FDA Approves Genentech’s Actemra to Slow Decline in Pulmonary Function in Adults with SSc

Rare Daily Staff

The U.S. Food and Drug Administration approved Roche subsidiary Genentech’s Actemra to slow the rate of decline in pulmonary function in adult patients with the rare autoimmune condition systemic sclerosis-associated interstitial lung disease.

Systemic sclerosis (SSc), also known as scleroderma, often worsens over time and has no cure. It occurs when the immune system malfunctions causing tissues of the skin and lungs to thicken and harden. SSc impacts up to 75,000 people in the United States. Interstitial lung disease (ILD), which may occur in approximately 80 percent of SSc patients, causes inflammation and scarring of the lungs and can be life-threatening.

Actemra, a humanized interleukin-6 receptor antagonist, is the first FDA-approved biologic treatment option for people living with systemic sclerosis-associated interstitial lung disease. “We worked closely with the FDA to evaluate Actemra’s impact on lung function in this setting,” said Levi Garraway, chief medical officer and head of Global Product Development. This milestone approval provides a much-needed new treatment option for people living with this rare, debilitating disease.”

The FDA approval is based on data from the focuSSced trial, a phase 3 randomized, double-blind, placebo-controlled clinical trial of 212 adults with systemic sclerosis. Supportive information was also used from the faSScinate trial, a phase 2/3, randomized, double-blind, placebo-controlled study in patients with SSc. The focuSSced trial did not meet its primary endpoint of change from baseline to week 48 in the modified Rodnan Skin Score (mRSS), which is a standard outcome measure for skin fibrosis (the scarring or hardening of the skin) in SSc. There also was not a statistically significant effect on the primary endpoint of mRSS in the faSScinate trial.

However, in the overall population of the focuSSced study, patients treated with Actemra, as compared to placebo-treated patients, were observed to have less decline from baseline to week 48 in observed forced vital capacity (FVC), a common measure of lung function that assesses how much air can be exhaled, and percent predicted forced vital capacity (ppFVC), which compares the observed FVC to that expected for a healthy person of the same age, gender, race and height. FVC results were similar in the faSScinate study.

Of the 212 patients who were randomized into the focuSSced study, 68 patients (65 percent) in the Actemra arm and 68 patients (64 percent) in the placebo arm had SSc-ILD at baseline, as confirmed by a visual read of high resolution computed tomograph (HRCT) by blinded thoracic radiologists. Post-hoc exploratory analyses were performed to evaluate the results within the subgroups of patients with and without SSc-ILD. The ppFVC and FVC results in the overall population were primarily driven by results in the SSc-ILD subgroup. In that subgroup, patients in the Actemra group had a smaller decline in mean ppFVC than patients on placebo (mean difference 6.47 percent), and a smaller decline in FVC compared to placebo (mean difference 241 mL). The mean change from baseline to week 48 in mRSS in patients receiving Actemra compared to placebo was -5.88 vs. -3.77, mean difference -2.11.

The most common adverse events in patients treated with Actemra were infections.

Actemra was previously granted Priority Review for this condition by the FDA, a designation given to medicines that have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. This is the sixth FDA approved indication for Actemra since the medicine was launched in the United States in 2010.

Photo: Levi Garraway, chief medical officer and head of Global Product Development