Effective Date

Date of Origin 

04-01-2024            

06-01-2010

Ampyra®

(dalfampridine)*

Tablet

To improve walking in adult patients with multiple sclerosis (MS). This was demonstrated by an increase in walking speed

*generic equivalent available

1

Multiple Sclerosis

Multiple sclerosis (MS) is a disorder of the central nervous system (CNS) characterized by demyelization, inflammation, and degenerative changes. Most people with MS experience relapses and remissions of neurological symptoms, particularly early in the disease, and clinical events are usually associated with areas of CNS inflammation. Gradual worsening or progression, with or without subsequent acute attacks of inflammation or radiological activity, may take place early, but usually becomes more prominent over time. While traditionally viewed as a disease solely of CNS white matter, more advanced imaging techniques have demonstrated significant early and ongoing CNS gray matter damage as well.(2)

Those diagnosed with MS may have many fluctuating and disabling symptoms (including, but not limited to, fatigue, pain, bladder and bowel issues, sexual dysfunction, movement and coordination problems, visual disturbances, and cognition and emotional changes.(8) There are currently four major types of MS: clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS).(2)

Many patients with MS develop gait impairment, and some eventually require a cane or wheelchair. Gait impairment in MS can result from a multitude of issues such as spasticity, weakness, fatigue, sensory loss, visual loss, and vestibular dysfunction. Leg weakness and spasticity can result from MS lesions in the descending motor tracts of the brain and spinal cord. Ambulatory imbalance can be caused by lesions involving the cerebellar pathways. The International Symposium on Gait and balance in Multiple Sclerosis states that the causes of gait and balance dysfunction in patients with MS are multifactorial and therefore may benefit from a wide range of interventions. Evidence based recommendations from the 2nd International Symposium included balance rehabilitation, self-management, medications, functional electrical stimulation, robotics, sensory augmentation, gait training with error feedback, and fall prevention.(7)

There is ample evidence to support the benefits of ongoing treatment for the majority of people with multiple sclerosis, there may be some situations in which clinicians and their patients might consider stopping treatment. Although freedom from subsequent relapse is impossible to guarantee, treatment cessation may be considered in patients who:(2)

• Are over 60 years of age
• Have experienced a progressive disease course for five years or longer
• Have no accumulating T2 lesions or gadolinium enhancing lesions on MRI of the brain or spinal cord after a period of observation over several years.

Earlier discontinuation, particularly in patients with active disease, may lead to increased disease activity. Clinical and MRI monitoring for recurrent disease activity is clearly warranted in those patients.(2)

Efficacy

The effectiveness of Ampyra (dalfampridine) was studied in two adequate and well controlled trials involving 540 patients. Patients in these two clinical trials had a mean Kurtzke Expanded Disability Status Scale (EDSS) score of 6. Patient inclusion criteria in both trials included the ability to walk 25 feet in 8 to 45 seconds at baseline. Both trials used a responder analysis as the primary endpoint. Responders were defined as patients who achieved faster walking speeds (measured by a timed 25-foot walk in seconds) in at least three of four visits during the study period compared to their fastest speed during the off-treatment period.(1) A retrospective analysis of a previous trial indicated that treatment responders experienced a 25% improvement in walking speed compared to baseline.(3)

An FDA analysis using the entire study group (not just responders) found that neither trial demonstrated statistically significant differences in change in walking speed at visit 6 compared to baseline or average walking speed during the treatment phase of the trial. The FDA calculated that changes in walking speed would improve the 25 foot walk time for dalfampridine patients compared to placebo by 0.88 seconds and 0.5 seconds in trials MS-F203 and MS-F204, respectively. FDA analyses found that there was no significant difference between groups in either trial for the SGI score.(4) SGI is a measurement of patient perceived improvement of disease. The FDA analysis did not compare differences in walking endpoints or SGI for the responder group compared to placebo.

Evidence is lacking on how to identify patients that are likely to respond to dalfampridine without a trial of the drug. Dalfampridine is approved to improve walking speed in patients with MS and has not been shown to be effective in improving strength in other neurologic conditions (spinal cord injury, etc.). Evidence supports criteria similar to that used in Phase 3 clinical trials which includes patients diagnosed with MS who have difficulty walking as defined by a timed 25 foot walk between 8 and 45 seconds.(5) The Kurtzke Expanded Disability Status Scale (EDSS) quantifies the level of functioning that is used by health care providers diagnosing MS. The EDSS provides a total score on a scale that ranges from 0 to 10. EDSS 1.0 to 4.5 refer to patients with a high degree of ambulatory ability and subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability. An EDSS score of 7 indicates the patient is unable to walk beyond 5 meters even with aid, essentially restricted to wheelchair.(6)

Safety

Ampyra is contraindicated in:(1)

• Patients who have a history of seizures
• Patients with moderate to severe renal impairment (CrCl less than 50 mL/min) 
• Patients with a hypersensitivity to dalfampridine or 4-aminopyridine.

1

Ampyra prescribing information. Acorda Therapeutics, Inc. November 2021.

2

Multiple Sclerosis Coalition. The Use of Disease Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence. A Consensus Paper by the Multiple Sclerosis Coalition. June 2019.

3

Goodman AD, Brown TR, Cohen JA, et al. Dose comparison trial of sustained release fampridine in multiple sclerosis. Neurology 2008;71:1134-1141.

4

FDA. Medical review of fampridine. Available at:  http://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022250s000_MedR.pdf.

5

Pikoulas TE and Fuller MA.  Dalfampridine:  A Medication to Improve Walking in Patients with Multiple Sclerosis.  The Annals of Pharmacotherapy 2012;46:1010-15.

6

U.S. Department of Veterans Affair. Kurtzke Expanded Disability Status Scale. Available at: https://www.va.gov/MS/Professionals/diagnosis/Kurtzke_Expanded_Disability_Status_Scale.asp. Accessed November 2018.

7

Zackowdki KM, Cameron M, Wagner JM. Perspectives in Rehabilitation. 2^nd International Symposium on Gait and Balance in Multiple Sclerosis: interventions for gait and balance in MS. Journal of Disability and Rehabilitation. Volume 36,2014 – Issue 13. Pages 1128-1132.

8

MS international federation. About MS - Symptoms. Accessed at  MS Symptoms | Multiple Sclerosis (msif.org)

Ampyra

Dalfampridine Tab ER 12HR 10 MG

10 MG

M ; N ; O

O ; Y

Ampyra

dalfampridine tab er

10 MG

60

Tablets

30

DAYS

Ampyra

Dalfampridine Tab ER 12HR 10 MG

10 MG

Blue Partner ; Commercial ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Ampyra

dalfampridine tab er

10 MG

Blue Partner ; Commercial ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met: 

1. ONE of the following:
   1. The patient has a diagnosis of multiple sclerosis (MS) AND ALL of the following:
      1. ONE of the following:
         1. The patient will be using a disease modifying agent for the treatment of MS (e.g., Aubagio, Avonex, Bafiertam, Betaseron, Briumvi, Copaxone, Extavia, Gilenya, Glatopa, Kesimpta, Lemtrada, Mavenclad, Mayzent, Ocrevus, Plegridy, Ponvory, Rebif, Rituxan, Tascenso ODT, Tecfidera, Tysabri, Vumerity, Zeposia) in combination with the requested agent OR
         2. The patient has an intolerance, hypersensitivity, or FDA labeled contraindication to ALL disease modifying agent drug classes used for the treatment of MS (see MS disease modifying agents drug class table) AND
      2. Information has been provided that the patient has significant limitations attributable to slow ambulation AND
      3. The patient is ambulatory with a baseline (prior to therapy with the requested agent) timed 25-foot walk of 8 to 45 seconds AND
      4. Information has been provided that the patient has a current EDSS score less than 7 OR
   2. The patient has another FDA approved indication for the requested agent and route of administration AND
2. ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. The prescriber has provided information in support of using the requested agent for the patient’s age AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., neurologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent AND
5. If the requested agent is for one of the following brand agents with an available generic equivalent (listed below), then ONE of the following:
   1. The patient has an intolerance or hypersensitivity to the generic equivalent that is not expected to occur with the brand agent OR
   2. The patient has an FDA labeled contraindication to the generic equivalent that is not expected to occur with the brand agent OR
   3. The prescriber has provided information to support the use of the requested brand agent over the generic equivalent

Length of Approval: 6 months for MS and 12 months for another FDA approved diagnosis

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization Review process AND
2. ONE of the following:
   1. The patient has a diagnosis of multiple sclerosis (MS) AND ALL of the following:
      1. Information has been provided that the patient has had stabilization or improvement from baseline (before treatment with requested agent) in timed walking speed or EDSS score with the requested agent AND
      2. The patient is ambulatory AND
      3. Information has been provided that the patient has a current EDSS score of less than 7 AND
      4. ONE of the following:
         1. BOTH of the following:
            1. The patient is currently treated with a disease modifying agent for the treatment of MS (e.g., Aubagio, Avonex, Bafiertam, Betaseron, Briumvi, Copaxone, Extavia, Gilenya, Glatopa, Kesimpta, Lemtrada, Mavenclad, Mayzent, Ocrevus, Plegridy, Ponvory, Rebif, Rituxan, Tascenso ODT, Tecfidera, Tysabri, Vumerity, Zeposia) AND
            2. The patient will continue a disease modifying agent for the treatment of MS in combination with the requested agent OR
         2. The patient has an intolerance, hypersensitivity, or FDA labeled contraindication to ALL disease modifying agent drug classes used for the treatment of MS (see MS disease modifying agents drug class table) OR
   2. The patient has another FDA approved indication for the requested agent AND has had stabilization or clinical improvement with the requested agent AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., neurologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent AND
5. If the request is for one of the following brand agents with an available generic equivalent (listed below), then ONE of the following:
   1. The patient has an intolerance or hypersensitivity to the generic equivalent that is not expected to occur with the brand agent OR
   2. The patient has an FDA labeled contraindication to the generic equivalent that is not expected to occur with the brand agent OR
   3. The prescriber has provided information to support the use of the requested brand agent over the generic equivalent

Length of Approval: 12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria

QL with PA

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR          
2. ALL of the following
   1. The requested quantity (dose) exceeds the program quantity limit AND
   2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
   3. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit

Length of Approval:  Initial: 6 months for MS and 12 months for another FDA approved diagnosis. Renewal: 12 months

MS Disease Modifying Agents drug class: CD20 monoclonal antibody

MS Disease Modifying Agents drug class: CD20 monoclonal antibody

BRIUMVI*ublituximab-xiiy soln for iv infusion

MS Disease Modifying Agents drug classes: CD20 monoclonal antibody

MS Disease Modifying Agents drug classes: CD20 monoclonal antibody

KESIMPTA*Ofatumumab Soln Auto-Injector

MS Disease Modifying Agents drug classes: CD20 monoclonal antibody

OCREVUS*Ocrelizumab Soln For IV Infusion

MS Disease Modifying Agents drug classes: CD52 monoclonal antibody

MS Disease Modifying Agents drug classes: CD52 monoclonal antibody

LEMTRADA*Alemtuzumab IV Inj

MS Disease Modifying Agents drug classes: Fumarates

MS Disease Modifying Agents drug classes: Fumarates

BAFIERTAM*Monomethyl Fumarate Capsule Delayed Release

MS Disease Modifying Agents drug classes: Fumarates

TECFIDERA*Dimethyl Fumarate Capsule Delayed Release

MS Disease Modifying Agents drug classes: Fumarates

VUMERITY*Diroximel Fumarate Capsule Delayed Release

MS Disease Modifying Agents drug classes: Glatiramer

MS Disease Modifying Agents drug classes: Glatiramer

COPAXONE*Glatiramer Acetate Soln Prefilled Syringe

MS Disease Modifying Agents drug classes: Glatiramer

GLATOPA*Glatiramer Acetate Soln Prefilled Syringe

MS Disease Modifying Agents drug classes: IgG4k monoclonal antibody

MS Disease Modifying Agents drug classes: IgG4k monoclonal antibody

TYSABRI*Natalizumab for IV Inj Conc

MS Disease Modifying Agents drug classes: Interferons

MS Disease Modifying Agents drug classes: Interferons

AVONEX*Interferon Beta-

MS Disease Modifying Agents drug classes: Interferons

BETASERON*Interferon Beta-

MS Disease Modifying Agents drug classes: Interferons

EXTAVIA*Interferon Beta-

MS Disease Modifying Agents drug classes: Interferons

PLEGRIDY*Peginterferon Beta-

MS Disease Modifying Agents drug classes: Interferons

REBIF*Interferon Beta-

MS Disease Modifying Agents drug classes: Purine antimetabolite

MS Disease Modifying Agents drug classes: Purine antimetabolite

MAVENCLAD*Cladribine Tab Therapy Pack

MS Disease Modifying Agents drug classes: Pyrimidine synthesis inhibitor

MS Disease Modifying Agents drug classes: Pyrimidine synthesis inhibitor

AUBAGIO*Teriflunomide Tab

MS Disease Modifying Agents drug classes: Sphingosine 1-phosphate (SIP) receptor modulator

MS Disease Modifying Agents drug classes: Sphingosine 1-phosphate (SIP) receptor modulator

MS Disease Modifying Agents drug classes: Sphingosine 1-phosphate (SIP) receptor modulator

GILENYA*Fingolimod HCl Cap

MS Disease Modifying Agents drug classes: Sphingosine 1-phosphate (SIP) receptor modulator

MAYZENT*Siponimod Fumarate Tab

MS Disease Modifying Agents drug classes: Sphingosine 1-phosphate (SIP) receptor modulator

PONVORY*Ponesimod Tab

MS Disease Modifying Agents drug classes: Sphingosine 1-phosphate (SIP) receptor modulator

TASCENSO*fingolimod lauryl sulfate tablet disintegrating

MS Disease Modifying Agents drug classes: Sphingosine 1-phosphate (SIP) receptor modulator

ZEPOSIA*Ozanimod Cap Pack