Idebenone Accepted by FDA for Priority Review for Leber Hereditary Optic Neuropathy (LHON)

FDA grants Priority Review to idebenone for Leber Hereditary Optic Neuropathy (LHON), a disease for which there are no existing approved treatments in the U.S.; action date of February 28, 2026

• People living with LHON suffer from rapid and severe loss of central vision due to mitochondrial dysfunction of retinal ganglion cells.¹
• Idebenone has the potential to be the first and only clinically proven short-chain benzoquinone, designed to target the underlying cause of LHON, mitochondrial dysfunction, thereby preserving, protecting and reactivating retinal ganglion cell function.^2,3,4,5,6
• The submission was based on the safety and efficacy data from Phase 3 (RHODOS) and Phase 4 (LEROS) studies.
  

PARMA, Italy and BOSTON, Sept. 22, 2025 (GLOBE NEWSWIRE) --  Chiesi Global Rare Diseases, a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people living with rare diseases, today announced the US Food and Drug Administration (FDA) is evaluating the regulatory submission of idebenone to treat Leber Hereditary Optic Neuropathy (LHON). The target action date for the FDA decision is February 28, 2026. If approved, idebenone will be the first and only clinically proven therapy for LHON in the United States. The drug is already approved, under the name Raxone^®, across EU countries (EMA, 2015) and ex-EU including UK (2015), Israel (2017), South Korea (2019), Serbia (2019), Switzerland (2014), Chile (2024), Bahrain (2025) and Taiwan (2025).

“LHON changes lives in an instant. This review brings hope of the first-ever approved treatment in the U.S. for LHON, one of the most prevalent mitochondrial diseases,” said Malinda Marsh, Chris Marsh, and Lissa Poincenot, Parents of children affected by LHON and Co-Founders of LHON Collective.

“For years we have been proud to provide idebenone to individuals outside the U.S. living with LHON. Now we are eager for the opportunity to introduce this clinically proven therapeutic option to the U.S., giving hope where there has been none,” said Mitch Goldman, Senior Vice President, R&D, Chiesi Global Rare Diseases. “Idebenone is designed to target mitochondrial dysfunction of retinal ganglion cells, the underlying cause of LHON. Data from our clinical studies and in-market experience suggest that idebenone has a favorable safety profile and the potential to improve vision. Our collaboration with FDA’s Division of Ophthalmology reflects a shared commitment to rare disease innovation. Their guidance on this path has been invaluable, and we’re hopeful that idebenone will become the first FDA-approved treatment for LHON.”

"LHON is a serious condition marked by rapid central vision loss, often beginning in one eye and quickly affecting the other, placing a profound and immediate burden on patients and their loved ones. If approved in the United States, idebenone would represent a meaningful advancement in treatment, offering hope to the LHON community,” said Nancy J Newman, MD, LeoDelle Jolley Chair in Ophthalmology at Emory University School of Medicine.

About Leber Hereditary Optic Neuropathy (LHON)

LHON is an inherited mitochondrial disorder that leads to progressive, rapid and severe vision loss. It is caused by genetic mutations that impair the ability of retinal ganglion cells — the nerve cells in the eye responsible for transmitting visual information — to produce the energy they need to function properly and remain healthy. Retinal ganglion cells located in the macular region of the retina (the area responsible for sharp, detailed central vision and color perception) are especially sensitive to this dysfunction, which explains why LHON initially and primarily affects central vision. Central vision is critical for detailed tasks such as reading, driving, and recognizing faces.

LHON often begins as a sudden, painless clouding or blurring accompanied by loss of sharpness and color vision.⁷ In 75% of cases, the onset of vision loss occurs in one eye first, followed by the other eye within a few weeks or months.¹ Beyond vision impairment, the condition often has a profound and lifelong impact on independence, education, employment and quality of life.

LHON can affect about 1 in 15,000 to 50,000 people worldwide and predominantly affects young men between the ages of 15 and 35, with men being 3-5 times more likely to develop the disease.⁸

About Idebenone clinical studies

Idebenone’s New Drug Application was accepted for review. This includes data from randomized placebo-controlled trial, as well as open-label interventional and observational studies that confirmed benefits in broader patient populations. Efficacy has been observed in the three most common mitochondrial DNA mutations (m.11778G>A, m.3460G>A, m.14484T>C) and rarer variants, reinforcing the broad therapeutic potential of idebenone in both adult and adolescent LHON patients.

In the Phase 3 study (RHODOS), a total of 85 patients with LHON, aged 14 to 65 years, carrying one of the three primary mitochondrial DNA mutations (m.11778G>A, m.3460G>A, or m.14484T>C), and with disease duration of ≤5 years, were enrolled in a 24-week, randomized, double-blind, placebo-controlled Phase 3 trial. ​

The primary efficacy endpoint was the best recovery of visual acuity (VA), defined as the change from baseline to week 24 in the eye showing the most improvement or least deterioration, measured using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Results (mITT): idebenone group (n=53): logMAR –0.136 (~+6 ETDRS letters) Placebo group (n=28): logMAR –0.036 (~+1 ETDRS letter) p = 0.0862.​

Statistically significant improvements were observed in: Change in best visual acuity (VA): idebenone: logMAR –0.037 (+1 letter) Placebo: logMAR +0.123 (–6 letters) p = 0.0152; Change in VA in the best eye: idebenone: logMAR –0.030 (+1 letter) Placebo: logMAR +0.098 (–6 letters) p = 0.0126. Post-Hoc Responder Analysis: A higher proportion of patients in the idebenone group achieved clinically meaningful improvements in visual acuity compared to placebo. These findings were consistent across multiple definitions of response and were further supported by propensity score–weighted analyses.​

In the Phase 4 study (LEROS), the primary endpoint was the proportion of eyes achieving a Clinically Relevant Benefit (CRB) at Month 12. CRB was defined as either a Clinically Relevant Recovery (CRR) or Clinically Relevant Stabilization (CRS) of visual acuity (VA) from baseline. The analysis focused on patients who initiated treatment with idebenone within ≤1 year of symptom onset, compared to a matched external natural history (NH) control group. At 12 months, 42.3% of eyes in the idebenone group achieved CRB versus 20.7% in the NH control group (OR 2.29; p = 0.002). At 24 months, the benefit was sustained: 52.9% of eyes in the idebenone group vs 36.0% in the NH group (OR 2.08; p = 0.0297). A secondary analysis in patients who started treatment >1 year after symptom onset also showed a statistically significant benefit: At 12 months: 50.3% (idebenone) vs 38.6% (NH) (OR 1.93; p = 0.0087). In a post-hoc responder analysis, the odds of achieving an Overall Benefit (OB), defined as either achieving CRR or no-CRW (no-Clinical Relevant Worsening:  Visual acuity remains stable without deterioration > 0.2 logMAR or transition to off-chart) in best-corrected visual acuity (BCVA) were 3.4 times higher in the idebenone group compared to the NH control group, reinforcing the clinical relevance of the treatment effect.​ The most common adverse reactions (incidence ≥3%) are increase of alanine aminotransferase, diarrhea, and increase in aspartate aminotransferase.​

These events were generally mild to moderate, reversible, and rarely required treatment discontinuation.

About Chiesi Group

Chiesi is a research-oriented international biopharmaceutical group that develops and markets innovative therapeutic solutions in respiratory health, rare diseases, and specialty care. The company’s mission is to improve people’s quality of life and act responsibly towards both the community and the environment.

By changing its legal status to a Benefit Corporation in Italy, the US, France and Colombia, Chiesi’s commitment to creating shared value for society as a whole is legally binding and central to company-wide decision-making. As a certified B Corp since 2019, Chiesi is part of a global community of businesses that meet high standards of social and environmental impact. The company aims to reach Net-Zero greenhouse gases (GHG) emissions by 2035.
With 90 years of experience, Chiesi is headquartered in Parma (Italy), with 31 affiliates worldwide, and counts more than 7,500 employees. The Group’s research and development center in Parma works alongside 6 other important R&D hubs in France, the US, Canada, China, the UK, and Sweden.
For more information visit www.chiesi.com.

About Chiesi Global Rare Diseases
Chiesi Global Rare Diseases is a business unit of the Chiesi Group established to deliver innovative therapies and solutions for people living with rare diseases. As a family business, Chiesi Group strives to create a world where it is common to have therapy for all diseases and acts as a force for good, for society and the planet. The goal of the Global Rare Diseases unit is to ensure equal access so as many people as possible can experience their most fulfilling life. The unit collaborates with the rare disease community around the globe to bring voice to underserved people in the health care system.

For more information visit www.chiesirarediseases.com.

Follow @ChiesiGlobalRareDiseases on LinkedIn, Facebook, Instagram, X and YouTube.

Chiesi Global Rare Diseases Media Contact
Sky Striar
LifeSci Communications
Email: sstriar@lifescicomms.com

References

1. NHS England (July 2020). “Idebenone for treating people over 12 years of age with Leber’s Hereditary Optic Neuropathy”. Available at: https://www.england.nhs.uk/wp-content/uploads/2020/07/Idebenone-for-treating-people-over-12-years-of-age-with-LHO-Neuropathy.pdf
2. Preserving/protecting/reactivating retinal ganglion cell (RGC) function mitochondrial dysfunction: use: Haefeli RH, Erb M, et al. NQO1Dependent Redox Cycling of Idebenone: Effects on Cellular Redox Potential and Energy Levels. PLoS One. 2011;6(3):e17963. 
3. Klopstock T, Yu-Wai-Man P, et al. (RHODOS Trial) A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy. Brain. 2011;134(9):2677–2686.
4. Yu-Wai-Man P, Carelli V, Newman NJ, Klopstock T, LEROS Study Group. (LEROS) Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial. Cell Reports Medicine. 2024;5(3):101437.
5. Catarino CB, von Livonius B, et al. (Expanded Access Program) Real-World Clinical Experience With Idebenone in the Treatment of LHON. J Neuro-Ophthalmol. 2020;40(4):558–565.
6. Feng Z, Nadikudi M, Woolley KL, Hemasa AL, Chear S, Smith JA, Gueven N. Bioactivity Profiles of Cytoprotective Short-Chain Quinones. Molecules. 2021 Mar 4;26(5):1382. doi: 10.3390/molecules26051382. PMID: 33806577; PMCID: PMC7961879.
7. Carelli V et al. European Ophthalmic Review. 2019;13(Suppl 2). https://www.touchophthalmology.com/lebers-hereditary-optic-neuropathy-a-global-perspective/ 
8. Poincenot, Lissa et al. (May 2020). “Demographics of a Large International Population of Patients Affected by Leber’s Hereditary Optic Neuropathy”. Available at: https://www.aaojournal.org/article/S0161-6420(19)32295-X/fulltext 

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