Vatiquinone (DB11917): A Comprehensive Monograph on a First-in-Class 15-Lipoxygenase Inhibitor for Neurodegenerative Disease

Executive Summary

Vatiquinone (DrugBank ID: DB11917) is an orally bioavailable, investigational small molecule therapeutic developed by PTC Therapeutics as a potential treatment for rare neurodegenerative and mitochondrial disorders. Chemically identified as a synthetic analog of vitamin E and a para-benzoquinone, Vatiquinone represents a first-in-class selective inhibitor of the enzyme 15-lipoxygenase (15-LO). Its primary mechanism of action is the modulation of critical pathways involved in oxidative stress, neuroinflammation, and a specific form of iron-dependent programmed cell death known as ferroptosis. By targeting 15-LO, Vatiquinone aims to mitigate the downstream pathological consequences of mitochondrial dysfunction, particularly the lipid peroxidation that drives neuronal cell death in diseases characterized by high levels of oxidative stress.

The principal clinical development program for Vatiquinone has focused on Friedreich's ataxia (FA), a rare, progressive, and life-shortening neuromuscular disorder for which there is a significant unmet medical need, especially in pediatric populations. The cornerstone of its regulatory submission was the pivotal Phase 3 MOVE-FA trial. The trial yielded a complex and challenging set of results: it failed to meet its prespecified primary endpoint of a statistically significant change in the overall modified Friedreich Ataxia Rating Scale (mFARS) score. However, the study did demonstrate a statistically significant and clinically meaningful benefit on the prespecified mFARS Upright Stability Subscale (USS), a key measure of disease progression in the younger, ambulatory FA patient population.

This signal of efficacy was substantially reinforced by data from long-term, open-label extension studies. When compared to matched natural history cohorts, Vatiquinone treatment was associated with a highly statistically significant and durable slowing of disease progression over several years, suggesting a profound disease-modifying effect. Furthermore, across its extensive clinical evaluation in over 500 patients, Vatiquinone has established a consistently favorable and well-tolerated safety profile, with no treatment-related serious adverse events reported in its key long-term studies.

Despite these positive long-term efficacy and safety signals, Vatiquinone's regulatory path has been arduous. PTC Therapeutics submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the treatment of FA in children and adults. The application was accepted and granted Priority Review. However, on its PDUFA date of August 19, 2025, the FDA issued a Complete Response Letter (CRL), denying approval. The agency concluded that the available data did not provide substantial evidence of efficacy and stipulated that an additional adequate and well-controlled clinical trial would be required to support a resubmission. This regulatory outcome places the future of Vatiquinone in a state of uncertainty, contingent upon the sponsor's decision to pursue a new confirmatory study in a competitive landscape that includes an approved therapy for adult FA patients.

Compound Profile and Medicinal Chemistry

A comprehensive understanding of Vatiquinone begins with its fundamental chemical identity, which dictates its pharmacological properties, formulation, and pharmacokinetic behavior. As a synthetic molecule derived from natural product chemistry, it possesses a unique structure that underpins its novel mechanism of action.

Identification and Nomenclature

Vatiquinone is identified across scientific literature and regulatory databases by a consistent set of names, codes, and registry numbers. This standardization is crucial for accurate tracking and cross-referencing of research and development activities.

• Generic Name: The officially recognized nonproprietary name for the compound is Vatiquinone.[1]
• Synonyms and Development Codes: Throughout its development history, the compound has been known by several names and codes. It was initially developed under the code EPI-743 (also stylized as EPI 743 or EPI743) by Edison Pharmaceuticals.[1] After its acquisition by PTC Therapeutics, it was also referred to as PTC-743 or PTC743.[1] Other common synonyms include alpha-Tocotrienol quinone, ATQ3, and Vincerenone.[1]
• Registry Numbers: The compound is cataloged in major chemical and pharmacological databases with unique identifiers:
• DrugBank Accession Number: DB11917 [1]
• CAS Number: 1213269-98-7 [1]
• UNII (Unique Ingredient Identifier): 6O85FK9I0X [1]
• ChEMBL ID: CHEMBL1812161 [1]

Chemical Structure and Properties

Vatiquinone is a complex organic molecule whose structure is a hybrid of a quinone ring and a long, unsaturated isoprenoid side chain.

• IUPAC Name: The systematic name for Vatiquinone is 2--3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione.[1]
• Molecular Formula: The empirical formula of the molecule is C29​H44​O3​.[1]
• Molecular Weight: The average molecular weight is approximately 440.67 g/mol, with a monoisotopic mass of approximately 440.3290 g/mol.[1]
• Structural Identifiers: The molecule's two-dimensional structure can be represented by standard chemical line notations:
• Canonical SMILES: CC1=C(C(=O)C(=C(C1=O)C)CC[C@@](C)(CC/C=C(\C)/CC/C=C(\C)/CCC=C(C)C)O)C [5]
• InChIKey: LNOVHERIIMJMDG-XZXLULOTSA-N [1]

Chemical Classification and Physicochemical Characteristics

The classification and physical properties of Vatiquinone are central to its identity as a drug candidate, influencing its biological activity, how it is formulated for administration, and its behavior within the body.

• Chemical Classification: Vatiquinone belongs to the class of organic compounds known as diterpenoids, which are formed from four isoprene units. More specifically, it is classified as a prenylquinone and a p-benzoquinone.[1] Its structure is described as a synthetic analog of both vitamin E (specifically, a chroman-ring-opened metabolite of alpha-tocotrienol) and coenzyme Q10, sharing features with both of these biologically important lipophilic molecules.[7]
• Physical Form and Appearance: At room temperature, Vatiquinone is an oily liquid, with a color ranging from colorless to light yellow.[4]
• Solubility and Lipophilicity: The compound is poorly soluble in aqueous solutions but is soluble in organic solvents such as ethanol and DMSO.[4] It is a highly lipophilic and hydrophobic molecule, a property quantified by its high calculated partition coefficient (cLogP) of 7.8.[1] This high lipophilicity is a defining characteristic that strongly influences its absorption and distribution.
• Storage and Stability: Vatiquinone is stable enough for shipping under ambient temperatures. For short-term storage (days to weeks), it should be kept dry, dark, and at 0-4 °C. For long-term stability (months to years), storage at -20 °C is recommended.[4]

The following table consolidates the key chemical and physical properties of Vatiquinone for ease of reference.

Table 1: Summary of Vatiquinone's Chemical and Physical Properties

Property	Value	Source(s)
Generic Name	Vatiquinone	1
DrugBank ID	DB11917	1
CAS Number	1213269-98-7	1
Development Codes	EPI-743, PTC-743	1
Synonyms	alpha-Tocotrienol quinone, ATQ3, Vincerenone	1
IUPAC Name	2--3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione	1
Molecular Formula	C29​H44​O3​	1
Average Molecular Weight	440.67 g/mol	1
Monoisotopic Mass	440.3290 g/mol	1
Chemical Class	Diterpenoid, Prenylquinone, p-Benzoquinone	1
Appearance	Oily liquid, colorless to light yellow	4
logP	7.81	1
Solubility	Soluble in ethanol and DMSO; poor aqueous solubility	4
Storage	-20 °C for long-term storage	4

Preclinical and Clinical Pharmacology

The pharmacological profile of Vatiquinone is defined by a highly specific mechanism of action that has become increasingly well-elucidated over the course of its development. This mechanism directly informs its pharmacodynamic effects and its pharmacokinetic behavior, providing a strong scientific rationale for its investigation in diseases driven by oxidative stress and mitochondrial dysfunction.

Mechanism of Action (MOA)

The understanding of Vatiquinone's mechanism of action has evolved significantly, shifting from a broad description as a general antioxidant to a precise definition centered on a single enzymatic target and its role in a specific cell death pathway. Initially, owing to its structural similarity to vitamin E, its mechanism was thought to be based on general antioxidant activity to reduce oxidative stress.[15] Further research described it as a modulator of oxidoreductases, such as NAD(P)H:quinone oxidoreductase 1, which acts to improve the overall cellular redox status.[10] However, subsequent and more definitive research has established a much more specific and compelling narrative.

Primary Target: Selective Inhibition of 15-Lipoxygenase (15-LO)

Vatiquinone is now characterized as a first-in-class, selective inhibitor of 15-lipoxygenase (15-LO), also known as arachidonate 15-lipoxygenase.[2] This enzyme is a pivotal regulator of interconnected pathways that control inflammation, oxidative stress, and cellular energy metabolism.[14] In pathological states, particularly those involving high levels of oxidative stress and free iron, 15-LO is activated and converts polyunsaturated fatty acids into lipid hydroperoxides, such as 15(S)-hydroperoxyeicosatetraenoic acid (15-HpETE).[14] The accumulation of these lipid hydroperoxides within cellular membranes compromises their integrity and triggers downstream signaling cascades that lead to cell death. By selectively inhibiting 15-LO, Vatiquinone is designed to block this critical initiating step, thereby preventing the accumulation of toxic lipid peroxides and promoting neuronal survival.[14]

Inhibition of Ferroptosis

The direct consequence of 15-LO inhibition by Vatiquinone is the suppression of ferroptosis, a distinct, iron-dependent form of regulated, non-apoptotic cell death driven by overwhelming lipid peroxidation.[9] This mechanism is particularly relevant to the pathophysiology of Friedreich's ataxia. FA is caused by a deficiency in the mitochondrial protein frataxin, which leads to mitochondrial iron accumulation and a state of chronic, heightened oxidative stress.[19] This combination of excess iron and oxidative stress creates an environment highly susceptible to ferroptotic cell death, which is believed to be a primary driver of neurodegeneration in the disease.[23] Vatiquinone's ability to inhibit ferroptosis thus represents a therapeutic strategy that directly targets a core pathogenic process in FA.[13]

This highly specific mechanism has been validated in preclinical studies. In vitro experiments using patient-derived fibroblasts demonstrated that Vatiquinone potently prevents cell death induced by specific triggers of ferroptosis, such as the glutathione peroxidase 4 (GPX4) inhibitor RSL3 or a combination of glutathione depletion (via L-buthionine-(S,R)-sulfoximine, or BSO) and excess iron.[4] The effective concentrations in these assays were in the nanomolar range (

EC50​ values of 24 nM and 30 nM in FA and Leigh syndrome fibroblasts, respectively), indicating high potency.[9] Critically, these studies also revealed the specificity of the mechanism; Vatiquinone had no protective effect against cell death induced by the general mitochondrial oxidative stress inducer paraquat or the mitochondrial complex I inhibitor rotenone.[27] This distinction is crucial, as it suggests Vatiquinone is not a broad-spectrum antioxidant but a targeted inhibitor of the 15-LO/ferroptosis axis. This mechanistic specificity provides a strong rationale for its efficacy in diseases where ferroptosis is a key contributor, while also explaining its lack of benefit in conditions where other forms of mitochondrial dysfunction or oxidative stress may be dominant, such as was observed in the MIT-E trial for mitochondrial seizures.[30]

Pharmacodynamics

The pharmacodynamic effects of Vatiquinone are the direct physiological and biochemical consequences of its mechanism of action. Administered orally, the molecule is capable of crossing the blood-brain barrier, allowing it to exert its effects within the central nervous system, the primary site of pathology in many of its target indications.[20]

The inhibition of 15-LO and subsequent reduction in oxidative stress leads to measurable changes in cellular biomarkers. Clinical studies have shown that Vatiquinone treatment leads to an augmentation of intracellular glutathione (GSH), the body's primary endogenous antioxidant, and a corresponding decrease in the ratio of oxidized glutathione (GSSG) to reduced glutathione (GSH).[4] This improvement in the GSSG/GSH "redox signature" serves as a key pharmacodynamic marker, providing

in vivo evidence of target engagement and biological activity that has been correlated with clinical improvement in disease symptoms.[13]

A thorough investigation of Vatiquinone's effect on cardiac electrophysiology was conducted to assess its safety profile. A concentration-QTc analysis in healthy volunteers found no statistically significant relationship between plasma Vatiquinone concentrations and the Fridericia-corrected QT interval (QTcF), even at supratherapeutic doses of 1400 mg, which are approximately 3.5 times the therapeutic dose.[22] The largest observed placebo-corrected mean change in QTcF was a clinically irrelevant 1.5 ms.[22] The study concluded that there is a minimal cardiac risk associated with Vatiquinone, as it does not have a clinically relevant effect on heart rate or cardiac conduction (PR and QRS intervals).[22]

Pharmacokinetics: Absorption, Distribution, Metabolism, and Excretion (ADME)

The pharmacokinetic profile of Vatiquinone is complex and is largely dictated by its high lipophilicity. This property profoundly influences its absorption and necessitates specific administration requirements, while its metabolism is primarily mediated by the cytochrome P450 system, creating potential for drug-drug interactions.

Absorption and Bioavailability

Vatiquinone exhibits a delayed and variable absorption pattern. Following oral administration, there is a characteristic lag time of 2 to 3 hours before plasma concentrations begin to rise.[14] The absorption process is prolonged, with a zero-order absorption duration lasting approximately 6 hours.[14] This is likely due to its high lipophilicity, which suggests a dual absorption pathway involving both direct entry into systemic circulation and association with chylomicrons for absorption via the lymphatic system.[14]

Most critically, the bioavailability of Vatiquinone is profoundly dependent on the presence of food. Population pharmacokinetic modeling revealed that administration with a medium-fat meal can increase drug exposure (AUC) by up to 25-fold when compared to administration under fasted conditions.[14] This massive food effect is a direct consequence of its poor aqueous solubility and high lipophilicity; dietary fats stimulate bile secretion, which emulsifies the drug into micelles, dramatically enhancing its solubilization and subsequent absorption from the gastrointestinal tract. This finding has critical implications for clinical practice, as inconsistent administration with respect to meals would lead to extreme variability in drug exposure and likely therapeutic failure. Consequently, all clinical trial protocols have mandated administration with food to ensure consistent and adequate bioavailability.[26]

Metabolism and Elimination

Hepatic elimination is the primary route of clearance for Vatiquinone.[13] The drug is extensively metabolized, primarily through the action of the cytochrome P450 isoform CYP3A4.[13] Major metabolic pathways include reduction of the quinone ring, oxidation on the side chain, and oxidative cleavage of the side chain via beta-oxidation, followed by Phase II conjugation reactions such as sulphation and glucuronidation.[13] Despite extensive metabolism, no single major metabolite (defined as >10% of drug-related substance) has been identified in circulation.[26] The estimated effective half-life is approximately 9 hours, supporting a three-times-daily dosing regimen to maintain therapeutic exposures.[26]

Drug-Drug Interactions (DDI)

Given the central role of CYP3A4 in its metabolism, Vatiquinone is susceptible to interactions with drugs that modulate this enzyme.

• Vatiquinone as a Victim: Clinical studies have confirmed that its exposure is significantly altered by potent CYP3A4 modulators. Co-administration with itraconazole, a strong CYP3A4 inhibitor, increased Vatiquinone's maximum concentration (Cmax​) and total exposure (AUC) by approximately 3.5-fold and 2.9-fold, respectively.[26] Conversely, co-administration with rifampin, a strong CYP3A4 inducer, decreased its Cmax​ and AUC by approximately 36% and 46%, respectively.[26] Physiologically based pharmacokinetic (PBPK) modeling predicts that moderate CYP3A4 inhibitors (e.g., fluconazole) and inducers (e.g., efavirenz) would have a weaker, though still notable, impact on Vatiquinone exposure.[35]
• Vatiquinone as a Perpetrator: The potential for Vatiquinone to affect the metabolism of other drugs is low. While in vitro studies suggested weak inhibition of CYP2C9 and CYP2C19, dedicated clinical DDI studies demonstrated that Vatiquinone has no clinically meaningful effect on the pharmacokinetics of substrates for CYP2C9 (tolbutamide), CYP2C19 (omeprazole), or the drug transporter BCRP (rosuvastatin).[13] PBPK modeling further predicted no significant risk of interaction with CYP3A4 or CYP1A2 substrates.[35]

Clinical Development and Efficacy

The clinical development of Vatiquinone has been extensive, spanning more than a decade and investigating its potential across a wide spectrum of rare neurological and mitochondrial diseases. The program has been characterized by a strategic pivot towards Friedreich's ataxia following mixed or negative results in other indications. The data generated, particularly from the FA program, present a complex picture of a drug with a strong biological rationale and compelling long-term signals, yet one that failed to meet the stringent requirements for regulatory approval in its pivotal trial.

The Friedreich's Ataxia (FA) Program

The most advanced and comprehensive clinical program for Vatiquinone has been for the treatment of Friedreich's ataxia, a debilitating neurodegenerative disease with no approved therapies for pediatric patients.

The Pivotal MOVE-FA Phase 3 Trial (NCT04577352)

The MOVE-FA study was the registration-directed trial designed to provide the definitive evidence of Vatiquinone's efficacy and safety in FA.[15]

• Trial Design: This was a global, randomized, parallel-arm, double-blind, placebo-controlled study with a 72-week treatment period, followed by a 24-week open-label extension.[39] The trial enrolled 146 patients aged 7 years and older with a genetically confirmed diagnosis of FA.[33] The primary efficacy analysis was prespecified for the modified intent-to-treat (mITT) population, which consisted of 123 patients between the ages of 7 and 21.[15]
• Primary Endpoint Outcome: The trial failed to meet its primary endpoint. There was no statistically significant difference in the change from baseline in the total modified Friedreich Ataxia Rating Scale (mFARS) score at 72 weeks between the Vatiquinone and placebo groups. The mean placebo-corrected change was -1.61 points, with a p-value of 0.14.[15]
• Key Secondary and Subscale Endpoint Outcomes: Despite the failure of the primary endpoint, the trial yielded statistically significant and clinically meaningful results on several prespecified secondary and subscale endpoints. The most critical finding was a significant treatment benefit on the mFARS Upright Stability Subscale (USS), which assesses functions related to balance, stance, and mobility. In the mITT population, patients treated with Vatiquinone showed a placebo-corrected improvement of -1.26 points on the USS, a result that was statistically significant (p=0.021).[15] Significant benefits were also observed in the bulbar subscale (p=0.044) and on the Modified Fatigue Impact Scale (MFIS) (p=0.025).[15]

The divergence between the primary and secondary endpoint results became the central issue in the drug's evaluation. The mFARS is a composite scale, and a treatment effect concentrated in one domain can be diluted when averaged into a total score. Natural history data from large patient registries have shown that for the younger, ambulatory FA population predominantly enrolled in MOVE-FA, disease progression is primarily driven by declines in functions measured by the USS.[18] In fact, within the MOVE-FA trial itself, the USS was the only mFARS subscale to show meaningful progression in the placebo group over the 72-week period, consistent with these natural history data.[33] This suggests that the USS was the most sensitive and clinically relevant measure of disease progression for this specific patient population. While the scientific argument for the importance of the USS result is strong, the failure to meet the designated primary endpoint created a significant regulatory hurdle.

Long-Term Extension (LTE) Studies

To assess the durability of the treatment effect, data from patients who rolled over into the open-label extension of the MOVE-FA trial, as well as from an earlier Phase 2 study, were analyzed and compared against matched external control cohorts from the Friedreich Ataxia Clinical Outcome Measures (FACOMS) natural history database.[47]

• Results: These long-term analyses produced highly compelling and statistically significant results. After 144 weeks (approximately 3 years) of treatment in the MOVE-FA extension study, participants receiving Vatiquinone demonstrated a 3.7-point benefit on the total mFARS score compared to the matched FACOMS cohort (p<0.0001; n=70).[18] This represents a clinically meaningful 50% slowing of overall disease progression over a three-year period.[18] Similarly, in an earlier study of adults with FA, 24 months of treatment resulted in a 4.8-point benefit on the mFARS relative to a matched natural history population (p<0.0001; n=41).[33] These data provided strong, durable evidence of a disease-modifying effect that was not fully captured within the 72-week timeframe of the placebo-controlled portion of the pivotal trial.

The Mitochondrial Disease Program

Prior to and concurrent with the FA program, Vatiquinone was investigated for other rare mitochondrial diseases, most notably for refractory epilepsy.

The MIT-E Trial for Refractory Epilepsy (NCT04378075)

This Phase 2/3 registration-directed trial was designed to evaluate Vatiquinone for the treatment of mitochondrial disease-associated seizures (MDAS) in pediatric patients.[30]

• Trial Design and Outcome: The MIT-E study was a double-blind, placebo-controlled trial that enrolled 68 children with genetically confirmed mitochondrial disease and refractory epilepsy.[30] The trial failed to achieve its primary endpoint, which was the reduction in the frequency of observable motor seizures during the 24-week placebo-controlled phase.[30]
• Subgroup Analysis: While the overall result was negative, the study did show some evidence of a treatment effect. In the largest subgroup of children with Leigh syndrome, a benefit was observed in key secondary endpoints, including a reduction in the occurrence of status epilepticus and disease-related hospitalizations.[30] However, these signals were not sufficient to support further development of Vatiquinone for the broad MDAS indication, and PTC Therapeutics subsequently discontinued its efforts in this area to focus on FA.[30]

Exploratory Indications

Vatiquinone's development history includes a broad range of early- to mid-stage clinical investigations into various other inherited mitochondrial and neurological disorders. Completed Phase 2 trials have been conducted for conditions such as Parkinson's Disease, Rett Syndrome, and Subacute Necrotizing Encephalomyelopathy (Leigh Syndrome).[1] Other trials for indications like Pearson Marrow-pancreas Syndrome and Autism Spectrum Disorder were terminated or withdrawn.[1] While these studies contributed to the overall understanding of the drug's safety profile, they did not yield efficacy signals strong enough to warrant advancement to Phase 3 development.

The following table provides a consolidated overview of the key clinical trials conducted for Vatiquinone.

Table 2: Comprehensive Summary of Key Vatiquinone Clinical Trials

Trial ID (Name)	Indication	Phase	Patients	Primary Endpoint	Key Outcome / Result	Source(s)
NCT04577352 (MOVE-FA)	Friedreich's Ataxia (FA)	3	146	Change in total mFARS score at 72 weeks	Failed primary endpoint (p=0.14). Met key secondary endpoint of change in mFARS Upright Stability Subscale (p=0.021).	15
NCT05515536 (MOVE-FA LTE)	Friedreich's Ataxia (FA)	3	140	Change in mFARS vs. Natural History	Met primary endpoint. Showed a 3.7-point benefit vs. FACOMS cohort at 144 weeks (p<0.0001), a 50% slowing of progression.	29
NCT04378075 (MIT-E)	Mitochondrial Disease Associated Seizures (MDAS)	2/3	68	Reduction in observable motor seizure frequency	Failed primary endpoint. Showed some evidence of effect in Leigh syndrome subgroup on secondary endpoints. Program discontinued for this indication.	29
NCT01728064	Friedreich's Ataxia (FA)	2	63	Change in vision	Did not meet primary vision endpoint. Showed trend towards neurological improvement on FARS. Long-term data showed a 4.8-point benefit vs. FACOMS at 24 months.	47
NCT01721733	Subacute Necrotizing Encephalomyelopathy (Leigh Syndrome)	2	N/A	Safety and Efficacy	Completed.	55
NCT01923584	Parkinson's Disease (PD)	2	15	Safety and Efficacy	Completed.	29

Safety and Tolerability Profile

Across a comprehensive clinical development program that has included over 500 patients with various rare diseases, Vatiquinone has consistently demonstrated a favorable and well-tolerated safety profile.[57] This robust safety database, with some patients having received treatment for up to 10 years, is a significant asset for the compound.[30]

Integrated Safety Analysis

In the pivotal MOVE-FA trial for Friedreich's ataxia, the overall safety profile was a key finding. The analysis showed no difference in the incidence of treatment-related adverse events between the Vatiquinone and placebo groups, indicating that the drug did not add significant toxicity over placebo.[44] This favorable profile was maintained in the long-term extension studies, where no treatment-related serious adverse events (SAEs) were reported.[18] Furthermore, no adverse events led to study discontinuation in key analyses, underscoring the drug's tolerability.[59]

Adverse Events

The most commonly reported adverse events associated with Vatiquinone treatment are generally mild to moderate in severity. An analysis of safety data presented for the MOVE-FA trial listed common adverse events as headache (35.6% in the treatment group), diarrhea (19.2%), nausea (17.8%), and abdominal pain (9.6%).[20] These events are typical for orally administered drugs and were not reported to be dose-limiting or to lead to significant morbidity.

Contraindications and Trial Exclusions

While no formal contraindications have been established for the investigational agent, the exclusion criteria used across its clinical trials provide insight into populations where caution is warranted. Consistently, studies have excluded patients with a known allergy to Vatiquinone or its formulation excipients, such as sesame oil.[39] Patients with significant pre-existing organ dysfunction, particularly hepatic impairment (defined as ALT or AST levels ≥2-3 times the upper limit of normal) or renal insufficiency, were also excluded.[39] Other common exclusions included clinically significant bleeding disorders or coagulopathy (INR ≥1.5 times ULN), pregnancy or lactation, and the use of potent CYP3A4 inhibitors or inducers due to the known pharmacokinetic interaction.[32]

Regulatory History and Future Outlook

The regulatory journey of Vatiquinone has been long and complex, marked by promising early designations, a strategic focus on Friedreich's ataxia, and a significant recent setback from the U.S. FDA. The drug's future is now contingent on navigating the path forward in light of this regulatory decision.

Development Timeline and Sponsorship

Vatiquinone, originally known as EPI-743, was first developed by Edison Pharmaceuticals, a company specializing in mitochondrial diseases that was later known as BioElectron Technology Corporation.[2] In 2019, the compound was acquired by PTC Therapeutics, which has since been responsible for its late-stage clinical development and regulatory submissions.[27]

Special Regulatory Designations

Reflecting the high unmet medical need in its target indications, Vatiquinone has accumulated numerous special designations from regulatory authorities in the United States and Europe.

• U.S. Food and Drug Administration (FDA): The FDA has granted Vatiquinone Orphan Drug Designation for several conditions, including Friedreich's ataxia (granted January 31, 2014), Rett syndrome, inherited mitochondrial diseases, and mitochondrial epilepsy.[3] For FA, it also received Fast Track Designation in March 2014, intended to expedite the review of drugs for serious conditions.[4] Additionally, it was granted Rare Pediatric Disease Designation for mitochondrial epilepsy.[67]
• European Medicines Agency (EMA): In Europe, Vatiquinone has received Orphan Designation for a range of diseases, including Friedreich ataxia (March 26, 2021), Leigh syndrome, MELAS, Alpers-Huttenlocher syndrome, and Pontocerebellar hypoplasia type 6.[66]

The U.S. FDA New Drug Application (NDA) for Friedreich's Ataxia

The culmination of years of clinical research was the submission of an NDA to the FDA for the treatment of FA.

• Submission and Review: On December 19, 2024, PTC Therapeutics announced the submission of the NDA for Vatiquinone for both children and adults with FA.[15] The submission was based on the totality of the evidence, including the placebo-controlled MOVE-FA trial and two long-term extension studies.[15] On February 19, 2025, the FDA accepted the NDA for filing and granted it Priority Review, a designation reserved for drugs that, if approved, would offer a significant improvement in the treatment of a serious condition. This set a Prescription Drug User Fee Act (PDUFA) target action date of August 19, 2025.[18]
• Complete Response Letter (CRL): On the PDUFA date, August 19, 2025, the FDA issued a Complete Response Letter (CRL), officially denying approval of Vatiquinone at that time.[17] The central reason cited in the CRL was that the application did not provide "substantial evidence of efficacy." The agency stated that an "additional adequate and well-controlled study would be needed" to support a future resubmission.[17] This decision indicates that while the FDA may have acknowledged the scientific rationale behind the USS endpoint and the compelling long-term data, these were ultimately deemed insufficient to overcome the failure of the single, pre-specified primary endpoint in the pivotal trial.

European Medicines Agency (EMA) Status

PTC Therapeutics has also been in communication with the EMA regarding a potential path to approval in Europe. The company has engaged in scientific advice procedures to determine if the MOVE-FA data could support a conditional marketing authorization application.[71] The EMA has also continued to engage on the drug's pediatric development, issuing a decision in May 2023 on a modification to an agreed-upon paediatric investigation plan (PIP).[72] The outcome of these discussions in light of the FDA's decision remains to be seen.

Future Outlook and Expert Analysis

The future of Vatiquinone is at a critical crossroads. PTC Therapeutics has publicly stated its disappointment with the FDA's decision and its intention to meet with the agency to discuss potential next steps to address the issues raised in the CRL.[21] In the interim, the company has committed to continuing all ongoing Vatiquinone studies, ensuring current participants maintain access to the drug.[73]

The most direct path to a potential approval in the United States would involve conducting a new, successful confirmatory Phase 3 trial. Based on the FDA's feedback and the scientific evidence from MOVE-FA, such a trial would almost certainly need to designate the mFARS USS, or a similarly validated measure of ambulatory function, as its primary endpoint. This would align the trial's primary objective with the clinical domain where Vatiquinone has shown its clearest effect and which is most relevant to the target patient population.

However, conducting another large, long-term global trial for a rare disease is a substantial undertaking, requiring significant time and financial investment. The company's decision will involve a careful strategic calculation, weighing the cost and risk of a new trial against the drug's strong safety profile, the compelling long-term efficacy data, and the persistent high unmet medical need for a safe and effective treatment for children with FA.

Competitive Landscape and Strategic Analysis

Vatiquinone's development and regulatory journey cannot be fully understood without considering its position within the therapeutic landscape for Friedreich's ataxia, which is dominated by a single approved competitor and a pipeline of emerging therapies.

The Approved Competitor: Omaveloxolone (Skyclarys™)

The only therapy currently approved by the FDA specifically for the treatment of Friedreich's ataxia is Omaveloxolone (brand name Skyclarys™), developed by Reata Pharmaceuticals and now marketed by Biogen.[45] It is approved for use in patients aged 16 years and older.[33]

• Contrasting Mechanism of Action: Omaveloxolone operates via a distinct, though conceptually related, mechanism of action. It is an activator of the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2).[18] In FA, the Nrf2 pathway is impaired. By activating Nrf2, Omaveloxolone upregulates a broad array of endogenous antioxidant and anti-inflammatory genes, thereby restoring redox balance and mitigating oxidative stress.[33] While Vatiquinone directly inhibits a specific pro-inflammatory enzyme (15-LO), Omaveloxolone works more broadly by boosting the cell's own defense systems.
• Pivotal Clinical Trial Performance: A key differentiator between the two drugs is their performance in their respective pivotal trials. In its registrational MOXIe trial, Omaveloxolone successfully met its primary endpoint, demonstrating a statistically significant improvement in the total mFARS score compared to placebo over 48 weeks.[75] This clear-cut positive result on the primary endpoint provided a straightforward basis for its regulatory approval.

Strategic Positioning and Future Implications

Vatiquinone's development strategy was heavily focused on a key area of unmet need not addressed by Skyclarys: the pediatric population.

• The Pediatric Niche: Skyclarys is only approved for patients aged 16 and older. Vatiquinone's pivotal MOVE-FA trial predominantly enrolled children and adolescents, and its strongest efficacy signal was in this population.[15] PTC's stated goal was for Vatiquinone to become the first and only approved therapy for children with FA.[18] The FDA's CRL has severely jeopardized this primary strategic advantage.
• Closing Competitive Window: The regulatory delay for Vatiquinone creates a critical window of opportunity for its competitor. Biogen is already conducting clinical trials of Omaveloxolone in pediatric FA patients aged 2 to 15 (e.g., the BOLD study and NCT06953583) with the explicit goal of securing a label expansion.[84] If Biogen is successful in obtaining a pediatric indication before Vatiquinone can complete a new trial and resubmit its NDA, Vatiquinone will lose its most significant potential differentiator and face the challenge of entering a market where a competitor is already established across all age groups.

The regulatory setback for Vatiquinone is therefore of high strategic consequence. The company had built a compelling narrative for approval based on the totality of its data, including the scientifically sound rationale for the USS endpoint's relevance, the impressive long-term efficacy data against natural history, the robust safety profile, and the significant unmet need. The FDA's decision to grant Priority Review initially suggested that this narrative was being considered seriously.[18] However, the final CRL underscores a strict adherence to regulatory precedent, where the failure of a single, pre-specified primary endpoint in a pivotal trial is exceedingly difficult to overcome, regardless of the strength of supportive secondary or exploratory data. This outcome places Vatiquinone in a precarious position, facing a longer, more costly, and riskier path to market while its main competitor seeks to solidify its market position. The case of Vatiquinone will likely serve as an important lesson for drug developers in the rare disease space regarding the paramount importance of aligning primary endpoint selection with both the specific disease pathophysiology and the rigorous expectations of regulatory authorities.

Conclusion

Vatiquinone is a pioneering investigational therapeutic with a highly specific and scientifically compelling mechanism of action as a first-in-class selective inhibitor of 15-lipoxygenase. Its development has been anchored by a strong rationale to combat neurodegeneration in Friedreich's ataxia and other mitochondrial diseases by targeting the critical pathway of ferroptosis. The compound has an extensively documented and favorable safety profile, a significant asset for any drug candidate, particularly one intended for chronic use in pediatric and adult populations.

Despite these strengths, the clinical efficacy data have been complex. While the pivotal MOVE-FA trial failed to meet its primary endpoint on the overall mFARS scale, it provided a clear and statistically significant signal of benefit in the mFARS Upright Stability Subscale—the most relevant clinical domain for the young, ambulatory population studied. This signal was powerfully reinforced by long-term extension data showing a durable and clinically meaningful 50% slowing of disease progression compared to natural history.

Ultimately, this complex data package was insufficient to meet the high bar for regulatory approval in the United States. The FDA's Complete Response Letter, citing a lack of substantial evidence of efficacy and requiring an additional confirmatory trial, has placed the program at a critical juncture. The future of Vatiquinone now depends on the sponsor's ability and willingness to undertake this significant new clinical investment. The path forward is challenging, not only due to the inherent risks of clinical development but also due to the closing competitive window as the currently approved therapy for adults, Omaveloxolone, is now being studied in the pediatric population that was Vatiquinone's key strategic target. While the scientific promise of Vatiquinone remains, its journey to becoming a potential therapy for patients with Friedreich's ataxia has become significantly more uncertain.

Works cited

1. Vatiquinone: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed September 27, 2025, https://go.drugbank.com/drugs/DB11917
2. Vatiquinone - Drug Targets, Indications, Patents - Patsnap Synapse, accessed September 27, 2025, https://synapse.patsnap.com/drug/7e5d44ca4976435bb93403859189a7a8
3. Search Orphan Drug Designations and Approvals - FDA, accessed September 27, 2025, https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=418413
4. Vatiquinone | EPI-743 | CAS#1213269-98-7 | Anti-Oxidant - MedKoo Biosciences, accessed September 27, 2025, https://www.medkoo.com/products/7862
5. Vatiquinone | C29H44O3 | CID 46184405 - PubChem, accessed September 27, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/Vatiquinone
6. Vatiquinone for Friedreich's ataxia, accessed September 27, 2025, https://friedreichsataxianews.com/friedreichs-ataxia-experimental-treatments/epi-743-vatiquinone/
7. EPI-743 (α-Tocotrienol quinone) | Vitamin E Analog - MedchemExpress.com, accessed September 27, 2025, https://www.medchemexpress.com/epi-743.html
8. VATIQUINONE - precisionFDA, accessed September 27, 2025, https://precision.fda.gov/ginas/app/ui/substances/30289d97-ff25-4050-bf6f-ccc03727d3de
9. Vatiquinone (CAS 1213269-98-7) - Cayman Chemical, accessed September 27, 2025, https://www.caymanchem.com/product/26819/vatiquinone
10. Vatiquinone, 1213269-98-7, 95 (HPLC) Sigma-Aldrich, accessed September 27, 2025, https://www.sigmaaldrich.com/US/en/product/sigma/sml3614
11. EPI 743 | 1213269-98-7 - ChemicalBook, accessed September 27, 2025, https://www.chemicalbook.com/ChemicalProductProperty_EN_CB32717758.htm
12. Vatiquinone | C29H44O3 - ChemSpider, accessed September 27, 2025, https://www.chemspider.com/Chemical-Structure.26632368.html
13. Full article: Absorption, distribution, metabolism and excretion of 14C-vatiquinone in rats, dogs, and human subjects - Taylor & Francis Online, accessed September 27, 2025, https://www.tandfonline.com/doi/full/10.1080/00498254.2023.2245459
14. Characterizing Population Pharmacokinetics of Vatiquinone in ..., accessed September 27, 2025, https://www.mdpi.com/1424-8247/18/9/1339
15. Vatiquinone (PTC-743) - Friedreich's Ataxia Research Alliance, accessed September 27, 2025, https://www.curefa.org/drug-development/vatiquinone-ptc-743/
16. www.curefa.org, accessed September 27, 2025, https://www.curefa.org/drug-development/vatiquinone-ptc-743/#:~:text=The%20mechanism%20of%20action%20was,activity%20to%20reduce%20oxidative%20stress.
17. FDA Rejects Vatiquinone as Potential Friedreich Ataxia Treatment - - PracticalNeurology, accessed September 27, 2025, https://practicalneurology.com/news/fda-rejects-vatiquinone-as-potential-friedreich-ataxia-treatment/2483217/
18. FDA Accepts NDA for Vatiquinone as Potential Treatment for Friedreich Ataxia, accessed September 27, 2025, https://www.neurologylive.com/view/fda-accepts-nda-for-vatiquinone-potential-treatment-friedreich-ataxia
19. Vatiquinone: What is it and is it FDA approved? - Drugs.com, accessed September 27, 2025, https://www.drugs.com/history/vatiquinone.html
20. Safety and Efficacy of Vatiquinone Treatment in Friedreich Ataxia Patients from MOVE-FA, accessed September 27, 2025, https://www.euroataxia.org/wp-content/uploads/2024/12/ICAR_ATAXIAUK_MOVE-FA_NOV20242.pdf
21. PTC Therapeutics Receives Complete Response Letter for Vatiquinone NDA, accessed September 27, 2025, https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-receives-complete-response-letter-vatiquinone
22. Characterizing Population Pharmacokinetics of Vatiquinone in Healthy Volunteers and Patients with Friedreich's Ataxia - ResearchGate, accessed September 27, 2025, https://www.researchgate.net/publication/395379369_Characterizing_Population_Pharmacokinetics_of_Vatiquinone_in_Healthy_Volunteers_and_Patients_with_Friedreich's_Ataxia
23. PTC Therapeutics Receives Complete Response Letter for Vatiquinone NDA - PR Newswire, accessed September 27, 2025, https://www.prnewswire.com/news-releases/ptc-therapeutics-receives-complete-response-letter-for-vatiquinone-nda-302533332.html
24. PTC Therapeutics Announces Positive Results from Long-Term Treatment Studies and Updates on Regulatory Progress for Vatiquinone Friedreich Ataxia Program, accessed September 27, 2025, https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-positive-results-long-term-treatment
25. PTC Therapeutics Announces Positive Results from Long-Term Treatment Studies and Updates on Regulatory Progress for Vatiquinone Friedreich Ataxia Program - PR Newswire, accessed September 27, 2025, https://www.prnewswire.com/news-releases/ptc-therapeutics-announces-positive-results-from-long-term-treatment-studies-and-updates-on-regulatory-progress-for-vatiquinone-friedreich-ataxia-program-302269891.html
26. Effect of Itraconazole, a CYP3A4 Inhibitor, and Rifampin, a CYP3A4 ..., accessed September 27, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11609057/
27. Evaluating the efficacy of vatiquinone in preclinical models of mitochondrial disease - PMC, accessed September 27, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11177993/
28. Evaluating the efficacy of vatiquinone in preclinical models of Leigh syndrome and GPX4 deficiency - PubMed, accessed September 27, 2025, https://pubmed.ncbi.nlm.nih.gov/39930437/
29. Evaluating the efficacy of vatiquinone in preclinical models of Leigh syndrome and GPX4 deficiency - PMC, accessed September 27, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11812209/
30. PTC Therapeutics Announces Results from MIT-E Clinical Trial of Vatiquinone for the Treatment of Mitochondrial Disease Associated Seizures, accessed September 27, 2025, https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-results-mit-e-clinical-trial
31. Vatiquinone not likely to raise cardiac risk with FA, study finds, accessed September 27, 2025, https://friedreichsataxianews.com/news/vatiquinone-not-likely-raise-cardiac-risk-fa-study/
32. NCT05485987 | A Study of Vatiquinone for the Treatment of Participants With Friedreich Ataxia | ClinicalTrials.gov, accessed September 27, 2025, https://www.clinicaltrials.gov/study/NCT05485987
33. FDA Denies Approval for Friedreich Ataxia Agent Vatiquinone, Citing More Efficacy Needed, accessed September 27, 2025, https://www.neurologylive.com/view/fda-denies-approval-friedreich-ataxia-agent-vatiquinone-citing-more-efficacy-needed
34. Vatiquinone Pharmacokinetics Influenced by CYP3A4 Inhibitors and Inducers in Phase 1 Study | NeurologyLive, accessed September 27, 2025, https://www.neurologylive.com/view/vatiquinone-pharmacokinetics-influenced-cyp3a4-inhibitors-inducers-phase-1-study
35. Determination of Vatiquinone Drug-Drug Interactions, as CYP450 Perpetrator and Victim, Using Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation - PubMed, accessed September 27, 2025, https://pubmed.ncbi.nlm.nih.gov/39308341/
36. Clinical Drug-Drug Interaction Between Vatiquinone, a 15-Lipoxygenase Inhibitor, and Rosuvastatin, a Breast Cancer Resistance Protein Substrate - PubMed, accessed September 27, 2025, https://pubmed.ncbi.nlm.nih.gov/36478438/
37. Evaluation of vatiquinone drug-drug interaction potential in vitro and in a phase 1 clinical study with tolbutamide, a CYP2C9 substrate, and omeprazole, a CYP2C19 substrate, in healthy subjects - PubMed, accessed September 27, 2025, https://pubmed.ncbi.nlm.nih.gov/36166059/
38. PTC Therapeutics Announces Topline Results from Vatiquinone MOVE-FA Registration-Directed Trial, accessed September 27, 2025, https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-topline-results-vatiquinone-move-fa
39. NCT04577352 | A Study to Assess the Efficacy and Safety of Vatiquinone for the Treatment of Participants With Friedreich Ataxia | ClinicalTrials.gov, accessed September 27, 2025, https://www.clinicaltrials.gov/study/NCT04577352
40. A Randomized, Parallel-Arm, Double-Blind, Placebo-Controlled Study with Open-Label Extension to Assess the Efficacy and Safety of Vatiquinone for the Treatment of Friedreich ataxia (MOVE-FA) - Orphanet, accessed September 27, 2025, https://www.orpha.net/en/research-trials/clinical-trial/611438?name=&mode=&country=&recruiting=0&terminated=0
41. A Randomized, Parallel-Arm, Double-Blind, Placebo-Controlled Study With Open-Label Extension to Assess the Efficacy and Safety of Vatiquinone for the Treatment of Friedreich Ataxia (MOVE-FA), accessed September 27, 2025, https://www.curefa.org/clinical-studies/a-randomized-parallel-arm-double-blind-placebo-controlled-study-with-open-label-extension-to-assess-the-efficacy-and-safety-of-vatiquinone-for-the-treatment-of-friedreich-ataxia-move-fa/
42. PTC Therapeutics Announces Vatiquinone NDA Submission to FDA for the Treatment of Children and Adults Living with Friedreich Ataxia, accessed September 27, 2025, https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-vatiquinone-nda-submission-fda
43. Improvement in Upright Stability subscale of mFARS with Vatiquinone Treatment in MOVE-FA: a Phase 3, Double-blind, Placebo-controlled Trial - MDA Clinical & Scientific Conference 2026, accessed September 27, 2025, https://www.mdaconference.org/abstract-library/improvement-in-upright-stability-subscale-of-mfars-with-vatiquinone-treatment-in-move-fa-a-phase-3-double-blind-placebo-controlled-trial/
44. Safety and Efficacy of Vatiquinone Treatment in Friedreich Ataxia Patients from MOVE-FA: a Phase 3, Double-blind, Placebo-controlled Trial - MDS Abstracts, accessed September 27, 2025, https://www.mdsabstracts.org/abstract/safety-and-efficacy-of-vatiquinone-treatment-in-friedreich-ataxia-patients-from-move-fa-a-phase-3-double-blind-placebo-controlled-trial/
45. FDA Rejects PTC Therapeutics' Friedreich's Ataxia Drug - BioSpace, accessed September 27, 2025, https://www.biospace.com/fda/fda-rejects-ptc-therapeutics-friedreichs-ataxia-drug
46. FDA accepts new drug application for vatiquinone to treat Friedreich's ataxia, accessed September 27, 2025, https://www.contemporarypediatrics.com/view/fda-accepts-new-drug-application-for-vatiquinone-to-treat-friedreich-s-ataxia
47. Long-term vatiquinone treatment slows FA disease progression relative to FACOMS Natural History - MDA Clinical & Scientific Conference 2026, accessed September 27, 2025, https://www.mdaconference.org/abstract-library/long-term-vatiquinone-treatment-slows-fa-disease-progression-relative-to-facoms-natural-history/
48. PTC Therapeutics Announces Positive Results from Long-Term Treatment Studies and Updates on Regulatory Progress for Vatiquinone Friedreich Ataxia Program, accessed September 27, 2025, https://www.curefa.org/news/ptc-therapeutics-announces-positive-results-from-long-term-treatment-studies-and-updates-on-regulatory-progress-for-vatiquinone-friedreich-ataxia-program/
49. PTC Therapeutics Announces Initiation of a Registration-Directed Clinical Trial to Evaluate Vatiquinone in Mitochondrial Epilepsy, accessed September 27, 2025, https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-initiation-registration-directed
50. Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy (MIT-E) — New England Consortium of Metabolic Programs, accessed September 27, 2025, https://www.newenglandconsortium.org/vatiquinone-for-treating-mitochondrial-disease-in-participants-with-refractory-epilepsy-mite
51. PTC Therapeutics Announces Results from MIT-E Clinical Trial of Vatiquinone for the Treatment of Mitochondrial Disease Associated Seizures - PR Newswire, accessed September 27, 2025, https://www.prnewswire.com/news-releases/ptc-therapeutics-announces-results-from-mit-e-clinical-trial-of-vatiquinone-for-the-treatment-of-mitochondrial-disease-associated-seizures-301867528.html
52. PTC's Vatiquinone Fails Second Trial in as Many Months - BioSpace, accessed September 27, 2025, https://www.biospace.com/ptc-s-vatiquinone-fails-second-trial-in-as-many-months
53. FDA rejection derails PTC Therapeutics' rare disease hopeful - Fierce Biotech, accessed September 27, 2025, https://www.fiercebiotech.com/biotech/ptc-therapeutics-friedreichs-ataxia-hopes-derailed-crl-fda
54. Vatiquinone Completed Phase 2 Trials for Parkinson's Disease (PD) Treatment - DrugBank, accessed September 27, 2025, https://go.drugbank.com/drugs/DB11917/clinical_trials?conditions=DBCOND0053495&phase=2&purpose=treatment&status=completed
55. Vatiquinone Completed Phase 2 Trials for Subacute Necrotizing Encephalomyelopathy Treatment | DrugBank Online, accessed September 27, 2025, https://go.drugbank.com/drugs/DB11917/clinical_trials?conditions=DBCOND0115209&phase=2&purpose=treatment&status=completed
56. Vatiquinone Completed Phase 2 Trials for Friedreich's Ataxia Treatment | DrugBank Online, accessed September 27, 2025, https://go.drugbank.com/drugs/DB11917/clinical_trials?conditions=DBCOND0037758&phase=2&purpose=treatment&status=completed
57. Vatiquinone Phase 3 Trial Initiated for Potential Treatment of Friedreich Ataxia, accessed September 27, 2025, https://practicalneurology.com/news/vatiquinone-phase-3-trial-initiated-for-potential-treatment-of-friedreich-ataxia/2469445/
58. PTC Therapeutics Announces Initiation of Global Phase 3 Clinical Trial to Evaluate Vatiquinone in Friedreich Ataxia, accessed September 27, 2025, https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-announces-initiation-global-phase-3-clinical
59. FDA issues CRL for vatiquinone to treat Friedreich ataxia - Contemporary Pediatrics, accessed September 27, 2025, https://www.contemporarypediatrics.com/view/fda-issues-crl-for-vatiquinone-to-treat-friedreich-s-ataxia
60. Safety and Efficacy of Vatiquinone Treatment in Friedreich Ataxia Patients from MOVE-FA: a Phase 3, Double-blind, Placebo-controlled Trial - MDA Conference, accessed September 27, 2025, https://www.mdaconference.org/abstract-library/safety-and-efficacy-of-vatiquinone-treatment-in-friedreich-ataxia-patients-from-move-fa-a-phase-3-double-blind-placebo-controlled-trial/
61. FDA Issues CRL for Vatiquinone in Friedreich Ataxia, Requests More Efficacy Data | AJMC, accessed September 27, 2025, https://www.ajmc.com/view/fda-issues-crl-for-vatiquinone-in-friedreich-ataxia-requests-more-efficacy-data
62. Study Details | NCT01370447 | EPI-743 for Mitochondrial Respiratory Chain Diseases, accessed September 27, 2025, https://www.clinicaltrials.gov/study/NCT01370447
63. A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy - ClinicalTrials.Veeva, accessed September 27, 2025, https://ctv.veeva.com/study/a-study-to-evaluate-efficacy-and-safety-of-vatiquinone-for-treating-mitochondrial-disease-in-partici
64. A Study of Vatiquinone for the Treatment of Participants With Friedreich Ataxia, Trial ID PTC743-NEU-005-FA | PTC Therapeutics, accessed September 27, 2025, https://clinicaltrials.ptcbio.com/trials/PTC743-NEU-005-FA
65. Vatiquinone -PTC Therapeutics - AdisInsight - Springer, accessed September 27, 2025, https://adisinsight.springer.com/drugs/800033222
66. Vatiquinone - Orphanet, accessed September 27, 2025, https://www.orpha.net/en/drug/substance/285822?name=
67. Vatiquinone Proceeds to Phase 2/3 Studies for Treatment of Mitochondrial Epilepsy, accessed September 27, 2025, https://practicalneurology.com/news/vatiquinone-proceeds-to-phase-23-studies-for-treatment-of-mitochondrial-epilepsy/2469409/
68. www.curefa.org, accessed September 27, 2025, https://www.curefa.org/drug-development/vatiquinone-ptc-743/#:~:text=Vatiquinone%20has%20been%20granted%20Orphan,and%20Drug%20Administration%20(FDA).
69. PTC Therapeutics announces positive updates from their phase III trial of Vatiquinone in FA, accessed September 27, 2025, https://www.ataxia.org.uk/research-news/ptc-therapeutics-announces-positive-updates-from-their-phase-iii-trial-of-vatiquinone-in-fa/
70. PTC Therapeutics announces that the FDA has not approved Vatiquinone to treat FA in adults and children - Ataxia UK, accessed September 27, 2025, https://www.ataxia.org.uk/research-news/ptc-therapeutics-announces-that-the-fda-has-not-approved-vatiquinone-to-treat-fa-in-adults-and-children/
71. Update from PTC Therapeutics on their MOVE-FA programme for Friedreich's ataxia, accessed September 27, 2025, https://www.ataxia.org.uk/research-news/results-from-the-ptc-therapeutics-move-fa-trial-for-friendreichs-ataxia/
72. EMEA-001238-PIP03-21-M01 - paediatric investigation plan | European Medicines Agency (EMA), accessed September 27, 2025, https://www.ema.europa.eu/en/medicines/human/paediatric-investigation-plans/emea-001238-pip03-21-m01
73. Pharma News - National Ataxia Foundation, accessed September 27, 2025, https://www.ataxia.org/pharmanews/
74. PTC's vatiquinone approval hopes dashed in Friedreich's Ataxia, accessed September 27, 2025, https://www.pharmaceutical-technology.com/news/ptc-vatiquinone-fda-rejection-friedreich-ataxia/
75. Topic 2.3. Therapies approved or under investigation - Clinical Management Guidelines for Friedreich Ataxia, accessed September 27, 2025, https://frdaguidelines.org/2-3/
76. Omaveloxolone: Uses, Interactions, Mechanism of Action - DrugBank, accessed September 27, 2025, https://go.drugbank.com/drugs/DB12513
77. go.drugbank.com, accessed September 27, 2025, https://go.drugbank.com/drugs/DB12513#:~:text=Omaveloxolone%20acts%20as%20an%20activator,and%20Nrf2%20activity%20is%20lower.
78. Omaveloxolone: Uses, Dosage, Side Effects & Warnings - Drugs.com, accessed September 27, 2025, https://www.drugs.com/omaveloxolone.html
79. Omaveloxolone - Wikipedia, accessed September 27, 2025, https://en.wikipedia.org/wiki/Omaveloxolone
80. What is the mechanism of Omaveloxolone? - Patsnap Synapse, accessed September 27, 2025, https://synapse.patsnap.com/article/what-is-the-mechanism-of-omaveloxolone
81. Freidreich's Ataxia Treatment Update, accessed September 27, 2025, https://www.mda.org/sites/default/files/2023/03/MedEd-March-2023-friedreichs-ataxia-treatment-update.pdf
82. Clinical Trial Results - SKYCLARYS® (omaveloxolone), accessed September 27, 2025, https://www.skyclarys.com/en-us/home/why-skyclarys/efficacy.html
83. Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study) - PubMed, accessed September 27, 2025, https://pubmed.ncbi.nlm.nih.gov/33068037/
84. Pipeline - Biogen, accessed September 27, 2025, https://www.biogen.com/science-and-innovation/pipeline.html
85. NCT06953583 - Clinical Trials - Study Details, accessed September 27, 2025, https://www.biogentriallink.com/en-us/home/find-a-clinical-trial/clinical-trials-study-details.html?nctId=NCT06953583
86. NCT06054893 | A Study to Find Out How BIIB141 (Omaveloxolone) is Processed in the Body and to Learn More About Its Safety in Participants With Friedreich's Ataxia Aged 2 to 15 Years Old | ClinicalTrials.gov, accessed September 27, 2025, https://www.clinicaltrials.gov/study/NCT06054893
87. Omaveloxolone Dose Finding Study in Children With Friedreich's Ataxia (BOLD), accessed September 27, 2025, https://www.curefa.org/clinical-studies/omaveloxolone-dose-finding-study-in-children-with-friedreichs-ataxia/