IHS Global Insight Perspective | |
Significance | The National Institute for Health and Clinical Excellence has published preliminary guidance recommending the use of Alzheimer's drugs Aricept, Reminyl, and Exelon for the treatment of mild-to-moderate Alzheimer's disease (AD), and Ebixa for the treatment of moderate or severe AD. |
Implications | Aricept, Reminyl, and Exelon are already recommended as treatment options for moderately severe AD, and this latest appraisal will see the drug extended for use in earlier stages of the disease. Ebixa will also be made available on the National Health Service, albeit in a more restricted setting. |
Outlook | With up to 380,000 people suffering from AD in England and Wales, the impact of this guidance is expected to be significant. |
The U.K. National Institute for Health and Clinical Excellence (NICE) has recommended lifting restrictions on the use of Alzheimer's disease (AD) drugs Aricept (donepezil; Eisai/Pfizer, Japan/U.S), Reminyl (galantamine; Shire Pharmaceuticals, U.K.), Exelon (rivastigmine; Novartis, Switzerland), and Ebixa (memantine; Lundbeck, Denmark) in the National Health Service (NHS). This decision follows a review of prior guidance issued in November 2006 and June 2009. The cost watchdog has today issued a new appraisal consultation document (ACD), which states that acetylcholinesterase (AChE) inhibitors Aricept, Reminyl, and Exelon are recommended for the treatment of mild-to-moderate AD, subject to several conditions:
- Treatment can only be initiated by a specialist.
- Treatment should only be continued in patients in whom there is a positive effect on cognitive, global, functional, and behavioural symptoms.
- A progress review should be conducted every six months based on cognitive, global, functional, and behavioural assessment by a specialist team.
- The lowest cost AChE inhibitor should always be prescribed first. However, patients are permitted to switch to another drug if adverse events arise or if there are issues relating to dosing, drug interactions, adherence, or medical comorbidity arises.
NICE has also recommended the use of Ebixa for the treatment of moderate or severe AD in patients who are intolerant of or have a contraindication to AChE inhibitors, provided that the same conditions attached to the use of the AChE inhibitors (with the exception of the fourth condition) are met.
In its review of the cost effectiveness of the drugs, NICE's assessment group did a systematic review of all published economic evaluations of the drugs since 2004. Eisai and Lundbeck also provided new economic analysis for their respective drugs.
AChE Inhibitors
The assessment group's review of eight studies on the cost effectiveness of Aricept supported the use of the drug. Meanwhile, the manufacturer's new analysis showed that when compared with best supportive care (BSC), Aricept dominated BSC in terms of being cheaper yet more effective, with overall cost savings of £2,354 (US$3,750) and an estimated delay to institutionalisation of two months. The manufacturers of Reminyl and Exelon did not submit any new data, so the analysis was based on the assessment group's review of four studies on the cost effectiveness of the drugs. The general consensus was that these studies supported the cost effectiveness of the two drugs. In terms of measuring the relative cost effectiveness of the three AChE inhibitors, NICE said that there was not enough evidence to facilitate the analysis.
Ebixa
Looking at the cost effectiveness of Ebixa for the treatment of moderate-to-severe AD, the new economic model submitted by the manufacturer compared Ebixa with BSC. Ebixa dominated BSC and was associated with savings of £1,711. The assessment group also developed a separate model that showed that the incremental cost-effectiveness ratio of Ebixa was £32,100 per quality adjusted life year. The difference in results was attributed to the fact that the model used different values for the delay to full-time care; the manufacturer's model did not assume that treatments continued following institutionalisation, whereas the assessment group's model accounted for this. NICE concluded that Ebixa should only be recommended in cases of intolerance or contraindication to AChE inhibitors. The ACD is available here.
The Four AD Drugs at a Glance | |||
Drug | Manufacturer | U.K. Indication | Annual Cost of Treatment |
Aricept | Eisai/Pfizer | The symptomatic treatment of mild-to-moderately severe Alzheimer's dementia. | The cost of tablets is £63.54 (5 mg, 28-tablet pack) and £89.06 (10 mg, 28-tablet pack). The cost of orodispersible tablets is £63.54 (5 mg, 28-tablet pack) and £89.06 (10 mg, 28-tablet pack). |
Reminyl | Shire | The symptomatic treatment of mild-to-moderately severe dementia of the Alzheimer's type. | The cost of tablets is £68.32 (8 mg, 56-tablet pack) and £84.00 (12 mg, 56-tablet pack). The cost of the oral solution form is £120.00 (4 mg/ml, 100 ml). The cost of capsules is £51.88 (8 mg, 28-capsule pack), £64.90 (16 mg, 28-capsule pack), and £79.80 (24 mg, 28-capsule pack). |
Exelon | Novartis | The symptomatic treatment of mild-to-moderately severe Alzheimer's dementia. | The cost of 1.5 mg, 3 mg, 4.5 mg and 6 mg rivastigmine capsules is £33.25 (28-capsule pack) and £66.51 (56-capsule pack). |
Ebixa | Lundbeck | The treatment of patients with moderate-to-severe Alzheimer's disease. | The cost of memantine tablets is £34.50 (10 mg, 28-tablet pack), £69.01 (10 mg, 56-tablet pack), £138.01 (10 mg, 112-tablet pack), and £69.01 (20 mg, 28-tablet pack). |
Source: NICE |
Outlook and Implications
This positive preliminary guidance has been applauded by the manufacturers, patients, and advocacy groups alike, who have for a long time campaigned for the drugs to be provided in the current appraised indications. NICE's initial decision not to recommend the reimbursement of AChE inhibitors in early stage AD and Ebixa in moderate-to-severe AD was denounced by patient groups, and a legal challenge was mounted by the pharmaceutical companies and patient groups. NICE went on to review the decision in 2009, but maintained its initial verdict that the drugs were not cost effective (see United Kingdom: 11 June 2009: NICE Maintains Prior Recommendations on Alzheimer's Drugs Aricept, Reminyl, Exelon, Ebixa).
According to the chief executive of NICE, Andrew Dillon, this spectacular u-turn is driven by data from new clinical trials that support the efficacy of the drugs. Furthermore, he added that there is now more information available on the full costs of treating the various stages of the disease. NICE estimates that there are about 380,000 people suffering from AD in England and Wales. Between 50% and 64% of AD patients are estimated to have mild-to-moderately severe disease, and approximately 50% of AD patients are estimated to have moderately severe-to-severe Alzheimer's disease. This preliminary guidance is therefore expected to have a major impact on the treatment of the disease in the United Kingdom. A second appraisal meeting is scheduled for 25 November, after which a final appraisal determination will be issued.