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Expert Review of Clinical Pharmacology Volume 5, 2012 - Issue 6
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Drug Profile

Historical overview of the rationale for the pharmacological use of prolonged-release fampridine in multiple sclerosis

Oscar Fernandez Institute of Clinical Neurosciences, Hospital Regional Universitario Carlos Haya, Spain. [email protected]; Institute of Clinical Neurosciences, Hospital Regional Universitario Carlos Haya, Spain. [email protected]
,
Thomas Berger Clinical Department of Neurology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria; Clinical Department of Neurology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria
,
Hans-Peter Hartung Department of Neurology, Düsseldorf University Hospital, Düsseldorf, Germany; Department of Neurology, Düsseldorf University Hospital, Düsseldorf, Germany
&
Norman Putzki Biogen Idec International, Landis and Gyr-Strasse 3, Zug, Switzerland; Biogen Idec International, Landis and Gyr-Strasse 3, Zug, Switzerland
Pages 649-665 | Published online: 10 Jan 2014

References

  • Dutta R, Trapp BD. Mechanisms of neuronal dysfunction and degeneration in multiple sclerosis. Prog. Neurobiol. 93(1), 1–12 (2011).
  • Degenhardt A, Ramagopalan SV, Scalfari A, Ebers GC. Clinical prognostic factors in multiple sclerosis: a natural history review. Nat. Rev. Neurol. 5(12), 672–682 (2009).
  • Confavreux C, Vukusic S. Age at disability milestones in multiple sclerosis. Brain 129(Pt 3), 595–605 (2006).
  • Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an Expanded Disability Status Scale (EDSS). Neurology 33(11), 1444–1452 (1983).
  • Scalfari A, Neuhaus M, Daumer M et al. Long-term evolution of ‘benign’ multiple sclerosis patients in the London Ontario Database [P01.138]. Presented at: The 64th Annual Meeting of the American Academy of Neurology. LA, USA, 21–28 April 2012.
  • Whetten-Goldstein K, Sloan FA, Goldstein LB, Kulas ED. A comprehensive assessment of the cost of multiple sclerosis in the United States. Mult. Scler. 4(5), 419–425 (1998).
  • Confavreux C, Vukusic S, Adeleine P. Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process. Brain 126(Pt 4), 770–782 (2003).
  • Motl RW, McAuley E. Association between change in physical activity and short-term disability progression in multiple sclerosis. J. Rehabil. Med. 43(4), 305–310 (2011).
  • Kingwell E, van der Kop M, Zhao Y et al. Relative mortality and survival in multiple sclerosis: findings from British Columbia, Canada. J. Neurol. Neurosurg. Psychiatr. 83(1), 61–66 (2012).
  • Tremlett H, Zhao Y, Rieckmann P, Hutchinson M. New perspectives in the natural history of multiple sclerosis. Neurology 74(24), 2004–2015 (2010).
  • Jennum P, Wanscher B, Frederiksen J, Kjellberg J. The socioeconomic consequences of multiple sclerosis: a controlled national study. Eur. Neuropsychopharmacol. 22(1), 36–43 (2012).
  • Piercy J, Rajagopalan K, Pike J et al. Burden of walking problems in MS: analysis of caregiver and indirect costs. Neurology 76(9), A606 (2011).
  • Salter AR, Cutter GR, Tyry T, Marrie RA, Vollmer T. Impact of loss of mobility on instrumental activities of daily living and socioeconomic status in patients with MS. Curr. Med. Res. Opin. 26(2), 493–500 (2010).
  • Larocca NG. Impact of walking impairment in multiple sclerosis: perspectives of patients and care partners. Patient 4(3), 189–201 (2011).
  • Polman CH, Havrdova E, Confavreux C et al. Relationship between Timed 25-Foot Walk walking speed and health-related quality of life in AFFIRM and SENTINEL (#1250). Presented at: The 64th Annual Meeting of the American Association of Neurology. LA, USA, 21–28 April 2012.
  • Jones CA, Pohar SL, Warren S, Turpin KV, Warren KG. The burden of multiple sclerosis: a community health survey. Health Qual. Life Outcomes 6, 1 (2008).
  • Heesen C, Böhm J, Reich C, Kasper J, Goebel M, Gold SM. Patient perception of bodily functions in multiple sclerosis: gait and visual function are the most valuable. Mult. Scler. 14(7), 988–991 (2008).
  • Oliver BJ, Kohli E, Kasper LH. Interferon therapy in relapsing–remitting multiple sclerosis: a systematic review and meta-analysis of the comparative trials. J. Neurol. Sci. 302(1), 96–105 (2011).
  • Polman CH, O’Connor PW, Havrdova E et al.; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med. 354(9), 899–910 (2006).
  • Kappos L, Radue EW, O’Connor P et al.; FREEDOMS Study Group. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N. Engl. J. Med. 362(5), 387–401 (2010).
  • Berger JR. Functional improvement and symptom management in multiple sclerosis: clinical efficacy of current therapies. Am. J. Manag. Care 17(Suppl. 5), S146–S153 (2011).
  • Paisley S, Beard S, Hunn A, Wight J. Clinical effectiveness of oral treatments for spasticity in multiple sclerosis: a systematic review. Mult. Scler. 8(4), 319–329 (2002).
  • Shakespeare DT, Boggild M, Young C. Anti-spasticity agents for multiple sclerosis. Cochrane Database Syst. Rev. 4, CD001332 (2003).
  • Novotna A, Mares J, Ratcliffe S et al.; Sativex Spasticity Study Group. A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex®), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur. J. Neurol. 18(9), 1122–1131 (2011).
  • Wetzel JL, Fry DK, Pfalzer LA. Six-minute walk test for persons with mild or moderate disability from multiple sclerosis: performance and explanatory factors. Physiother. Can. 63(2), 166–180 (2011).
  • Vucic S, Burke D, Kiernan MC. Fatigue in multiple sclerosis: mechanisms and management. Clin. Neurophysiol. 121(6), 809–817 (2010).
  • Bostock H, Sears TA, Sherratt RM. The effects of 4-aminopyridine and tetraethylammonium ions on normal and demyelinated mammalian nerve fibres. J. Physiol. (Lond.) 313, 301–315 (1981).
  • Hayes KC. The use of 4-aminopyridine (fampridine) in demyelinating disorders. CNS Drug Rev. 10(4), 295–316 (2004).
  • Schwid SR, Petrie MD, McDermott MP, Tierney DS, Mason DH, Goodman AD. Quantitative assessment of sustained-release 4-aminopyridine for symptomatic treatment of multiple sclerosis. Neurology 48(4), 817–821 (1997).
  • Compston A, Coles A. Multiple sclerosis. Lancet 359(9313), 1221–1231 (2002).
  • Schwarz JR, Reid G, Bostock H. Action potentials and membrane currents in the human node of Ranvier. Pflugers Arch. 430(2), 283–292 (1995).
  • Karimi-Abdolrezaee S, Eftekharpour E, Fehlings MG. Temporal and spatial patterns of Kv1.1 and Kv1.2 protein and gene expression in spinal cord white matter after acute and chronic spinal cord injury in rats: implications for axonal pathophysiology after neurotrauma. Eur. J. Neurosci. 19(3), 577–589 (2004).
  • Fehlings MG, Nashmi R. Changes in pharmacological sensitivity of the spinal cord to potassium channel blockers following acute spinal cord injury. Brain Res. 736(1-2), 135–145 (1996).
  • Espejo C, Montalban X. Dalfampridine in multiple sclerosis: from symptomatic treatment to immunomodulation. Clin. Immunol. 142(1), 84–92 (2012).
  • Dunn J, Blight A. Dalfampridine: a brief review of its mechanism of action and efficacy as a treatment to improve walking in patients with multiple sclerosis. Curr. Med. Res. Opin. 27(7), 1415–1423 (2011).
  • Wu ZZ, Li DP, Chen SR, Pan HL. Aminopyridines potentiate synaptic and neuromuscular transmission by targeting the voltage-activated calcium channel beta subunit. J. Biol. Chem. 284(52), 36453–36461 (2009).
  • Van Diemen HA, Polman CH, Koetsier JC, Van Loenen AC, Nauta JJ, Bertelsmann FW. 4-aminopyridine in patients with multiple sclerosis: dosage and serum level related to efficacy and safety. Clin. Neuropharmacol. 16(3), 195–204 (1993).
  • Hayes KC, Katz MA, Devane JG et al. Pharmacokinetics of an immediate-release oral formulation of fampridine (4-aminopyridine) in normal subjects and patients with spinal cord injury. J. Clin. Pharmacol. 43(4), 379–385 (2003).
  • Donnelly R. Chemical stability of 4-aminopyridine capsules. Can. J. Hosp. Pharm. 57, 283–287 (2004).
  • Uges DR, Sohn YJ, Greijdanus B, Scaf AH, Agoston S. 4-aminopyridine kinetics. Clin. Pharmacol. Ther. 31(5), 587–593 (1982).
  • Bever CT Jr, Young D, Anderson PA et al. The effects of 4-aminopyridine in multiple sclerosis patients: results of a randomized, placebo-controlled, double-blind, concentration-controlled, crossover trial. Neurology 44(6), 1054–1059 (1994).
  • Blight AR, Henney HR 3rd. Pharmacokinetics of 14C-radioactivity after oral intake of a single dose of 14C-labeled fampridine (4-aminopyridine) in healthy volunteers. Clin. Ther. 31(2), 328–335 (2009).
  • Judge SI, Lee JM, Bever CT Jr, Hoffman PM. Voltage-gated potassium channels in multiple sclerosis: overview and new implications for treatment of central nervous system inflammation and degeneration. J. Rehabil. Res. Dev. 43(1), 111–122 (2006).
  • Bever CT, Judge SI. Sustained-release fampridine for multiple sclerosis. Expert Opin. Investig. Drugs 18(7), 1013–1024 (2009).
  • Polman CH, Bertelsmann FW, van Loenen AC, Koetsier JC. 4-aminopyridine in the treatment of patients with multiple sclerosis. Long-term efficacy and safety. Arch. Neurol. 51(3), 292–296 (1994).
  • Schwam E. Severe accidental overdose of 4-aminopyridine due to a compounding pharmacy error. J. Emerg. Med. 41(1), 51–54 (2011).
  • Smith W, Swan S, Marbury T, Henney H 3rd. Single-dose pharmacokinetics of sustained-release fampridine (fampridine-SR) in healthy volunteers and adults with renal impairment. J. Clin. Pharmacol. 50(2), 151–159 (2010).
  • Vollmer T, Blight AR, Henney HR 3rd. Steady-state pharmacokinetics and tolerability of orally administered fampridine sustained-release 10-mg tablets in patients with multiple sclerosis: a 2-week, open-label, follow-up study. Clin. Ther. 31(10), 2215–2223 (2009).
  • Vollmer T, Henney HR 3rd. Pharmacokinetics and tolerability of single escalating doses of fampridine sustained-release tablets in patients with multiple sclerosis: a Phase I–II, open-label trial. Clin. Ther. 31(10), 2206–2214 (2009).
  • Goodman AD, Brown TR, Edwards KR et al.; MSF204 Investigators. A Phase 3 trial of extended release oral dalfampridine in multiple sclerosis. Ann. Neurol. 68(4), 494–502 (2010).
  • Zolk O, Solbach TF, König J, Fromm MF. Functional characterization of the human organic cation transporter 2 variant p.270Ala>Ser. Drug Metab. Dispos. 37(6), 1312–1318 (2009).
  • Kido Y, Matsson P, Giacomini KM. Profiling of a prescription drug library for potential renal drug–drug interactions mediated by the organic cation transporter 2. J. Med. Chem. 54(13), 4548–4558 (2011).
  • Davis FA, Stefoski D, Rush J. Orally administered 4-aminopyridine improves clinical signs in multiple sclerosis. Ann. Neurol. 27(2), 186–192 (1990).
  • Jones RE, Heron JR, Foster DH, Snelgar RS, Mason RJ. Effects of 4-aminopyridine in patients with multiple sclerosis. J. Neurol. Sci. 60(3), 353–362 (1983).
  • Goodman AD, Cohen JA, Cross A et al. Fampridine-SR in multiple sclerosis: a randomized, double-blind, placebo-controlled, dose-ranging study. Mult. Scler. 13(3), 357–368 (2007).
  • Goodman AD, Brown TR, Krupp LB et al.; Fampridine MS-F203 Investigators. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet 373(9665), 732–738 (2009).
  • Goodman AD, Brown TR, Cohen JA et al.; Fampridine MS-F202 Study Group. Dose comparison trial of sustained-release fampridine in multiple sclerosis. Neurology 71(15), 1134–1141 (2008).
  • Fischer JS, Rudick RA, Cutter GR, Reingold SC. The Multiple Sclerosis Functional Composite Measure (MSFC): an integrated approach to MS clinical outcome assessment. National MS Society Clinical Outcomes Assessment Task Force. Mult. Scler. 5(4), 244–250 (1999).
  • Hobart JC, Riazi A, Lamping DL, Fitzpatrick R, Thompson AJ. Measuring the impact of MS on walking ability: the 12-Item MS Walking Scale (MSWS-12). Neurology 60(1), 31–36 (2003).
  • Hobart JC. Prolonged-release fampridine for multiple sclerosis: was the effect on walking ability clinically significant (P509). Mult. Scler. 16, S7–S39, S172 (2010).
  • Limmroth V, Putzki N, Goodman AD. Data from prolonged-release fampridine trials confirm that 20% improvement in walking speed is clinically meaningful. Presented at: The 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis. Amsterdam, The Netherlands, 19–22 October 2011.
  • Hobart JC, Blight AR, Lynn F et al. The Timed 25-Foot Walk as an outcome measure for clinical trials in multiple sclerosis: further evidence that a 20% change is clinically meaningful. Presented at: The 21st Meeting of the European Neurological Society. Lisbon, Portugal, 28–31 May 2011.
  • Goodman AD. Updated analysis of open-label extension studies of dalfampridine extended release tablets in multiple sclerosis. Presented at: The 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis. Amsterdam, The Netherlands, 19–22 October 2011.
  • Goodman AD, Brown TR, Edwards KR et al. Analysis of open-label extension studies of prolonged release fampridine tablets in multiple sclerosis. Mult. Scler. 16, S175 (2010).
  • Goodman AD, Blight A. Final Data from Open-label extension studies of dalfampridine extended release tablets in multiple sclerosis [P04.128]. Presented at: The 64th Annual Meeting of the American Academy of Neurology. LA, USA, 21–28 April 2012.
  • Cohen JA, Cutter GR, Fischer JS et al.; IMPACT Investigators. Benefit of INF-𝛃-1a on MSFC progression in secondary progressive MS. Neurology 59(5), 679–687 (2002).
  • Krishnan A, Goodman AD, Potts J et al. Health-related quality of life is reduced in multiple sclerosis patients whose walking speed declines over time. Presented at: The 64th Annual Meeting of the American Association of Neurology. LA, USA, 21–28 April 2012.
  • Lucchinetti C, Brück W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann. Neurol. 47(6), 707–717 (2000).
  • Stourac P, Putzki N. Prolonged-release fampridine shows consistent efficacy across subgroups of multiple sclerosis patients. Presented at: The 22nd meeting of the European Neurological Society. Prague, Czech Republic, 9–12 June 2012.
  • Koch C, Uyttenboogaart M, Polman S, De Keyser J. Seizures in multiple sclerosis. Epilepsia 49(6), 948–958 (2008).
  • Jara M, Adera M, Adedeji A, Henney HR 3rd, Carrazana EJ. Dalfampridine extended release tablets: safety profile after 2 years of postmarketing experience in the United States. Presented at: The 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis. Lyon, France, 10–13 October 2012.
  • Cattaneo D, Regola A, Meotti M. Validity of six balance disorders scales in persons with multiple sclerosis. Disabil. Rehabil. 28(12), 789–795 (2006).
  • Stefoski D, Davis FA, Faut M, Schauf CL. 4-aminopyridine improves clinical signs in multiple sclerosis. Ann. Neurol. 21(1), 71–77 (1987).
  • Stefoski D, Davis FA, Fitzsimmons WE, Luskin SS, Rush J, Parkhurst GW. 4-aminopyridine in multiple sclerosis: prolonged administration. Neurology 41(9), 1344–1348 (1991).
  • van Diemen HA, Polman CH, van Dongen TM et al. The effect of 4-aminopyridine on clinical signs in multiple sclerosis: a randomized, placebo-controlled, double-blind, cross-over study. Ann. Neurol. 32(2), 123–130 (1992).

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