NICE Issues Positive FAD for Fingolimod after Novartis Relents and Offers PAS

Fingolimod to See Light of Day As NICE Has Change of Heart

The United Kingdom's National Institute for Health and Clinical Excellence (NICE) has indicated plans to recommend the funding of Swiss pharma Novartis's Gilenya (fingolimod) in a final appraisal determination (FAD) issued today (16 March). The FAD (available here) is in contrast to the previous view in draft guidance , which indicated that Gilenya was set for rejection.

In the FAD, NICE's appraisal committee indicates that fingolimod should be recommended as an option for the treatment of highly active relapsing-remitting multiple sclerosis in adults, only if patients have an unchanged or increased relapse rate or ongoing severe relapses compared with the previous year, despite treatment with beta interferon. The positive recommendation is subject to a patient access scheme (PAS) provided by the manufacturer, which makes fingolimod available at a discount to the National Health Service.

The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) for fingolimod in the manufacturer's original submission was as high as GBP73,191 (USD115,526.73) and GBP85,266 per QALY gained when treatment efficacy was assumed to be reduced by a respective 50% or 75%. It reached GBP97,159 and GBP64,280 per QALY gained when the time horizon was shortened to 10 years and 20 years, respectively.

In response to the first appraisal consultation document, Novartis offered a PAS including a simple discount that remains confidential. With the cost of the drug under the PAS applied, the manufacturer's deterministic base-case ICER for fingolimod in population 1b was reduced to GBP10,839 per QALY gained, compared with Avonex. The probabilistic ICER determined by the manufacturer, including the PAS, was GBP15,825 per QALY gained. At the suggestion of NICE's Evidence Review Group (ERG), the manufacturer also reworked its model to include utility data from the trials where available, and then published data from Orme et al (2007) for the remaining Expanded Disability Status Scale states, while also assuming a 50% reduction in treatment effect at five years.

In response to the second appraisal consultation document, Novartis also explored the directional effect on the ICER of changing the natural history transition matrix to slow disability progression. Also at the ERG's suggestion, the manufacturer provided analyses only for population 1b, excluding patients who also met the criteria for population 2.

After reviewing the additional data, the NICE appraisal committee concluded that the most plausible ICER for fingolimod compared with the weighted average of the comparators was likely to be in the range of GBP25,000–35,000 per QALY gained.

Outlook and Implications

The discount offered by the company has clearly been instrumental in triggering a change of mind by the UK's influential health technology assessment agency. Novartis has offered the PAS relatively late in the game—after two negative draft reviews—in what is clearly a trend with NICE reviews. A PAS is offered at the last minute, when a NICE rejection is clearly forthcoming. Even with the discount offered, NICE is set to recommend the reimbursement of Gilenya in only a subset of the treatable population: population 1b, for whom the cost-effectiveness case was better demonstrated. Population 1b includes adults who have an unchanged or increased relapse rate, or ongoing severe relapses compared with the previous year, despite previous treatment with beta interferon.