IFN-gamma Leads to Some Improvements for FA Patients in Turkish Study

Six months of treatment with interferon-gamma, known as IFN-gamma, is safe and leads to significant improvements in walking skills and stance in people with Friedreich’s ataxia (FA), according to a small study in Turkey.

However, no significant improvements were observed in other areas of motor coordination, such as sitting, upper body movement, and speech.

Still, the observed modest benefits are in contrast with previous Phase 3 trial data showing that the therapy failed to significantly delay or halt disease progression in FA patients.

Further studies are needed to assess the potential long-term benefits of the therapy, the researchers said.

The study, “Efficacy and Tolerability of Interferon Gamma in Treatment of Friedreich’s Ataxia: Retrospective Study,” was published in the journal Archives of Neuropsychiatry.

A small signaling molecule, IFN-gamma is involved in immune reactions and iron metabolism, which is abnormal in FA. Marketed by Horizon Pharma under the brand name Actimmune, IFN-gamma treatment is approved in the U.S. for two rare diseases affecting either immune cells or bone formation.

Such treatments were shown in a previous study to increase the levels of frataxin, the protein missing in FA patients, in a mouse model of FA and in cells from patients. That prompted the launch of clinical trials testing the therapy in people with FA.

An open-label Phase 2 trial (NCT01965327) then found that IFN-gamma, given through an under-the-skin (subcutaneous) injection every three weeks, was well-tolerated and resulted in significant reductions in disease severity. Of note, disease severity was assessed with the Friedreich Ataxia Rating Scale (FARS).

FARS combines timed measures of performance, functional disability staging, a patient-reported outcome of activities of daily living, and a neurologic exam.

However, the subsequent Horizon-sponsored, placebo-controlled STEADFAST Phase 3 trial (NCT02415127) failed to meet its main and secondary goals.

Specifically, after six months, children and adults with FA receiving IFN-gamma showed no significant changes in disease severity (measured with the modified FARS), motor function, ability to perform activities of daily living, and quality of life, compared with those given a placebo.

Notably, during STEADFAST’s open-label extension study (NCT02593773), in which all trial participants received IFN-gamma, the absolute values of the modified FARS were better than those from natural history studies. The rate of disease progression also was slightly slower.

Still, the lack of pronounced benefits with IFN-gamma led to Horizon’s discontinuation of Actimmune’s clinical development for FA.

Now, researchers at the Faculty of Medicine of Erciyes University, in Turkey, have launched their own research into IFN-gamma. Their study described the safety and effectiveness of the therapy in 14 FA patients — 10 females and four males — followed at their University hospital.

“To the best of our knowledge, this is the first study made conducted in our country to evaluate the effect of IFN gamma on this patient group,” the researchers wrote.

The team retrospectively analyzed the patients’ demographic information, clinical and laboratory data prior to treatment, and after three and six months of treatment, and the occurrence of treatment-related adverse events (side effects).

Neurologic status was assessed with the Scale for the Assessment and Rating of Ataxia (SARA), which looks at problems in motor coordination in several areas, such as walking, standing, sitting, speaking, and upper and lower body movements.

With a mean age of 29.6, these patients had been living with an FA diagnosis for a mean of 9.4 years. Among them, 11 were being treated with idebenone, an experimental antioxidant therapy commonly used off-label for treating FA.

The patients received IFN-gamma for a mean of 7.2 months.

The results showed that the therapy led to significant improvements in patients’ walking skills after three months, which were sustained at six months. Stance, or the way in which someone stands, also was significantly improved after six months of treatment.

No significant changes were observed in the remaining motor domains assessed with SARA.

Ten individuals (71.4%) experienced therapy-induced flu-like symptoms, one of the most common side effects of IFN-gamma. Most of these reactions were reported as being mild in severity. Two people discontinued treatment between the three- and six-month assessment due to therapy ineffectiveness or patient incompatibility.

These findings suggested that IFN-gamma is “a well-tolerated and partially effective treatment option in the treatment of [FA],” the researchers wrote, adding that further studies are needed to better determine the therapy’s long-term effects.