Effective Date

Date of Origin 

07-01-2024            

10-01-2023

Skyclarys®

(omaveloxolone)

Capsule

Treatment of Friedreich's ataxia in adults and adolescents aged 16 years and older

1

Friedreich Ataxia

Friedreich ataxia (FA, FRDA) is a progressive autosomal recessive genetic neurodegenerative disorder affecting approximately 5,000 patients in the United States and 22,000 patients globally.(4,5) FA is caused by a biallelic trinucleotide (GAA) repeat expansion in the first intron of the FXN gene, which impairs transcription and significantly reduces the amount of functional frataxin protein. The pathological consequences of frataxin deficiency include disruption of iron–sulfur cluster biosynthesis, cellular iron dysregulation, mitochondrial dysfunction, and increased sensitivity to oxidative stress leading to the clinical features of FA.(2,3,4,5)

Ataxia is the most common clinical feature in FA, reflecting both proprioceptive loss and cerebellar disease. Patients can also develop spasticity, visual and hearing loss, and non‐neurological features such as cardiomyopathy, diabetes, and scoliosis. In most patients, symptoms begin between 5 and 15 years of age, and patients lose the ability to ambulate by their mid‐20s. FA shortens life span, most often through consequences of cardiomyopathy; average age at death is 37 years.(4,5)

Genetic testing for the triplet repeat expansions in the first intron of the frataxin (FXN) gene that cause Friedreich ataxia should be performed in all patients with progressive cerebellar ataxia and autosomal recessive inheritance.(2,3,4,5) In individuals who are ambulant, clinical management guidelines recommend regular monitoring of ambulation and contributing physical and non-physical factors for mobility decline (e.g., balance, strength, lower limb spasticity, fear of falling) at least once per year. For non-ambulant individuals, regular monitoring of mobility (including ability to transfer) and contributing factors for mobility decline (e.g., balance, strength, lower limb spasticity, environmental set-up) is recommended at least once per year.(6) 

Until omaveloxolone was approved by the FDA for treatment of FA, there was no specific disease-modifying therapy available. The management of patients with this disorder requires a multidisciplinary team of special services. An occupational and physical therapy program should be initiated early. Periodic evaluation of cardiac function is required. Similarly, patients should be monitored for the development of dysphagia, scoliosis, vision loss, hearing loss, bladder dysfunction, sleep apnea, and diabetes mellitus.(4,5)

Efficacy

Omaveloxolone is an activator of the Nuclear factor-like (Nrf2) pathway, which is involved in the cellular response to oxidative stress.(1) Treatment with omaveloxolone in vitro restores mitochondrial function in fibroblasts from Friedreich ataxia patients and in neurons from multiple mouse models.(4,5)

In a larger international randomized trial, 103 patients with Friedreich ataxia (median age, 21 to 22 years; mean disease duration, approximately 4.5 years) were randomly assigned to omaveloxolone 150 mg daily or placebo for 48 weeks. Efficacy data were presented for 82 patients (80%) who received 48 weeks of treatment and had completed primary outcome measurements on the mFARs. Among these patients, mFARS scores improved by 1.55 points in the omaveloxolone group and worsened by 0.85 points in the placebo group (mean difference between groups -2.4 points, 95% CI -4.3 to -0.5). Adverse effects that occurred more commonly with omaveloxolone than placebo included elevated aminotransferase levels (37 versus 2%; no cases of clinical liver injury), headache (37 versus 25%), and nausea (33 versus 14%).(1)

Although the trial had limitations and the effect size was relatively modest, Friedreich ataxia is a slowly progressive disease, and small differences in functional progression over one to two years could translate to meaningful differences over the course of the disease.(5)

1

Skyclarys prescribing information. Reata Pharmaceuticals, Inc. February 2023.

2

Rummey C, Corben LA, Delatycki M, et al. Natural History of Friedreich Ataxia. Neurology. 2022 Oct;99(14):e1499-e1510.

3

Pandolfo M. Friedreich Ataxia. Arch Neurol. 2008 Oct;65(10):1296-1303.

4

Lynch DR, Chin MP, Delatycki MB, et al. Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study). Ann Neurol. 2021 Feb;89(2):212-225.

5

Opal P, Zoghbi H, et al. Friedreich Ataxia. UpToDate. Last updated November 2023. Literature review current through December 2023.

6

Corben LA, Collins V, Milne S, et al. Clinical Management Guidelines for Friedreich Ataxia: Best Practice in Rare Diseases. Orphanet J Rare Dis. 2022;17:415.

Skyclarys

omaveloxolone cap

50 MG

M ; N ; O ; Y

N

Skyclarys

omaveloxolone cap

50 MG

90

Capsules

30

DAYS

Skyclarys

omaveloxolone cap

50 MG

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

Skyclarys

omaveloxolone cap

50 MG

Blue Partner ; Commercial ; GenPlus ; 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 requested agent is eligible for continuation of therapy AND ONE of the following:

1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
3. ALL of the following:
   1. The patient has a diagnosis of Friedreich ataxia (FA, FRDA) with genetic analysis confirming mutation in the frataxin (FXN) gene AND
   2. If the patient has an FDA labeled indication, then ONE of the following:
      1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
      2. There is support for using the requested agent for the patient’s age for the requested indication AND
   3. The prescriber has assessed baseline status (prior to therapy with the requested agent) of the patient's symptoms (e.g., mobility, balance, strength, lower limb spasticity) AND
4. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., cardiologist, geneticist, neurologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent 

Length of Approval:  12 months

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

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 process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient has had improvements or stabilization with the requested agent (e.g., mobility, balance, strength, lower limb spasticity) AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., cardiologist, geneticist, 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

Length of Approval:  12 months

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

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 OR
3. ALL of the following:
   1. The requested quantity (dose) exceeds the program quantity limit AND
   2. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
   3. There is support of therapy with a higher dose for the requested indication

Length of Approval:  up to 12 months