NICE Clears Botox For Chronic Migraine, With Therapy “Stopping Rules”

With rules in place about when to stop therapy, the U.K.'s National Institute for Health and Clinical Excellence clears Allergan's botulinum toxin, Botox for use as prophylaxis in patients with chronic migraine and who have tried other therapies.

Although it had doubts initially, the U.K.'s cost watchdog, the National Institute for Health and Clinical Excellence (NICE), has cleared Allergan Inc.'s Botox (onabotulinumtoxinA) for use in the National Health Service for prevention of chronic migraine in patients who have not responded to at least three prior preventative treatments and whose condition is not caused by the overuse of medication.

The final guidance on the additional indication for the botulinum toxin type A therapy, issued June 27, shows that cost was not the central issue in an earlier proposal to reject coverage: Allergan will not have to offer a patient access scheme or discount Botox's price. The final guidance also confirms a final appraisal determination, released in May, which also recommended the use of Botox in chronic migraine.

Allergan said the positive decision from NICE was partly due to the hard work of the U.K.'s headache and migraine community, which submitted substantial commentary to NICE after the institute said it was thinking of rejecting the drug, outlining the debilitating nature of chronic migraine and the potential role of Botox as an option to manage the condition.

In chronic migraine, Botox is injected into 21 to 39 sites around the head and the back of the neck, repeated every 12 weeks. A 200-unit vial of Botox costs £276.40 ($430) in the U.K., and with the cost of administration estimated at £73 per treatment, the total cost of therapy works out at £349.40 for each treatment course.

Draft Called For Further Analysis

In draft guidance issued Feb. 16, 2012, NICE's appraisal committee was concerned that the well-known muscle-paralysis effect of Botox meant that patients in placebo-controlled trials knew which arm of the clinical trial they were in. They also thought the amount of clinical benefit obtained from Botox was small and its long-term effects uncertain. It asked Allergan for further information and analyses, even before any cost-effectiveness calculations were made.

The company later submitted a revised economic model, which has addressed the appraisal committee's concerns, and was associated with the "most plausible" incremental cost effectiveness ratio of £18,900 per QALY gained, according to NICE. This is well below the cut-off for a NICE positive appraisal of around £20,000 to £30,000, the institute noted.

The revised model incorporated stopping rules – guidance on when Botox prophylaxis should be halted. These rules included stopping prophylaxis when a patient's condition is not adequately responding to treatment, defined as less than 30% reduction in headache days per month after two treatment cycles. Botox should also be stopped when a patient's condition changes to episodic migraine, defined as fewer than 15 headache days per month for three consecutive months.

The appraisal committee pooled data from two randomized control trials, PREEMPT 1 and 2, which showed that Botox was associated with a significant reduction of 8.4 headache days per month, from 19.9 days at baseline, compared with a reduction of 6.6 headache days per month from a baseline of 19.8 days in the pooled placebo group.

Patient advocacy groups welcomed the final guidance, saying that Botox was the one of the few options for patients debilitated by chronic migraine. It was potentially a life-changing treatment – chronic sufferers are often unable to work and struggle to meet household and family responsibilities, the groups said. Current options for chronic migraine include triptans, tricyclic antidepressants, beta-blockers and anti-epileptics, although the market is expected to grow with newer therapies like Botox (Also see "Migraine Snapshot: Despite Significant Generic Presence, MAP, Allergan, Others See Big Market Potential" - Pink Sheet, 28 May, 2012.).

Allergan estimates around 730,000 adults have chronic migraine in the U.K., although only around one-fifth are properly diagnosed. And around a third of diagnosed patients already have tried three or more preventative therapies, so are eligible for Botox treatment.

Zytiga And Tarceva Cleared

NICE also released on the same day final guidance recommending Johnson & Johnson's Zytiga (abiraterone) as an option in the treatment of castration-resistant prostate cancer that has progressed on or after one docetaxel-containing therapy; the FAD recommended approval in May after the company submitted a patient access scheme and extra analyses (Also see "NICE Price: Zytiga On Track In England After Discount" - Pink Sheet, 17 May, 2012.).

NICE also recommended the use of Roche's Tarceva (erlotinib) as an option in patients with locally advanced or metastatic EGFR-mutation positive non-small cell lung cancer, following the submission of a patient access scheme. NICE had initially said it wouldn't recommend erlotinib's use in this setting (Also see "NICE Doubtful On Cost-Effectiveness Of Tarceva" - Pink Sheet, 17 Feb, 2012.).

However, NICE confirmed that it had rejected the use of GlaxoSmithKline PLC's lapatinib (Tyverb) or Roche's Herceptin (trastuzumab) for use with aromatase inhibitors in the treatment of patients with metastatic breast cancer. The extent to which the drugs improved overall survival when used with letrozole or anastrozole was small or difficult to quantify, NICE's appraisal committee concluded. NICE first said it would turn down the two drugs in December 2010 .