Prometax: Withdrawal of the application to change the marketing authorisation

Exelon and Prometax are medicines that contain the active substance rivastigmine. They are available as capsules, oral solution and transdermal patches (patches that deliver the medicine through the skin) of various strengths.

Exelon and Prometax have been authorised in the European Union since May 1998. All forms of these medicines can be used for the treatment of patients with mild to moderately severe Alzheimer's dementia, a progressive brain disorder that gradually affects memory, intellectual ability and behaviour.

The capsules and oral solution can also be used to treat mild to moderately severe dementia in patients with Parkinson's disease.

The 13.3 mg/24h transdermal patches of Exelon and Prometax were also expected to be used to treat patients with severe Alzheimer's dementia.

The transdermal patches of Exelon and Prometax are expected to work in patients with severe Alzheimer's dementia in the same way as they work in patients with mild to moderate Alzheimer's dementia.

In patients with Alzheimer's dementia, certain nerve cells die in the brain, resulting in low levels of the neurotransmitter acetylcholine (a substance that allows nerve cells to communicate with each other). The active substance in Exelon and Prometax, rivastigmine, works by blocking the enzymes that break down acetylcholine: acetylcholinesterase and butyrylcholinesterase. By blocking these enzymes, rivastigmine allows levels of acetylcholine to be increased in the brain, helping to reduce the symptoms of Alzheimer's dementia.

The company presented the results of a 24-week main study involving 716 patients with moderately severe to severe Alzheimer's dementia, which compared the 13.3 mg/24h transdermal patch with a non-effective lower-dose, 4.6 mg/24h transdermal patch. The medicine was compared with a lower-dose patch rather than placebo (a dummy treatment) in this study because of previous experience of the company showing patients on placebo failing to complete their treatment. The main measures of effectiveness were changes in symptoms in two main areas: cognitive (the ability to think, learn and remember) and global (a combination of several areas including general function, cognitive symptoms, behaviour and the ability to carry out everyday activities).

The application was withdrawn after the CHMP had evaluated the documentation provided by the company and formulated lists of questions. After the CHMP had assessed the company's responses to the questions, there were still some unresolved issues.

Based on the review of the data and the company's response to the CHMP lists of questions, at the time of the withdrawal the CHMP had some concerns and was of the provisional opinion that the 13.3 mg/24h transdermal patch could not have been approved for the treatment of patients with severe Alzheimer's dementia. Although the 13.3 mg/24h transdermal patch had a greater effect on symptoms than the non-effective lower-dose patch, the CHMP was not convinced that this effect would translate into a clinically meaningful benefit, particularly for those patients with the most severe form of Alzheimer's dementia. In addition, even though the safety profile of the patch in patients with severe Alzheimer's dementia was similar to that in patients with mild to moderately severe Alzheimer's dementia, the CHMP was concerned that several side effects (including falls, vomiting and diarrhoea, dehydration, loss of appetite and psychiatric disorders) seemed to be more common and more severe in patients with severe Alzheimer's dementia. This could have more serious consequences in patients with severe disease, which is of concern in this more vulnerable population.

Therefore, at the time of the withdrawal, the CHMP was of the opinion that the benefits of Exelon/Prometax transdermal patch in the treatment of patients with severe Alzheimer's dementia did not outweigh its risks.

In its official letter, the company stated that its decision to withdraw the application was based on the CHMP's view that the data provided in support of the new indication are not sufficient to recommend approval.

The letter from the company notifying the Agency of the withdrawal of the application is available here.

The company informed the CHMP that there are no consequences for patients currently included in clinical trials with Exelon or Prometax.

If you are in a clinical trial and need more information about your treatment, contact the doctor who is giving it to you.

There are no consequences for the use of Exelon and Prometax in their authorised indications.