Pradaxa Almost Clear Of NICE Hurdle

Boehringer Ingelheim has answered all of NICE's questions on Pradaxa, meaning it is on the brink of being used in the NHS.

Boehringer Ingelheim GmbH's nod from England's National Institute for Clinical Excellence for use of its oral anticoagulation drug Pradaxa (dabigatran) for its licensed indication gives the company a slight head start over rivals, including Bayer AG/Johnson & Johnson's Xarelto (rivaroxaban) and the potentially even more clinically attractive Pfizer Inc./Bristol-Myers Squibb Co.'s apixaban.

NICE's decision covers the scope of Pradaxa's approval for prevention of stroke and systemic embolism in people with nonvalvular atrial fibrillation. Xarelto was cleared for AFib by the European Medicines Agency on Sept 22, 2011 - though this has yet to be confirmed by the European Commission - and approval for apixaban in this indication is expected to be a few months away.

Though it comes as no real surprise, the decision in NICE's final appraisal determination all but rubber stamps the inclusion of the drug in the NHS, which was previously delayed due to NICE's concern over potentially biased cost-effectiveness analyses (Also see "NICE Demands "Less Biased" Cost Data On Pradaxa For AF" - Pink Sheet, 17 Aug, 2011.).

This time around, NICE's appraisal committee came to the conclusion that Pradaxa 150 mg twice daily was associated with a statistically significantly lower incidence of stroke or systemic embolism, ischemic stroke and vascular mortality compared with warfarin, which is currently standard care within the NHS. But there were no statistically significant differences between Pradaxa 110 mg twice daily and warfarin, the committee added.

In fact, the committee heard from patient experts that Pradaxa already had a head start on warfarin, because the latter is associated with a number of inconveniences that make adherence difficult. These include numerous food and drug interactions and the need for regular monitoring and dose adjustments. What's more, the committee also noted that both doses of Pradaxa were significantly less likely to cause life-threatening bleeds, compared with warfarin.

Boehringer also submitted a revised cost-effectiveness analysis of its sequential regimen model, comparing Pradaxa with warfarin, as requested by NICE. Whereas it had previously suggested that the upper limit of monitoring for warfarin would be £414.90 ($679.92) per patient per annum, it now gave a revised figure of £241.54 - by contrast, dabigatran is not considered to need monitoring. The new monitoring cost figure appears to have convinced the committee that there is no longer any attempt to bias data in favor of Pradaxa.

Taking the revised figure into account, it means that the incremental cost effectiveness ratio for Pradaxa - compared with warfarin - per quality adjusted life year (QALY) gained in people starting at younger than 80 years of age is £18,900. This is well below the £30,000 limit per QALY gained, which NICE considers to be acceptable.

Boehringer is clearly pleased that it was able to fulfill all of NICE's requests for additional information within a limited period of time and should soon be able to move to market. What's more, Pradaxa appears to have the edge over potential rival Xarelto, which may face problems due to its bleeding risk (Also see "Xarelto's Efficacy Impresses In ACS, But Bleeding Risk Will Complicate Approval" - Pink Sheet, 30 Sep, 2011.). It may, however, be a different ball game with apixaban, which comes up for its NICE assessment in January 2012 (Also see "Apixaban Shows Mortality Advantage, But Will It Survive FDA Scrutiny?" - Pink Sheet, 5 Sep, 2011.).

However, it's not quite over at NICE. Registered consultees now have the opportunity within 15 days to determine whether they wish to appeal against the recommendations in the final draft. Should any do so, and the grounds of their appeal are considered to be valid according to NICE's published process, in theory the guidance could be returned to the independent appraisal committee for further consideration. "In practice, however, a positive decision at FAD stage has never been reversed at FAD stage," a NICE spokesperson confirmed.

- Faraz Kermani ([email protected])