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New ALS Drug Approved

On 5/5/17, the U.S. Food and Drug Administration approved Radicava (edaravone) to treat patients with amyotrophic lateral sclerosis (ALS).(www.fda.gov)

 

Radicava is an intravenous infusion given by a health care professional. It is administered with an initial treatment cycle of daily dosing for 14 days, followed by a 14-day drug-free period. Subsequent monthly treatment cycles consist of dosing on 10 of 14 days, followed by 14 days drug-free. The infusions take 60 minutes.

 

The efficacy of edaravone for the treatment of ALS was demonstrated in a six-month clinical trial conducted in Japan. In the trial, 137 participants were randomized to receive edaravone or placebo. At Week 24, individuals receiving edaravone declined about 1/3 less on a clinical assessment of daily functioning compared to those receiving a placebo. There was no change in breathing function in the treatment or placebo group.

 

The most common adverse reactions reported by clinical trial participants receiving edaravone were bruising and gait disturbance. Patients in the study received daily venous punctures for the infusions, hence the bruising.

 

Radicava is also associated with serious risks that require immediate medical care, such as hives, swelling, or shortness of breath, and allergic reactions to sodium bisulfite, an ingredient in the drug. Sodium bisulfite may cause anaphylactic symptoms that can be life-threatening in people with sulfite sensitivity.

 

Patients in the study had:

  • ALS for 2 years or less with independent living status
  • At least 2 affected body regions (arm, leg, bulbar or trunk)
  • Normal breathing (FVC > 80%) at time of entry
  • Progressive Disease (usually at least moderately progressive)
  • ALSFRS-R score > 2 on each sub-item

Exclusion criteria:

  • ALSFRS-R < 3 on any breathing sub-item, spinal surgery after onset

The ALSFRS-R is a functional rating scale that measures bulbar function (speech, salivation, and swallowing), fine motor function (handwriting, cutting food/handling utensils, and dressing and hygiene), gross motor function (walking, climbing stairs, and turning in bed), and breathing (shortness of breath, breathing when lying flat, and use of BiPAP). There are 3 items per section graded 0-4 with 4 being normal. The maximum score is 48.

 

Details about the Results of the Study

 

Edaravone use was associated with a slower decline in the ALSFRS-R

  • Edaravone group declined 2.49 points less than placebo (-5.01 vs -7.50) over 6 months
    • Of note, clinicians and researchers previously surveyed rated a 20-25% change in slope “somewhat clinically meaningful” (≥ 4 on a 1-7 scale of effect), and this benefit was about 30%.
  • Study patients averaged a relatively rapid rate of decline
    • 1.35 points/month for placebo group (usual is about 0.6 points/month in the first yr and 0.34 points/month in the second year)
    • 0.90 points/month for edaravone group

A previous study in which patients had disease for less than 3 years showed no significant benefit.

 

The drug became available in August 2017.

 

The company is setting up services with regional infusion companies and coordinating with insurers. Patients can contact them at www.radicava.com

 

We anticipate that patients will need a port (indwelling catheter) that will complicate start-up and increase the long-term risks including significant infection.

 

There is no data on how long patients should be treated, but insurers are generally approving it for 6 months and then require re-approval.  The drug is only approved for ALS and not PLS or other neurologic conditions. The cost of the drug is about $145,000 per year. The drug company has a program to assist financially for commercial insurance but not medicare or Medicaid.

 

So far, insurers appear to be covering treatment only if patients meet study criteria.

 

UPMC Health Plan (preliminary)

 

Initial Authorization Criteria:

  • Must be prescribed by a neurologist
  • Must have a diagnosis of definite or probable amyotrophic lateral sclerosis (ALS)
  • Must have disease duration of less than 2 years
  • Must have a forced vital capacity (FVC) ≥ 80%. Chart documentation of FVC is required
  • Must not have a tracheostomy, artificial respirator with intubation or receive tube feedings

If the above criteria are met, edaravone (Radicava) is approved for 6 months.

 

Aetna Policy http://www.aetna.com/cpb/medical/data/900_999/0918.html

PRECERTIFICATION REQUIRED*

 

Site of Care Utilization Management Policy applies.  For information on site of service for edaravone, see Utilization Management Policy on Site of Care for Specialty Drug Infusions.

 

Aetna considers edaravone (Radicava) medically necessary for the treatment of individuals with amyotrophic lateral sclerosis (ALS) when all the following criteria are met:

  • Functionality retained most activities of daily living (defined as scores of 2 points or better on each individual item of the ALS Functional Rating Scale-Revised (ALSFRS-R; see Appendix)); and
  • Normal respiratory function (defined as percent-predicted forced vital capacity values of [%FVC] greater than or equal to 80%); and
  • Definite or probable ALS based on El Escorial revised criteria (see Appendix); and
  • Disease duration of 2 years or less

Continuation Criteria:

Aetna considers continued use of edaravone medically necessary when the following criteria are met:

  • There is documentation indicating that edaravone use has slowed the progression of ALS; and
  • Overall function should be improved/superior relative to that projected for the natural course of ALS.

* Precertification of edaravone is required of all Aetna participating providers and members in applicable plan designs.  For precertification of edaravone, call (866) 503-0857, or fax (866) 267-3277. 

 

United Healthcare

 

Radicava (edaravone) is proven and medically necessary for: 

  • The treatment of amyotrophic lateral sclerosis (ALS) in patients who meet ALL of the following criteria:
    • For initial therapy, ALL of the following: (1) Submission of medical records (e.g., chart notes, previous medical history, diagnostic testing including: imaging, nerve conduction studies, laboratory values) to support ONE of the following:
      • Diagnosis of “definite” or “probable” ALS per the revised EL Escorial and Airlie House diagnostic criteria, and prescribed by a neurologist with expertise in the diagnosis of ALS
      • Diagnosis of “definite” or “probable” ALS per the revised EL Escorial and Airlie House diagnostic criteria, and prescribed by a physician in consultation with a neurologist with expertise in the diagnosis of ALS;
      • AND (2) Submission of the most recent ALS Functional Rating Scale-Revised (ALSFRS-R) score confirming that the patient has scores ≥ 2 in ALL items of the ALSFRS-R criteria at the start of treatment;
      • AND (3) Submission of medical records (e.g., chart notes, laboratory values) confirming that the patient has a % forced vital capacity (%FVC) ≥ 80% at the start of treatment; AND Commercial Policy
      • (4) Radicava dosing for ALS is in accordance with the United States Food and Drug Administration approved labeling;
      • AND (5) Initial authorization will be for no more than 6 cycles (64 doses over 168 days).
    • For continuation therapy, ALL of the following: (1) ONE of the following: (a) Diagnosis of “definite” or “probable” ALS per the revised EL Escorial and Airlie House diagnostic criteria, and prescribed by a neurologist with expertise in the diagnosis of ALS (b) Diagnosis of “definite” or “probable” ALS per the revised EL Escorial and Airlie House diagnostic criteria, and prescribed by a physician in consultation with a neurologist with expertise in the diagnosis of ALS; AND (2) Patient is currently receiving Radicava therapy; AND (3) Patient is NOT dependent on invasive ventilation or tracheostomy; AND (4) Radicava dosing for ALS is in accordance with the United States Food and Drug Administration approved labeling; AND (5) Authorization will be for no more than 6 cycles (60 doses over 168 days).

Medicare approval is based on Part D prescription drug coverage. Depending on the particular plan, there may be a 20% copay for patients (about $30,000 per year). Such patients may receive the drug at home from an infusion company. For Medicare patients who do not have Part D coverage, the drug may be provided at infusion centers under Part B coverage. Such patients may also be subjected to a copay.

 

The proposed guidelines for PA Medicaid are very similar to the UPMC Health plan authorization criteria found above.

 

Live Like Lou Center for ALS Research at the University of Pittsburgh Brain Institute. 

The Live-Like-Lou Center for ALS Research was created in February, 2015 following a $2.5 million dollar pledge by LiveLikeLou.org via the Pittsburgh Foundation. Live Like Lou was founded by Neil and Suzanne Alexander.  The University of Pittsburgh matched the contribution as part of an effort to raise $10 million dollars for this new research center.  The former University of Pittsburgh Center for ALS Research has been folded into the Live Like Lou Center for ALS Research, and the MDA/ALS Center will be a clinical arm of this extensive research effort. 


New Gene Discoveries.The most important relatively recent description of a large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 on chromosome 9p was an exciting development in ALS research. This mutation is associated with up to 40% of cases of familial ALS (fALS). In some families, children developed onset of symptoms 7 years earlier than their parents. Either frontotemporal dementia (FTD) or motor neuron disease (MND) occurs in affected families. Some patients had psychosis with prominent delusions and hallucinations. It is still not certain as to how the C9ORF72 mutation causes motor neuron degeneration. There have been numerous reports of this gene and its presence in various populations. In the US, it is seen in about 3% of patients with sporadic ALS.

C9ORF72 and SOD1 mutations account for about half of all cases of familial ALS.


However, there are now more than 30 genetic causes of ALS. They are shown in the table below.


AR= autosomal recessive

Other reported mutations occur in these genes: DAO, DCTN1, NEFH, PRPH, SQSTM1, TAF15, SPAST, ELP3, LMNB1

See http://alsod.iop.kcl.ac.uk/ for details.

What else is new in ALS? We now know that about 13% of patients with ALS have other “atypical features” suggesting involvement of other parts of the nervous system and explaining some of these unusual occurrences.  These abnormalities could include problems with eye movement, coordination, tremor, slow limb movement, rigidity, excessive sweating, loss of taste and/or smell.  Emotional lability (pseudobulbar affect) is more common in this group of patients as well.  (McCluskey L et al.  ALS-Plus syndrome: non-pyramidal features in a large ALS cohort.  J Neurol Sci 2014;345:118-124). 

Urinary disturbances may be more common than previously thought in patients with ALS.  In one study, up to 40% of patients with ALS had symptomatic urinary disorders.  Although some of these problems may be related to ALS, the use of medications could also predispose patients.  Medications such as those used to treat spasticity or depression can lead to urinary symptoms.  (Lopes de Carvalho ML et al.  Urinary disorders in amyotrophic lateral sclerosis.  Amyotroph Lateral Scler 2011;12:352-355.  Nübling GS et al.  Increased prevalence of bladder and intestinal dysfunction in amyotrophic lateral sclerosis.  Amyotroph Lateral Scler Frontotemporal Degener 2014;15:174-179). 

 

Deep venous thrombosis (blood clots) in the legs leading to pulmonary embolism or clots in the lungs has been a concern in patients with ALS.  In one study, 4 of 50 patients developed blood clots in the legs over a year.  One of these developed pulmonary emboli.   Patients at the greatest risk appear to have onset of disease in the legs and being wheelchair bound.  Unfortunately,  we do not know how to prevent blood clots safely in ALS patients and whether or not patients should be routinely screened for blood clots.  (Glad M et al.  Venous thromboembolism in amyotrophic lateral sclerosis.  Neurology 2014;82:1674-1677).