Interferon gamma, or IFN-gamma, is a naturally occurring protein that plays an important role in immune response.

The U.S. Food and Drug Administration has approved the protein under the brand name Actimmune to treat two rare diseases, one that affects immune cells and another that affects bone formation. Those conditions are chronic granulomatous disease and severe malignant osteoporosis.

Horizon Pharma, which makes IFN-gamma, is now investigating the drug as a potential treatment for people with Friedreich’s ataxia, or FA.

How Actimmune works

The genetic defect in FA confuses the DNA code responsible for guiding the production of frataxin, a protein found in energy-producing cell components called mitochondria. The nerve damage that occurs in FA is related to the low levels of frataxin. This means that increasing the amount of frataxin in cells may help prevent or slow the progression of the disease.

IFN-gamma was first recognized as a potential therapy when scientists discovered that it increased frataxin levels in mice with FA and in cells obtained from people with the disease. The scientists thought IFN-gamma might increase the transcription of the gene that codes for frataxin. Transcription is the process under which a DNA code is transferred to messenger RNA, which then oversees the formation of a protein. Increasing the transcription of the frataxin gene increases the amount of frataxin protein that cells produce.

Actimmune in clinical trials

The positive results from the animal and laboratory studies, published in the scientific journal Human Molecular Genetics in 2012, led to multiple clinical trials on whether Acimmune could increase frataxin levels in humans.

One trial (NCT01965327) was sponsored by the Children’s Hospital of Philadelphia in collaboration with the Friedreich’s Ataxia Research Alliance and Vidara Therapeutics, Horizon Pharma has since acquired.

The results of the trial, published in Acta Neurologica Scandinavica in 2015, were mixed: Researchers found increases in frataxin levels in some types of cells, but not in others.

A decided plus was that scores on a measure of FA function — the Friedreich’s Ataxia Rating Scale, or FARS — improved significantly, although the trial was not placebo-controlled.

After the study’s encouraging results, Horizon Pharma committed to continue exploring Actimmune as an FA treatment. It obtained FDA fast-track status for Actimmune as an FA therapy. This will accelerate the approval process if clinical trials continue to show positive results.

In June 2015 Horizon Pharma announced a Phase 3 placebo-controlled trial (NCT02415127) to evaluate the safety and effectiveness of Actimmune in FA.

Participants in the STEADFAST trial were randomized to receive either injections of Actimmune or a placebo three times a week under the skin for 26 weeks. Horizon increased the dose of the drug during the first four weeks.

The measures of effectiveness that researchers used included changes in patients’ FARS scores and timed walking tests, and number of adverse events. The study has been completed but the results have yet to be  released.

An open-label Phase 3 long-term safety extension study (NCT02797080) of Actimmune as an FA treatment began enrolling participants who had completed the initial Phase 3 trial in late 2016.  Results of that study also have yet to be announced.

Additional information

Some of the most common side effects of Actiummune, based on its use for other conditions, include flu-like symptoms such as fever, chills, and aches.

Actiummune should be used with caution in people who have heart disease, seizure disorders, or some blood disorders, Horizon cautions.

Note: Friedreich’s Ataxia News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.