe. At present regulatory submissions are nearing completion in most countries with approval by appropriate Ethics Committees regionally and internationally.

I was the principal investigator on the first study of miglustat in collaboration with colleagues Dr Carla Hollak (Netherlands), Dr Martin Hrebicek (Czech Republic) and Dr Ari Zimran (Israel) as well as scientists Dr Fran Platt and Dr Terry Butters from Oxford University. I will also be involved in this study with colleagues.

Therapeutic Position

After numerous reports of the use of miglustat in Gaucher disease, there is a need to establish its therapeutic position. Hitherto it has been regarded as a second line treatment for patients unwilling or unable to receive enzyme replacement therapy. The trial has, in my view, been well designed to answer the question as to whether after initial successful treatment for Gaucher disease by enzyme replacement therapy, there is a role for a new means to maintain the disease in stable remission by the use of miglustat.

Miglustat acts by a mechanism that is clearly different from enzyme replacement therapy. By conducting an appropriate programme of clinical research in a multi-national trial we can establish this point - which is of undoubted importance to many patients with Gaucher disease. The proposed trial represents a later stage of development for understanding of the therapeutics of this condition. I consider that the trial, which has passed many rigorous regulatory hoops, is sufficiently powered to address this question.

In my view maintenance therapy in Gaucher disease is a concept that reflects our emerging experience, expectations and perceptions of the life of Gaucher patients in an era in which a life-saving treatment has already been introduced.

'Clearly new trials represent a difficult area for the pharmaceutical companies involved in the commercial aspects of Gaucher disease and for the investigators working within an intensely competitive field of activity which includes newly emerging enzyme therapy and drugs such as miglustat with innovative modes of action.

Ultimately - and provided that the studies are sufficiently powered and well-designed to yield definitive answers to the questions posed - Gaucher patients should benefit. This, of course, depends on the integrity of the investigators, the design of the trial and the effect of the individual drugs available. The investigators will report back to the Association and its readership just as soon as it is possible to do so.

Gauchers News Contents

Source: Gauchers News June 2006.
© Copyright Gauchers Association 2006