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Commissioning Support
Fampridine-SR (Fampyra®▼)
For the treatment of walking disability in
multiple sclerosis
Commissioning and prescribing considerations
Committee’s Verdict: CATEGORY C (Q4)
Category C: Not suitable for prescribing in primary care
Q rating: The evidence for the efficacy of fampridine was considered to
be relatively weak, based on three placebo-controlled randomised trials.
In all three trials significantly more fampridine patients showed a
response to treatment compared with placebo (faster walking speeds ‘on
treatment’ vs. ‘off treatment’). The mean maximum improvements in
walking speed were small: 0.18 feet/second (ft/s) in placebo-treated
patients and 0.31 ft/s in fampridine-treated patients. Given that
fampridine should be initiated and monitored in a specialist setting, it has a
low place in therapy in primary care.
Place in therapy in primary care
In making decisions regarding the use of fampridine in patients with multiple sclerosis (MS), the following should be
considered:
 Fampridine should be initiated and monitored in a specialist MS care setting.
 Stopping rules should be included in care plans, and agreed with the patient upon initiation of treatment.
 The patient should be asked to complete a timed 25-foot walk test to establish a baseline three months
before initiation of treatment, and on initiation of treatment. The patient should be tested two weeks after
initiation of fampridine for a response to treatment (e.g. a 20% improvement in walking speed vs. baseline).
 Further timed 25-foot walk tests should be performed after three and six months of treatment, or during
routine clinic appointments. Fampridine treatment should be stopped if the patient does not show a
response initially, or if the response is not maintained at the three-month test.
 If there is deterioration in the patient’s walking speed in routine testing, fampridine treatment should be
stopped and the patient re-tested.
Q2
higher place
weaker evidence
Q1
higher place
stronger evidence
Q4
lower place
weaker evidence
Q3
lower place
stronger evidence
Strength of evidence for efficacy
The Q rating relates to the drug’s position on the effectiveness indicator grid. The strength of the evidence is determined
by the quality and quantity of studies that show significant efficacy of the drug compared with placebo or alternative therapy. Its
place in therapy in primary care takes into account safety and practical aspects of using the drug in primary care, alternative
options, relevant NICE guidance, and the need for secondary care input.
MTRAC reviewed fampridine because of the concerns of prescribers and commissioners regarding its efficacy and place in
therapy.
Description of technology
Fampridine-SR is a prolonged-release formulation of
4-aminopyridine, licensed for the improvement of
walking in adult patients with multiple sclerosis with a
walking disability score of 4 to 7 on the Expanded
1
Disability Status Scale (EDSS). It is a selective
potassium channel blocker.
Clinical efficacy
Background information
Multiple sclerosis is an autoimmune disease of the
central nervous system in which inflammation
destroys the protective sheath surrounding nerve
cells.
Problems with mobility are very common in MS and
can be caused by muscle weakness, muscle stiffness
(spasticity) or problems with balance. Many other
symptoms of MS can affect balance and mobility,
including fatigue, pain, altered sensation, visual
2
disturbances, mood and vertigo.
The NICE clinical guideline on multiple sclerosis,
May 2012
published in 2003, recommended that all patients
should be assessed by a specialist neurological
rehabilitation service and receive: advice and
education to manage their condition, provision of
suitable equipment and alterations to their living
environment, and physiotherapy. Carers should also
receive advice and education.
3
Three double-blind, placebo-controlled RCTs
evaluated the efficacy of fampridine-SR as a
treatment to improve walking speed in patients with
4-6
MS.
One trial was a phase 2 trial, evaluating
fampridine-SR at doses of 10, 15 or 20 mg twice
5
daily [15 and 20 mg doses are unlicensed]; the other
trials were phase 3 trials that evaluated fampridine-SR
4,6
10 mg twice daily. Included patients had
progressive or relapsing-remitting MS that was
currently in a stable phase, an average EDSS of 5.8,
and were able to complete two, timed 25-foot walk
tests. Patients with a history of seizures, or who
Page 1 of 2
showed epileptiform activity on electroencephalogram
(EEG) were excluded. Following screening and a
two-week placebo run-in period, the double-blind
treatment phase lasted 9 to 14 weeks, with two to four
weeks’ follow up. Patients were given timed 25-foot
walk tests before, during and after treatment. The
primary outcome measure in two trials was the
number of patients who showed a response to
treatment, defined as a faster walking speed for at
least three of four timed 25-foot walk tests whilst on
4,6
treatment compared with off-treatment periods. In
the third trial, the primary outcome was the
5
percentage change in walking speed. In this trial,
response to treatment was measured in a post-hoc
analysis. Other outcome measures across the trials
were the 12-item Multiple Sclerosis Walking Scale
(MSWS-12), the Ashworth score for spasticity, the
Lower Extremity Manual Muscle Test indicating
muscle strength (LEMMT), and the subject and
clinician’s global impression of change. Where the
results did not show a clear comparison between
fampridine-SR and placebo in trial reports, additional
data from the European Medicines Agency public
7
assessment report for fampridine were assessed.
Response to treatment: In all three trials,
significantly more fampridine-treated patients showed
a response to treatment than those receiving placebo
4-6
(35 to 43% vs. 8 to 9% respectively, p < 0.05).
Walking speed: The improvement in mean walking
speed from baseline was significantly greater with
fampridine treatment than placebo in two trials
4,6
(p < 0.05). Across the trials, mean walking speeds
were improved by 0.09 to 0.31 feet/second (ft/s) in
fampridine-treated patients compared with 0.04 to
0.18 ft/s in placebo-treated patients; baseline walking
7
speeds were 1.8 to 2.2 ft/s.
MSWS-12: One of three trials showed a significantly
greater improvement in the MSWS-12 score in
fampridine-treated patients compared with placebo
7
(p = 0.006).
LEMMT: Two of three trials showed significantly
greater improvement in LEMMT scores in fampridine7
treated patients compared with placebo (p < 0.01).
Ashworth score: One of three trials found a
significantly greater improvement in the Ashworth
spasticity score for fampridine-treated patients
6
compared with placebo (p = 0.015).
Adverse effects
dizziness, paraesthesia, tremor, headache and
asthenia. The Summary of Product Characteristics
(SPC) states that treatment with fampridine-SR
1
increases seizure risk; it should be administered with
caution in the presence of any factors which may
lower seizure threshold. Additional precautions in the
SPC are that fampridine-SR should be administered
with caution to patients with cardiovascular symptoms
of rhythm and sinoatrial or atrioventricular conduction
cardiac disorders. There is an increased incidence of
dizziness and balance disorders seen with fampridineSR in the first four to eight weeks of treatment, which
1
may result in an increased risk of falls.
Considerations for cost impact
 The estimated prevalence of patients with MS in
the West Midlands is about 10,000 people (10% of
2
national prevalence ). Based on estimates,
potentially 5,700 patients may be eligible for
fampridine treatment.
 At current prices, a years’ treatment for one patient
with fampridine-SR 20 mg daily would cost £4,719
(excluding VAT and assessment costs).
Reference
1.
2.
3.
4.
5.
6.
7.
About 507 patients have been exposed to fampridineSR in the trials reviewed. The most common adverse
event was urinary tract infection. Other frequent
adverse events were mostly neurological and included
seizure, insomnia, anxiety, balance disorder,
Biogen Idec Ltd. Fampyra 10 mg prolonged-release
tablets. EMC. 2012.
http://www.medicines.org.uk/EMC/medicine/25003/S
PC/Fampyra+10+mg+prolonged-release+tablets/
<accessed 3/2012>
Multiple sclerosis – the quick guide. Multiple
Sclerosis Society. 2011.
http://www.mssociety.org.uk/sites/default/files/Docum
ents/Professionals/MS%20%20the%20quick%20guide%201211%20%20web.pdf
National Collaborating Centre for Chronic Conditions.
CG8: Management of multiple sclerosis in primary
and secondary care. NICE. 2003.
http://www.nice.org.uk/nicemedia/live/10930/29199/2
9199.pdf
Goodman AD, Brown TR, Krupp LB et al. Sustainedrelease oral fampridine in multiple sclerosis: a
randomised, double-blind, controlled trial. Lancet
2009;373:732-8.
Goodman AD, Brown TR, Cohen JA et al. Dose
comparison trial of sustained-release fampridine in
multiple sclerosis. Neurology 2008;71:1134-41.
Goodman AD, Brown TR, Edwards KR et al. A
phase 3 trial of extended release oral dalfampridine
in multiple sclerosis. Ann Neurol 2010;68:494-502.
Fampyra Assessment Report (EMEA/H/C/002097).
European Medicines Agency. 2011.
http://www.ema.europa.eu/docs/en_GB/document_lib
rary/EPAR__Public_assessment_report/human/002097/WC5001
09957.pdf <accessed 4/2012>
Launch date: November 2011
Manufacturer: Biogen Idec Ltd
EU/1/11/699/001,002
WARNING: This sheet should be read in conjunction with the Summary of Product Characteristics
This guidance is based upon the published information available in English at the time the drug was considered. It remains
open to review in the event of significant new evidence emerging.
MTRAC can be contacted at the Dept. of Medicines Management, School of Pharmacy, Keele University, Keele, Staffs ST5 5BG
Tel: 01782 734131 Email: [email protected] Web: www.mtrac.co.uk
NICE GUIDANCE ON FAMPRIDINE WAS NOT AVAILABLE AT THE TIME OF ISSUE OF THIS COMMISSIONING SUPPORT DOCUMENT
Date: May 2012
©Midlands Therapeutics Review & Advisory Committee