FDA issues complete response letter for idebenone in LHON

Chiesi Global Rare Diseases announced that the FDA has issued a complete response letter (CRL) regarding its new drug application (NDA) for idebenone for the treatment of Leber hereditary optic neuropathy (LHON), a rare mitochondrial disease that causes rapid and severe vision loss.^1,2

According to the company, the agency’s decision means that additional information will be required before the application can be reconsidered.¹

Idebenone had previously been under FDA priority review, with a target action date of February 28, 2026. The therapy was being evaluated as a potential treatment for LHON, a condition characterized by sudden vision loss due to mitochondrial dysfunction affecting retinal ganglion cells.^3,4

In its statement, Chiesi said the FDA’s CRL relates to the NDA for idebenone in LHON and outlines issues that must be addressed before approval can be granted. The company indicated it is reviewing the contents of the letter and plans to work with the agency to determine appropriate next steps for the application.¹

The NDA was supported by data from two studies. The pivotal RHODOS trial was a randomized, double-blind, placebo-controlled study evaluating idebenone in adolescents and adults with LHON. Additionally, the Phase 4 LEROS open-label interventional study assessed the safety and efficacy of idebenone across primary mitochondrial DNA mutations in the same patient population.^1,3,4

LHON is a rare inherited disorder that leads to acute or subacute central vision loss, often affecting young adults. There are currently no FDA-approved treatments for LHON in the United States, although idebenone has been authorized in other regions.^3,4

The company did not specify in the announcement the exact nature of the deficiencies cited by the FDA but confirmed that the CRL requires further data. External reports indicated that the agency may be seeking additional clinical evidence to support the application.^1,2

Chiesi noted that it remains committed to advancing idebenone for patients with LHON and intends to engage with the FDA to address the agency’s feedback. The company did not provide a timeline for resubmission or additional studies.¹

References

1. FDA issues a complete response letter (CRL) regarding the NDA for idebenone for Leber hereditary optic neuropathy (LHON) in the United States. News release. Chiesi Global Rare Diseases. March 5, 2026. Accessed March 17, 2026. https://chiesirarediseases.com/media/20260305-fda-issues-a-complete-response-letter-crl-regarding-the-nda-for-idebenone-for-leber-hereditary-optic-neuropathy-lhon

2. Crabbe J. US FDA rejects Chiesi’s idebenone for LHON, asks for more clinical data. Market Scope. March 13, 2026. Accessed March 17, 2026. https://www.market-scope.com/pages/news/9014/us-fda-rejects-chiesi-s-idebenone-for-lhon-asks-for-more-clinical-data

3. Idebenone accepted by FDA for priority review for Leber hereditary optic neuropathy (LHON). Published September 22, 2025. Accessed September 22, 2025. https://chiesirarediseases.com/media/20250922-idebenone-accepted-by-fda-for-priority-review-for-leber-hereditary-optic-neuropathy-lhon

4. Harp MD. Idebenone accepted by FDA for priority review. Ophthalmology Times. September 22, 2025. Accessed March 17, 2026. https://www.ophthalmologytimes.com/view/idebenone-accepted-by-fda-for-priority-review-for-leber-hereditary-optic-neuropathy