2.3.R1 Recommendation

Omaveloxolone treatment for individuals with FRDA aged 16 years and over

Published June 10, 2022

Strength of recommendation:
Strong for intervention
Level of evidence:
Moderate
How the strength and level of evidence are graded

What the strength of a recommendation means

The strength of a recommendation reflects the extent to which a guideline panel is confident that desirable effects of an intervention outweigh undesirable effects, or vice versa, across the range of patients for whom the recommendation is intended.

Strong for (↑↑) or against (↓↓) intervention
For patients: Most individuals in this situation would want the recommended course of action and only a small proportion would not.
For clinicians: Most individuals should receive the recommended course of action.

Conditional for (↑) or against (↓) intervention
For patients: The majority of individuals in this situation would want the suggested course of action, but many would not.
For clinicians: Recognize that different choices will be appropriate for different patients, and that you must help each patient arrive at a management decision consistent with her or his values and preferences.

Neither intervention nor comparison (—)
The panel did not recommend for or against the intervention.

Source: GRADE Handbook, section 6.1, Table 6.1 (GRADE uses “weak” and “conditional” interchangeably).

For the rating of the strength of the recommendation, in addition to evidence from studies in FRDA, evidence from like conditions, clinical experience and expert consensus are taken into account when published evidence is not available.

The level of evidence is based on published evidence from studies in FRDA. If there is no published evidence in FRDA, evidence from other like conditions or clinical expertise may have been used to make the recommendation – this is graded as ‘very low’ or in some cases ‘low’ level evidence. See the table below for an explanation of the symbols used to grade recommendations.

Strength of recommendation Symbol Level of evidence Symbol
Strong for intervention ↑↑ High ⨁⨁⨁⨁
Conditional for intervention ↑ Moderate ⨁⨁⨁◯
Neither intervention nor comparison — Low ⨁⨁◯◯
Conditional against intervention ↓ Very low ⨁◯◯◯
Strong against intervention ↓↓
Chapter PDF

We recommend the use of 150mg daily of omaveloxolone administered according to regulatory guidelines over no omaveloxolone for providing neurological benefit for individuals with Friedreich ataxia aged 16 years and over.

Question

Should 150mg daily of omaveloxolone vs. none be used for providing neurological benefit for individuals with Friedreich ataxia aged 16 years and over?

Justification

Given the landscape of the FRDA disease, the known trajectory of ongoing decline in neurological function, the absence of any other approved drug treatments to benefit neurological function and the low rate of adverse effects recorded in the RCTs, we believe individuals with FRDA aged 16 years and over residing in jurisdictions where regulatory approval has been granted would likely gain benefit from treatment with omaveloxolone. The current evidence therefore supports a strong recommendation for its use in individuals with FRDA aged 16 years and over when administered according to labeling guidelines.
As is the case for any drug treatment, clinical experience indicates that individuals’ perceptions of the magnitude of the desirable effects of omaveloxolone may vary according to factors such as prior (to treatment) expectations of the level of effect and the individual’s stage of disease (whether in early stages or advanced). Ongoing clinical follow-up of patients suggests the beneficial effects are maintained beyond the duration of the studies. Early clinical experience is reinforcing the need for monitoring of both liver function enzymes and lipids and suggests a higher incidence of increased cholesterol levels which may require intervention with statin therapy.

Subgroup consideration

Omaveloxolone is currently only approved for individuals aged 16 years and over. Efficacy of treatment for individuals aged <16 years and those with lower mobility and reduced cardiac function is unclear at this stage, but there is no obvious reason that omaveloxolone would not be beneficial for other groups of individuals with FRDA.
Clinicians need to be aware of the drug regulatory situation and labeling guidance in their jurisdiction. Regulatory approval for the use of omaveloxolone for FRDA (in those aged 16 years and over) has so far only been granted in the USA and the EU.

Evidence to recommendation table (PDF)

Part of 2.3 Therapies approved or under investigation

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Disclaimer, intended use and funding

Disclaimer
The Clinical Management Guidelines for Friedreich ataxia (‘Guidelines’) are protected by copyright owned by the authors who contributed to their development or said authors’ assignees.

These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.

Guidelines users must seek out the most recent information that might supersede the diagnostic and treatment recommendations contained within these Guidelines and consider local variations in clinical settings, funding and resources that may impact on the implementation of the recommendations set out in these Guidelines.

The authors of these Guidelines disclaim all liability for the accuracy or completeness of the Guidelines, and disclaim all warranties, express or implied to their incorrect use.

Intended Use
These Guidelines are made available as general information only and do not constitute medical advice. These Guidelines are intended to assist qualified healthcare professionals make informed treatment decisions about the care of individuals with Friedreich ataxia. They are not intended as a sole source of guidance in managing issues related to Friedreich ataxia. Rather, they are designed to assist clinicians by providing an evidence-based framework for decision-making.

These Guidelines are not intended to replace clinical judgment and other approaches to diagnosing and managing problems associated with Friedreich ataxia which may be appropriate in specific circumstances. Ultimately, healthcare professionals must make their own treatment decisions on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge and expertise.
Guidelines users must not edit or modify the Guidelines in any way – including removing any branding, acknowledgement, authorship or copyright notice.

Funding
The authors of this document gratefully acknowledge the support of the Friedreich Ataxia Research Alliance (FARA). The views and opinions expressed in the Guidelines are solely those of the authors and do not necessarily reflect the official policy or position of FARA.