AMPYRA PPT bytes Brand Generic sclerosis by mikeholy

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									         Ampyra™
      (dalfampridine)
Note: previously researched as Fampridine


      Manufacturer: Acorda

FDA Approval Date: January 2010
                  Ampyra™ (dalfampridine)

                     Drug Facts

Pharmacology
• Mechanism not fully known
• Dalfampridine is a broad spectrum potassium channel blocker.
• In animal studies, it has been shown to increase conduction of
  action potentials in demyelinated axons through inhibition of
  potassium channels.
            Ampyra™ (dalfampridine)

        Clinical Application

• Indications:
  • Treatment to improve walking in patients
    with multiple sclerosis (MS), demonstrated
    by an increase in walking speed
• Place in therapy:
  • 1st line for improvement in walking but use
    may be limited due to its high cost
             Ampyra™ (dalfampridine)

         Clinical Application

• Contraindications:
  • History of seizure
  • Moderate or severe renal impairment
    (CrCl≤50mL/min)
• Warnings and Precautions:
  • Seizures
  • Renally impaired pts
  • UTI
               Ampyra™ (dalfampridine)

                   Drug Facts
Pharmacokinetics

 A             Rapid and complete. F=96%.
       Largely unbound to plasma proteins (97-99%).
 D
                      Vd = 2.6L/kg.
     No active metabolites. t1/2= 5.2-6.5h, prolonged in
 M
        severe renal impairment (~3 times longer).
     Urine (96%; 90% of total dose as unchanged drug);
 E
                       feces (0.5%)
                 Ampyra™ (dalfampridine)

             Adverse Effects

Common Adverse Effects:
                         Dalfampridine (%)   Placebo (%)
      UTI                       12               8
      Insomnia                  9                4
      Dizziness                 7                4
      Headache                  7                4
      Nausea                    7                3
      Asthenia                  7                4
      Back pain                 5                2
      Balance disorder          5                1
            Ampyra™ (dalfampridine)

     Monitoring Parameters

• Efficacy Monitoring
  • Walking speed, measured by timed-25-
    foot-walk (T25FW)


• Toxicity Monitoring
  • New onset seizure (monitor SCr)
           Ampyra™ (dalfampridine)

    Prescription Information

• Dosing
  • 10mg PO BID
• Cost
  • ~$1,300/month
  • ~$15,000/year
             Ampyra™ (dalfampridine)

                Summary
• First novel agent to treat ambulatory
  dysfunction in MS, which is among the most
  common MS symptoms
• Indicated for symptomatic relief to improve
  walking in MS pts and is not considered a
  disease modifying treatment
• Administration is associated with a dose-
  dependent risk of seizure
• Contraindicated in patients with history of
  seizure and moderate-severe renal impairment
                  Ampyra™ (dalfampridine)
                  Trial Information

Sustained-release oral fampridine in multiple sclerosis: a
        randomised, double-blind, controlled trial

Objective:
• Assess efficacy and safety of oral, sustained-release fampridine
   in people with ambulatory deficits due to multiple sclerosis
Trial Design:
• Randomized, multicenter, double-blind, controlled phase III trial
• 301 pts with any type of MS were randomly assigned to 14
   weeks of treatment with either fampridine (10mg BID; n=229) or
   placebo (n=72)


                                                Goodman AD, et al. Lancet 2009; 373:732-38
               Ampyra™ (dalfampridine)
               Trial Information

Inclusion Criteria:
• 18-70yo pts with definite MS
• Must be able to complete 2 trials of the timed 25-foot
  walk (T25FW) at screening within 8-45 seconds

Exclusion Criteria:
• Onset of MS exacerbation within 60 days of screening
• History of seizures or epileptiform activity on EEG



                                         Goodman AD, et al. Lancet 2009; 373:732-38
              Ampyra™ (dalfampridine)
             Trial Information

Intervention:
• Dalfampridine 10mg BID or placebo for 14 weeks




                                        Goodman AD, et al. Lancet 2009; 373:732-38
              Ampyra™ (dalfampridine)
              Trial Information

Primary Efficacy Endpoint:
• Response, based changes in walking speed (ft/sec),
  assessed by T25FW

Secondary Efficacy Endpoint:
• Ashworth score for spasticity
• Lower extremity manual muscle test (LEMMT)
• 12-item multiple sclerosis walking scale (MSWS-12)



                                        Goodman AD, et al. Lancet 2009; 373:732-38
                  Ampyra™ (dalfampridine)
                  Trial Information

Demographics
 and Baseline
Characteristics




                                            Goodman AD, et al. Lancet 2009; 373:732-38
                       Ampyra™ (dalfampridine)
                      Trial Information



                                                    p<0.0001; Mantel-Haenszel
                                                    OR 4.5; 95% CI 2.08-10.86




Primary
            Placebo   Ampyra   RR%    ARR%   OR            CI            p-value          NNT
Endpoint
Responder     8%      34.8%    4.35   26.8   4.75      2.08-10.86       P<0.0001            4

                                                           Goodman AD, et al. Lancet 2009; 373:732-38
Ampyra™ (dalfampridine)
Trial Information
                                                  Δ       95% CI
                                                 (%)
                              Placebo            4.7      1.0-8.4
                          Fampridine NR          7.5     5.0-10.0
                           Fampridine R         25.2       21.5-
                                                           28.8




                          Goodman AD, et al. Lancet 2009; 373:732-38
                 Ampyra™ (dalfampridine)
                 Trial Information
Secondary Outcome Results:
• LEMMT
   • Fampridine-treated responder group showed improved leg
     strength compared with the placebo group (0.18 vs 0.04,
     p=0.0002)
   • Fampridine-treated non-responder group also showed
     improved leg strength compared with the placebo group
     (0.11, p=0.046)
• Average Ashworth score improved in fampridine-treated timed
  walk responder and non-responder groups more than that in the
  placebo group, but this difference was not significant for the
  responder group


                                              Goodman AD, et al. Lancet 2009; 373:732-38
          Ampyra™ (dalfampridine)
          Trial Information


Adverse
 Events




                                    Goodman AD, et al. Lancet 2009; 373:732-38
             Ampyra™ (dalfampridine)
             Trial Information

Study Limitations:
• Long term safety and efficacy data not
  established
• Study population limited to patients in the US
  and Canada




                                       Goodman AD, et al. Lancet 2009; 373:732-38
               Ampyra™ (dalfampridine)
              Trial Information

Trial Conclusions:
• Treatment produces clinically meaningful improvement
  in walking ability in some people with MS
• Fampridine improved walking speed in significantly
  more patients than placebo (34.8% vs. 8.3%), p<0.001
• Of the responders, the degree of improvement (average
  change in walking speed) was about 25% (vs placebo
  5%), 95% CI 21.5-28.8




                                         Goodman AD, et al. Lancet 2009; 373:732-38
               Ampyra™ (dalfampridine)
                    Summary

• First agent to treat ambulatory dysfunction in MS
• Improved walking speed in significantly more patients
  than placebo (34.8% vs. 8.3%)
• Of the responders, there was a significant degree of
  improvement: 25% vs 5% change in walking speed
• Contraindicated in patients with history of seizure and
  moderate-severe renal impairment
• Dosing is 10mg PO BID
• Use may be limited due to high cost (~$1300/month)
              Ampyra™ (dalfampridine)

                 References

1. http://www.ampyra.com
2. Ampyra package insert. Acorda Therapeutics, Inc.
   Jan. 2010
3. Goodman AD, et al. Lancet 2009; 373:732-38

								
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