The clinical effectiveness agency for England and Wales says that it will reverse its highly unpopular decision to deny three medications to people with mild Alzheimer’s disease, and a fourth to people with moderate to severe disease.

The National Institute for Health and Clinical Excellence said Oct. 7 in draft guidance on four Alzheimer’s drugs that rivastigmine (Exelon, Novartis), donepezil (Aricept, Eisai/Pfizer) and galantamine (Reminyl, Shire) would now be recommended to the National Health Service for their full licensed indications, which include the treatment of people with mild disease. Existing NICE guidance on Alzheimer’s, first issued in 2006 and updated most recently in 2009, recommends the three drugs, known as acetylcholinesterase (AChE) inhibitors, for the treatment only of moderate disease, leaving clinicians with few options but to wait for patients to deteriorate before starting treatment.

Also in the current draft guidance, memantine (Ebixa, Lundbeck), a drug for more severe disease, is recommended only in the context of clinical studies in England and Wales.

The Alzheimer’s guidance was from the outset deeply unpopular among physicians, patient advocates, and the drugs’ manufacturers; it did, however, survive a legal challenge in 2006, led by the firms that developed and marketed donepezil, Eisai and Pfizer. The two companies had charged NICE with “irrational” decision-making, discriminatory practices, and procedural breaches in the presentation of its economic models.

NICE’s reviewers, in draft documents released Oct. 7, said that they had reviewed evidence from 17 randomized controlled trials published since the current guidance was created, along with several systematic reviews. While NICE criticized the design and quality of evidence generated by some of the trials, the pooled evidence for the AChE inhibitors did improve the drugs’ efficacy picture for people with mild to moderate disease, they said, at least in terms of cognitive outcomes.

NICE also re-examined its cost-effectiveness analyses in light of the new data, citing in a press statement “new clinical trials that support and strengthen findings about the effectiveness of AChE inhibitors in mild as well as moderate disease; greater confidence in the impact of these drugs on the balance of time spent before and after needing to live in a residential or nursing home, and more clarity about the impact of these drugs on the costs and health outcomes associated with having Alzheimer’s disease over time as the illness becomes worse.” The agency did not provide incremental cost-effectiveness ratios for any of the AChE inhibitors.

Donepezil, at 5 or 10 mg daily, costs £63.54 for a 28-day pack of 5 mg tablets and £89.06 for 10 mg. Galantamine, at 8 or 12 mg twice daily, costs £68.32 or £84.00 per 56-tab pack. Rivastigmine, usually 3 or 6 mg twice daily, costs £66.51 for a 56-tab pack at 3 mg and the same at the 6 mg dose.

Memantine, taken once daily, is priced at £34.50 for a 28-tab pack at 10 mg; daily doses may vary from 5 to 20 mg.

NICE estimated memantine’s cost-effectiveness ratio at less than £32,100 per quality of life-adjusted year gained for people with moderate to severe Alzheimer’s disease, and less than £26,500 per QALY gained for patients with severe disease.

Severity of Alzheimer’s disease is measured by NICE using the Mini Mental State Examination (MMSE) score of cognitive impairment. Mild Alzheimer’s disease carries an MMSE score of 21–26; moderate of 10–20; moderately severe of 10–14; and severe Alzheimer’s disease of less than 10. NICE estimates that 380,000 people in England and Wales have Alzheimer’s, and of these more than half have mild to moderate disease, with the rest having more severe disease.

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