Key points

Key points

The content of this evidence summary was up-to-date in February 2017. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.

Regulatory status: New medicine. Safinamide is a monoamine oxidase‑B (MAO‑B) inhibitor. It received a European marketing authorisation in February 2015 and was launched in the UK in May 2016. It is licensed for treating mid- to late-stage idiopathic Parkinson's disease in adults who are experiencing motor fluctuations, as an add-on treatment to a stable dose of levodopa when used either on its own or in combination with other Parkinson's disease medicines.

Overview

This evidence summary discusses 3 randomised controlled trials (RCTs) in people with Parkinson's disease of at least 3 years duration, who were taking a stable dose of levodopa and were experiencing motor fluctuations. Most people in the studies were also taking other Parkinson's disease medicines, most commonly a dopamine agonist. There is limited data on the use of safinamide as a first choice add-on treatment to levodopa.

The main clinical benefits of safinamide at 24 weeks were an increase in 'on time' without troublesome dyskinesia (involuntary movements) of approximately 30 to 60 minutes daily, and a similar reduction in 'off time', compared with placebo. This effect was still observed at a 2-year follow‑up.

Dyskinesia was the most commonly reported adverse effect, but was usually mild and associated with an increase in on time. Contraindications and cautions for use are similar to those of other MAO‑B inhibitors. There is a potential risk of retinal degeneration in people with, or a previous history of, retinal disease with safinamide.

Safinamide is the third MAO-B inhibitor licensed in the UK as add-on treatment to levodopa in people with Parkinson's disease who are experiencing motor fluctuations. It is more expensive than other MAO‑B inhibitors: 30-day treatment costs are £3.38, £9.67 and £69.00 for rasagiline, selegiline and safinamide respectively (Drug Tariff, February 2017; excluding VAT).

There are no head‑to‑head studies comparing the efficacy and safety of safinamide with other active treatments, including other MAO‑B inhibitors. The NICE guideline on Parkinson's disease makes recommendations on the place in therapy of adjuvant treatments. The choice of treatment will depend on the person's clinical and lifestyle characteristics, and their preferences, after an informed discussion about the benefits and risks of treatment.

A framework to inform local decision-making is shown in table 1.

Table 1 Summary of the evidence on effectiveness, safety, patient factors and resource implications

Effectiveness

  • Safinamide was more effective than placebo at improving on time without troublesome dyskinesia by approximately 30 to 60 minutes daily (from a baseline of about 9 hours daily) at 24 weeks and 2 years follow‑up. There were similar reductions in off time (3 RCTs: study 016, SETTLE study, study 018, total n=1,218).

  • Safinamide did not improve dyskinesia in the 3 RCTs (measured by DRS total score) compared with placebo. This was the primary outcome of study 018.

  • In study 016 and SETTLE, safinamide improved motor symptoms during on time (by about 2 points on UPDRS-III) compared with placebo at 24 weeks (from a baseline of 22 to 29 points). This improvement was still observed at 2 years only in the safinamide 100 mg daily group.

  • Safinamide 100 mg or 50–100 mg was more effective than placebo at improving health‑related quality of life (measured by PDQ-39). There was no statistically significant difference between safinamide 50 mg and placebo (3 RCTs).

  • More people had improvement in clinical global impression (measured by CGI-C) with safinamide compared with placebo at 24 weeks; this was statistically significant. This difference was still observed at 2 years only in the safinamide 50 mg daily group.

Safety

  • The SPC states that safinamide is contraindicated in severe hepatic impairment and should be used with caution in moderate hepatic impairment.

  • Safinamide is also contraindicated in people with albinism, retinal degeneration, uveitis, inherited retinopathy or severe progressive diabetic retinopathy; and with other MAO inhibitors or pethidine.

  • The SPC states that safinamide used as an adjunct to levodopa may potentiate the adverse effects of levodopa, and pre-existing dyskinesia may be exacerbated.

Patient factors

  • Common adverse effects reported in the SPC are dyskinesia, insomnia, nausea, somnolence, dizziness, headache, Parkinson's disease symptoms, cataracts, orthostatic hypotension and falls.

  • Impulse control disorders have been seen with other MAO inhibitors, and patients and carers should be made aware of the behavioural symptoms of these.

  • Safinamide can be used without any dietary tyramine restrictions.

  • Safinamide has not been investigated in people with severe, disabling peak dose or biphasic dyskinesia with unpredictable or wide fluctuations; people with a history or presence of retinal disease; or people with psychiatric illness, bipolar disorder or severe depression.

Resource implications

  • The NHS list price for safinamide 50 mg or 100 mg is £69.00 for 30 tablets (Drug Tariff, February 2017; excluding VAT).

  • The 30-day cost of other MAO‑B inhibitors is £3.38 for rasagiline 1 mg daily and £9.67 for selegiline 10 mg daily (Drug Tariff, February 2017; excluding VAT).