US FDA Grants Expanded Approval of ELEVIDYS Gene Therapy for DMD Patients Ages 4 and Above

FA: Idebenone Clinical Trials

Overall, idebenone has been shown to be safe and well-tolerated in a number of phase 1, 2 and 3 human clinical trials dating back to 1999. The most common side effects are mild to moderate gastrointestinal issues such as diarrhea, nausea and indigestion. Early trials at low doses first demonstrated the potential for idebenone to reduce FA-associated cardiomyopathy (heart muscle abnormality).

Over the past decade, the drug has consistently demonstrated in a number of trials its ability to improve heart structure by reducing FA-related abnormal thickening (cardiac hypertrophy) of tissues in particular areas of the heart. Specific measurements used to determine such improvement include interventricular septal wall thickness (SWT), left ventricular posterior wall thickness (PWT) and left ventricular mass index (LVMI).

In addition, results from some trials have suggested a reduction in cardiac strain, as indicated by a measurement called shortening fraction, which measures performance of the heart by assessing the change in diameter of the left ventricle between the contracted and relaxed states. The decrease in cardiac strain was associated with improved heart function.

A number of studies found that cardiac benefits varied significantly among individuals. Most indications in earlier trials of idebenone’s potential to improve or stabilize neurological dysfunction found no benefit. More recent trials, however, particularly those in which higher doses of the drug have been tested, have demonstrated improved neurological function.

  • ADL: Activities of Daily Living. This ratings system assesses the ability of an individual to perform day-to-day activities such as dressing, eating, moving, toileting, taking medication, using a telephone or other technology, and others.
  • CAGRS: Cooperative Ataxia Group Rating Scale. This scale measures neurological function/dysfunction.
  • FARS: Friedreich’s Ataxia Rating Scale. Another measurement of neurological function/dysfunction.
  • ICARS: International Cooperative Ataxia Rating Scale. This measurement of neurological function/dysfunction currently is the preferred scale.
  • Catena/Sovrima: Catena is the brand name for idebenone in Canada and the United States. Sovrima is the brand name for the drug in Europe.

2010 — Spain

Trial: Combined Therapy with Idebenone and Deferiprone in Patients with Friedreich’s Ataxia

Objective and Description: Aims of this study included evaluation of the effects of combined idebenone-deferiprone therapy on neurological signs and heart function.

Twenty individuals with FA were treated with idebenone (20 mg/kg/day) and the iron chelator deferiprone (20 mg/kg/day) for 11 months.


  • No significant differences were observed in total ICARS scores when comparing status at the beginning of the study (baseline) and the end of the study in the whole group of patients. However, differences were noted in specific ICARS categories. Namely, posture and gait scores worsened, while fine-motor function improved significantly.
  • Heart-imaging (echocardiography) data showed a significant reduction in abnormal thickness of a part of the heart called the septum.
  • MRI testing showed statistically significant reduction, between baseline and after 11 months of therapy, of iron deposits in a part of the brain called the dentate nucleus.
  • Results suggest combined idebenone-deferiprone therapy in people with FA confers an overall stabilizing effect in neurological dysfunction, and significant improvement in heart hypertrophy (abnormal enlargement) and iron levels in the brain.
  • The therapy was well-tolerated with mild side effects. Noted risks include neutropenia (an abnormal decrease in levels of a particular type of white blood cell) and reduction of blood iron levels.

2010 — Europe

Trial: Mitochondrial Protection with Idebenone in Cardiac or Neurological Outcome Study (MICONOS)

Objective and Description: This study was designed to evaluate the safety and efficacy of three different doses of Catena/Sovrima versus that of placebo.

A total of 232 individuals (primarily adults) with FA received the low (180/360, depending on body weight, mg/day), medium (450/900 mg/day) or high dose (1,350/2,250 mg/day), or placebo, every day for 12 months.


  • The MICONOS trial missed its primary endpoint, which was mean change in ICARS score as measured at the beginning, and again at the end, of the study. No significant difference was noted between those receiving idebenone and those receiving placebo.
  • In addition, no difference was noted between the active and placebo groups in measurements of key anatomical and functional cardiac parameters.
  • Data still is being culled from long-term extension studies following this trial. The MICONOS extension was listed as “ongoing, but not recruiting patients” as of Aug. 20, 2010 on

2010 — Canada

Trial: Intermediate-Dose Idebenone and Quality of Life in Friedreich’s Ataxia

Objective and Description:This phase 3 observational study examined the effect of intermediate-dose idebenone (20 mg/kg/day) on quality of life and neurologic function measures.

Seven patients with FA, ages 13 years to 18 years (four male and three female) were administered treatment for a period of one year.


  • Patients were assessed using the Pediatric Quality of Life Inventory, the ICARS, and an Activities of Daily Living Scale, both before starting idebenone and after one year of therapy.
  • Physical scores on the Pediatric Quality of Life Inventory were universally worse after one year, and correlated with decreased activities of daily living scores.
  • Despite worsening physical scores, there was a trend toward improved total, emotional, social and school components of quality of life scores.
  • There was no statistically significant change in Pediatric Quality of Life Inventory scores from the beginning to the end of the study.
  • Functional ability, as measured by activities of daily living scores, appeared to have the most influence on the perception of physical quality of life.

2009 — United States

Trial: Idebenone Effects on Neurological ICARS Assessments study (IONIA)

Objective and Description: This phase 3 study compared the safety, tolerability and efficacy, of two different doses of Catena versus placebo. The low dose was 450 or 900 mg/day, depending on body weight. The high dose was 1,350/2,250 mg/day.

Seventy individuals with FA, ages 8 years through 18 years, who still were ambulatory, were assigned to one of three treatment groups: low-dose idebenone, high-dose idebenone or placebo. Doses were administered daily over a period of six months.


  • The IONIA study missed its primary outcome measure, which was the mean change in ICARS scores taken at baseline and again after 24 weeks.
  • Patients who received idebenone improved by 2.5 points on mean ICARS score compared with baseline, while patients in the placebo group improved by 1.3 points. Patients who took idebenone also improved by 1.6 points on the FARS, while patients taking placebo declined by 0.6 points.
  • For both end points, the difference between the idebenone and placebo groups was not statistically significant.

(It should be noted that the IONIA study was designed using parameters from the prior U.S. phase 2 NICOSIA study. Compared to the placebo group, improvement in both IONIA groups taking Catena measured only about half as much as had those in the prior U.S. Phase 2 NICOSIA study. It was observed that those in the IONIA placebo group did not deteriorate to the extent expected from the NICOSIA study or as described in literature, possibly skewing the results.)

2009 — Italy

Trial: Low-Dose Idebenone Treatment in Friedreich’s Ataxia with and without Cardiac Hypertrophy

Objective and Description: This study was a retrospective analysis of 35 individuals with FA (20 with cardiac hypertrophy, 15 without), who were treated with idebenone 5 mg/kg/day for up to 60 months.


  • The heart’s responsiveness to treatment with idebenone varied greatly among trial participants. The researchers observed no correlation with sex, age, size of GAA repeat expansion, or severity of cardiomyopathy prior to the study.
  • In those who had cardiac hypertrophy at the beginning of the study, no changes in heart tissue thickness measurements were noted. In those who began the study without cardiac hypertrophy, measurements showed the thickening of particular areas of heart tissue consistent with cardiac hypertrophy.
  • No neurological benefits were noted. There was significant progression of neurological dysfunction over the time period studied.

2008 — Switzerland, United States

Trial: NIH Collaboration with Santhera in Ataxia (NICOSIA) trial

Objective and Description: This phase 2 study aimed to establish safety data and effect on neurological symptoms of high-dose idebenone in young individuals with FA.

The trial enrolled 48 people with FA, with 12 in each of three dose groups, and 12 in a placebo group.


  • Results showed that idebenone was safe and well-tolerated, and that it produced a positive effect as measured by ICARS as well as with activities of daily living scales.
  • Analysis revealed that those treated with the drug showed a trend toward dose-proportional improvement in neurological function, as measured by ICARS, after a six-month course of treatment.

2008 — Spain

Trial: Idebenone Treatment in Pediatric and Adult Patients with Friedreich’s Ataxia: Long-Term Follow-Up

Objective and Description: The aim of this study was to assess the effectiveness of long-term treatment with idebenone in people with FA. 

Ten children with FA (ages 8 years to 18 years) and 14 adults (ages 18 years to 46 years) with genetic diagnosis of FA were treated with idebenone (5-20 mg/kg/day) for a period of three years to five years.


  • Neurological status was evaluated using ICARS, and heart health was tested using a type of heart-imaging test called an echocardiogram.
  • ICARS scores showed initial improvement in children, with stabilization over the long term. In adults, scores showed significant worsening of neurological function.
  • Analysis also showed the treatment prevented progression of cardiomyopathy in both children and adult patients.
  • The authors suggested that, based on these results, effectiveness of idebenone therapy may depend on the age at which it’s initiated.

2007 — United States

Trial: Neurological Effects of High-Dose Idebenone in Patients with Friedreich’s Ataxia: A Randomized, Placebo-Controlled Trial

Objective and Description: This trial enrolled 48 people with FA between the ages of 9 years and 17 years.

Each was randomly placed into a placebo or one of three idebenone treatment groups. Those in the treatment groups received fixed daily doses of idebenone, (180/360 mg/day, 450/900 mg/day or 1,350/2,250 mg/day, depending on body weight) over a period of six months.


  • Treatment with doses of idebenone was generally well tolerated at all doses up to 2,250 mg/day. At higher doses the treatment was associated with a trend toward improvement (but not a significant difference) in neurological function and activities of daily living in patients with FA.
    The degree of improvement correlated with the dose of idebenone, suggesting that higher doses may be necessary to have a beneficial effect on neurological function.
  • Overall, analysis showed no significant difference in FARS, ICARS or ADL scores. In one experiment, however, in which patients who required wheelchair assistance were excluded, a significant improvement in ICARS scores and apparent dose-related response in ICARS, FARS and ADL scores was observed.

2007 — France

Trial: Neurological, Cardiological and Oculomotor Progression in 104 Patients with Friedreich’s Ataxia During Long-Term Follow-Up

Objective and Description: Researchers followed 104 people with FA every six months over a period averaging five years, using a standardized measurement protocol.

No trial participants were receiving antioxidant therapy prior to the beginning of the study. Eighty-eight were treated with idebenone at 5 mg/kg per day; 16 declined the treatment.


  • The neurological condition of FA patients deteriorated slowly over time, even with idebenone treatment. It was suggested that overall progression may have been underestimated ICARS scores, which plateaued in those patients with long disease courses. Although cardiac hypertrophy decreased under treatment, cardiac function did not improve.
  • Specifically, ICARS scores worsened during follow-up, regardless of whether the patients received idebenone. Worsening of the ICARS scores increased faster in patients with onset before age 15 years compared with the others.
  • Oculomotor (eye movement) function deteriorated slightly.

2006 — France

Trial: Expanding View of Phenotype and Oxidative Stress in Friedreich’s Ataxia Patients with and without Idebenone

Objective and Description: The goal of this study was to examine neurological effects of idebenone. Investigators also looked at the drug’s effect on blood levels of malondiadehyde (MDA), an organic compound known to indicate oxidative stress.

Twenty adults with FA were treated with 5 mg/kg/day to 10 mg/kg/day idebenone over periods varying from several months up to three and a half years.


  • Overall ICARS scores did not improve, but improvements in neurological function were seen in speech, increased hand dexterity and decreased fatigue.
  • Treatment with idebenone was positively correlated with an increase in blood levels of MDA.

2003 — Belgium

Trial: Idebenone Treatment in Friedreich’s Ataxia: Neurological, Cardiac and Biochemical Monitoring

Objective and Description: Researchers studied eight people with FA, between the ages of 9 years and 27 years, with cardiomyopathy.

All trial participants received 5 mg/kg/day in three doses (maximum 300 mg/day) for one year.


  • Evaluations of ataxia, cardiac structure and function, biochemical markers and adverse effects were conducted at the beginning of the study and after four, eight and 12 months of treatment.
  • As indicated by CAGRS scores, idebenone did not halt the progression of ataxia.
  • At the end of therapy, cardiac ultrasound demonstrated significant reduction of cardiac hypertrophy in six of eight patients. Analysis showed this reduction of hypertrophy was preceded by an early and linear improvement in cardiac function.

2003 — Italy

Trial: Idebenone Treatment in Friedreich Patients: One-Year-Long Randomized Placebo-Controlled Trial

Objective and Description: The goal of this trial was to determine cardiac and neurological effects of idebenone in people with FA.

Twenty-nine study participants with FA, ages 21 years to 32 years, were placed into idebenone and placebo groups (14 and 15, respectively. Each received either idebenone (5 mg/kg/day) or placebo three times daily.


  • No serious side effects were associated with idebenone treatment.
  • Effects of idebenone on the heart varied greatly among the trial participants.
  • Analysis revealed significant reductions in measurements indicative of cardiac hypertrophy in the treatment group; these results were not observed in the placebo group. No improvement was noted in various other heart ultrasound measures or in neurologic condition.
  • Although the overall cardiac changes were moderate, the findings suggested idebenone may reduce cardiac hypertrophy in people with FA.

2002 — France

Trial: Idebenone and Reduced Cardiac Hypertrophy in Friedreich’s Ataxia

Objective and Description: The aim of this trial was to assess the efficiency of idebenone on cardiac hypertrophy in FA.

Idebenone was given orally (5 mg/kg/day) to 38 trial participants with FA, ages 4 years to 22 years (20 males, 18 females).


  • After six months of treatment, cardiac ultrasound indicated a reduction in parameters indicative of cardiac hypertrophy in approximately half of the trial participants. Cardiac hypertrophy was largely stabilized in the other half and in none of them did the hypertrophy significantly increase over the six-month trial period.
  • No correlation was found between responsiveness to idebenone and age, sex, initial ultrasound indices, or the number of GAA repeats in the frataxin gene.

2002 — Spain

Trial: Friedreich’s Ataxia: Idebenone Treatment in Early-Stage Patients

Objective and Description: The aim of this study was to assess the effects of idebenone treatment in cardiac health and neurological function in people with FA.

Nine trial participants with FA, ages 11 years to 19 years, were treated with idebenone (5 mg/kg/day) for one year.


  • No changes were noted in cardiac measurements taken prior to and after the study.
  • Concentrations of idebenone in trial participants’ blood showed significant positive correlation with ICARS scores before and 12 months after the start of the study.
  • Significant improvement was observed in ICARS scores measured three months after start of treatment.
  • Notable improvement in part of the brain called the cerebellum (responsible for motor function and balance) was observed in patients with mild cases of the disease after three months of therapy. Treatment at early stages appeared to reduce cerebellar degeneration.

2001 — Germany

Trial: Idebenone in Patients with Friedreich’s Ataxia

Objective and Description: In this study, researchers examined effects of idebenone on cardiac function.

Nine FA patients, ages 9 years to 54 years, received either 360 mg/kg/day of idebenone or placebo for a period of one and a half months.


  • MRI results showed impairment in skeletal muscle of all FA patients, which idebenone did not help. No positive benefits were noted, and heart imaging tests (echocardiograms) failed to confirm results from a preliminary study suggesting improvement of FA-associated cardiomyopathy with idebenone.
  • The study authors noted that the duration of treatment probably was too short to make a valid conclusion.

2000 — Germany, United States

Trial: Oxidative Stress in Patients with Friedreich’s Ataxia

Objective and Description: The aim of this study was to determine the effects of idebenone on a particular biochemical indicator “biomarker” for oxidative stress.

Eight people with FA were treated with idebenone (5 mg/kg/day) for a period of two months.


  • The small molecule biomarker, 80H2’dG 8-hydroxy-2’ –deoxyguanosine, measured in urine output, decreased by 20 percent with idebenone treatment — a possible indicator of reduced oxidative stress.

1999 — France

Trial: Effect of Idebenone on Cardiomyopathy in Friedreich’s Ataxia: A Preliminary Study

Objective and Description: Three individuals, ages 11 years, 19 years and 21 years, received 5 mg/kg/day of idebenone for a period of four to nine months.


  • Results showed a reduction of abnormal thickening in measurements of three areas of the heart.
  • Note: One individual who continued the treatment for five years exhibited decreased cardiac hypertrophy.

MDA Resource Center: We’re Here For You

Our trained specialists are here to provide one-on-one support for every part of your journey. Send a message below or call us at 1-833-ASK-MDA1 (1-833-275-6321). If you live outside the U.S., we may be able to connect you to muscular dystrophy groups in your area, but MDA programs are only available in the U.S.

Request Information