The first oral treatment for multiple sclerosis (MS) has been given the green light by UK regulators and is now available in the UK. Fingolimod0.5 mg (Gilenya™) has been authorised for people with highly active relapsing remitting multiple sclerosis (RRMS) who have failed to respond to an interferon (injection), or for those with rapidly evolving severe disease.6

Fingolimod provides a new treatment option for patients failing on injections but whose disease is not severe enough for infusion therapy. Patients on an interferon need to have had one or more relapses within the last year to be eligible for treatment with fingolimod.6

Fingolimod is a new class of drug called a sphingosine 1-phosphate (S1P) receptor modulator that works in a completely different way to any other MS treatment.1,2 As fingolimod is an immunomodulator, it does not kill lymphocytes but retains them in the lymph nodes thereby preserving key immune functions.7,8,9

The cells that have been retained can be rapidly released from the glands when treatment is stopped, which means that:9
  • Women can start trying to get pregnant two months after treatment is stopped
  • Physicians have the flexibility to try new treatments if required
In addition, fingolimod does not stop all immune cells from circulating within a patient's body and therefore people treated with fingolimod should have adequate immunity to respond to most infections.8

The authorisation of fingolimod was based on the submission of data from a large clinical trial programme, which included the TRANSFORMS and FREEDOMS studies.3,10
  • TRANSFORMS showed that fingolimod 0.5 mg reduced the annualised relapse rate by 52% compared to interferon β-1a IM - This equates to a reduction in annualised relapse rate from 0.33 for interferon beta-1a IM to 0.16 with fingolimod 0.5 mg
  • FREEDOMS showed that fingolimod 0.5 mg dose reduced the annualised relapse rate by 54% versus placebo and reduced disability progression by 30% - This is equivalent to a reduction in annualised relapse rate from 0.40 for placebo to 0.18 with fingolimod 0.5 mg
The cost of managing multiple sclerosis includes the cost of treating relapses (relapses requiring hospitalisation are estimated to cost the NHS £3,034 per episode),11 the price of disease modifying therapies and any associated administration costs of each drug. Currently, patients who fail on an interferon but who are not right for infusion therapy have limited treatment options. This gap in treatment is because the National Institute of Clinical Excellence (NICE) stipulates that people with RRMS who continue to experience relapses on an injection are not eligible for second line infusion therapy, unless their disease is classified as rapidly evolving and severe (TA127).12

Fingolimod is available to appropriate patients in the UK from today and neurologists can apply now for treatment reimbursement via individual funding requests. NICE is currently reviewing fingolimod and will issue draft guidance in July 2011.13

Licenced indication for fingolimod6

Fingolimod has been licenced for use as a single therapy in the treatment of highly active RRMS in the following adult groups:
  • Patients with high disease activity despite treatment with an interferon (defined on MRI imaging or relapse frequency)
  • Patients with rapidly evolving severe disease (defined by MRI imaging, relapse rate and severity)
Safety profile of fingolimod3,4,5,10

The clinical trial programme demonstrated that fingolimod is generally well tolerated with a manageable safety profile. Its risk/benefit profile has been studied in more than 4,000 clinical trial patients, some of whom are in their seventh year of treatment. The most common side effects are headache, liver enzyme elevations, influenza, diahorrea, back pain, and cough. Other fingolimod-related side effects include transient, generally asymptomatic, heart rate reduction and atrioventricular block upon treatment initiation, mild blood pressure increase, macular oedema, and mild bronchoconstriction. The rates of infections overall, including serious infections, were comparable among treatment groups, although a slight increase in lung infections (primarily bronchitis) was seen in patients treated with fingolimod.

References
  1. Foster CA et al. Brain penetration of the oral immunomodulatory drug FTY720 and its phosphorylation in the central nervous system during experimental autoimmune encephalomyelitis: consequences for mode of action in multiple sclerosis. J Pharmacol Exp Ther 2007, 323 (2) 469-76
  2. MS Society Fact Sheet - Fingolimod. http://www.mssociety.org.uk/research/fact_sheets.html Last accessed 09 February 2011
  3. Cohen JA et al. Oral Fingolimod vs. intramuscular interferon in relapsing multiple sclerosis. N Eng J Med 2010, 362 (5) 405-415
  4. Novartis data on file
  5. O'Connor P et al. Oral fingolimod (FTY720) in MS. Two-year results of a phase II extension study. Neurology. 2009, 72; 73-79
  6. Gilenya Summary of Product Characteristics. 2011 http://www.medicines.org.uk/EMC/medicine/24443/SPC/Gilenya+0.5mg+hard+capsules Last accessed 11 April 2011
  7. http://guidance.nice.org.uk/TA/Wave20/71/Scope/pdf/English Last accessed 1 April 2011
  8. Brinkman V. FTY720 (fingolimod) in multiple sclerosis: therapeutic effects in the immune and the central nervous system. Brit J Pharm (2009), 158, 1173-1182
  9. Schmouder R et al. Pharmacodynamic effects of oral fingolimod (FTY720). Poster presented at 22nd meeting of the European Committee for treatment and research in multiple sclerosis (ECTRIMS), Madrid, Spain, 27-30 September 2006
  10. Kappos L et al. Placebo-controlled study of oral fingolimod in relapsing multiple sclerosis. N Eng J Med 2010, 362 (5) 387-401
  11. Department of Health. NHS payment by results 2011-12 national tariff information. 23 March 2011. Available at: http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_125398.xls last accessed 4 April 2011
  12. http://www.nice.org.uk/nicemedia/live/11822/36136/36136.pdf Last accessed 1 April 2011
  13. http://guidance.nice.org.uk/TA/Wave20/71 Last accessed 1 April 2011
Source
Novartis