The final appraisal determination (FAD) from the UK’s National Institute for Health and Clinical Excellence (NICE), issued on Friday, makes no concession to its earlier ruling that patients newly diagnosed with mild Alzheimer's disease are not to be allowed access to drugs on the National Health Service.
This is at variance with the recommendation in March from the Scottish Intercollegiate Guidelines Network (SIGN), backing the use of cholinesterase inhibitors for the treatment of people at all stages of Alzheimer’s.
Cholinesterase inhibitors boost levels of acetylcholine, a messenger chemical that communicates between nerve cells, and that becomes deficient in the Alzheimer brain.
The latest NICE statement actually represents a movement forward from its stance in 2005, when it rejected outright all mild-to-moderate drug treatments, to be followed by a modification earlier this year which permitted treatments for moderate cases under its first appraisal consultation document.
But for how long can NICE hold out against new clinical evidence suggesting that earlier diagnosis of AD could help sufferers stay more like their own selves - the mantra behind the ads for Aricept (donepezil - from Eisai/Pfizer) that are appearing on American TV?
Companies have three weeks to appeal against the statement, and Eisai promptly issued a press release saying that it would challenge the decision.
Dr Paul Hooper, managing director of Eisai, said: “What NICE are proposing is perverse. Their own draft guidelines call for earlier intervention in dementia, yet they seek to withhold the only treatments which has been shown to hold back the progression of this devastating condition.”
Meanwhile, according to Dr Daniel Kaufer of the University of North Carolina School of Medicine, the USA is facing a NICE-style problem. “Dementia trials are being done in very artificial circumstances ... The real challenge lies with optimising treatment for the mild-to-moderate individual with AD.”
His own work has focused on the value of Shire’s prolonged-release Reminyl XL (galantamine) cholinesterase inhibitor, a once-a-day formulation sold as Razadyne in the US by Johnson & Johnson. A key finding has been its beneficial circadian rhythm effects. Lowered levels at night, which follow acetylcholine's natural pattern in the body, have produced no sleep disorders, as compared with the 10% of patients on Aricept who suffer insomnia, of whom 6% have nightmares.
Acetylcholine, he explains, is generally good. “It's one of the great deficits in AD. But too much at night is not good.”
Shire markets the immediate-release Reminyl and Reminyl XL in the UK, where they are licensed for the treatment of mild and moderate dementia of the Alzheimer’s type. The company said in a statement it was "considering all options following the issue of this FAD, including the option to appeal.”
Ebixa also affected
Meanwhile, Danish drugmaker Lundbeck said in a statement that the FAD effectively means that its Ebixa (memantine) drug, the only licensed treatment for patients with moderate to severe Alzheimer's disease, will no longer be available on the NHS in England and Wales.
The company said that denying patients the right to receive Ebixa, which works by blocking N-methyl-D-aspartate receptors, means that there is now no option fo the 50% of Alzheimer's patients who cannot be treated with cholinesterase inhibitors.
"Lundbeck believes the position of NICE discriminates against one of the most vulnerable patient groups, those with advanced Alzheimer’s disease, for whom no other licensed treatment exists," it said.