DISCONTINUED: Stages of Development for Nicotinamide

The drug development process can be thought of as a series of stages, and drugs must successfully pass through each stage to become available to patients. This treatment has been evaluated, and the program has been discontinued. Thus, it is not in the pipeline.

Link to previous study

Treatment with nicotinamide resulted in an upregulation of frataxin mRNA and protein in lymphoblastoid cell lines derived from FA patients, in patients PBMC and in the YG8 mouse model. This effect is concomitant with a reduced DNA methylation, a reduction in histone H3K9 and H3K27 methylation and an increase in histone H3 and H4 acetylation in the FXN gene. Nicotinamide also restored the expression of several genes known to be dysregulated in frataxin deficient cells.

2012: An open-label pilot study, evaluating dosage, safety and biochemical and clinical outcomes in individuals with FA was launched in London, England.

The investigators reported that at higher doses (>3.5 grams per day of nicotinamide) there were issues with tolerability (e.g., nausea) and safety (elevated liver enzymes).

At lower doses the drug was well tolerated. An increase in frataxin protein was observed with single oral dosing in a Phase I portion of the study, and a sustained increase in frataxin gene expression and protein with daily dosing over eight weeks was observed in the Phase II portion of the study.

No clinical benefit or improvement was observed.

2017: A multinational study was approved and funded by the European Union, E-Rare-3 Project. NICOFA, Nicotinamide for the treatment of Friedreich ataxia, was a randomized, placebo-controlled and double-blinded study evaluating the efficacy of high-dose nicotinamide in FA over 2 years. Study sites were planned for Germany, Spain, Austria, Italy and France. See additional amendments to the study, below.

May 2019: Change of sponsor representative, extension of IMP expiry to 9 months, change of personal at trial site.

May 2020: Substantial Amendment 02 in Germany. Delay of recruitment start due to COVID-19 pandemic.

June 2020: Substantial Amendment 03 in Germany. Start of recruitment, extension of IMP expiry to 13 months, update of Investigator’s Brochure (version 03).

February 2022: Substantial Amendment 04 in Germany. Stop of recruitment 02.05.2022.