FDA approves Actemra, first biologic for SSc-related interstitial lung disease
The FDA has approved subcutaneous tocilizumab to curb the rate of progressive loss of lung function among adults with systemic sclerosis-associated interstitial lung disease, according to a press release from Genentech.
Previously approved in the United States for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis and giant cell arteritis, Actemra (tocilizumab) is the first biologic authorized to treat SSc-related interstitial lung disease.
“We are honored to offer the very first FDA-approved biologic treatment option to people living with systemic sclerosis-associated interstitial lung disease,” Levi Garraway, MD, PhD, chief medical officer and head of global product development for Genentech, said in the release. “We worked closely with the FDA to evaluate Actemra’s impact on lung function in this setting. This milestone approval provides a much-needed new treatment option for people living with this rare, debilitating disease.”
The FDA based its approval on results from the focuSSced trial, a phase 3, randomized, placebo-double-blind, controlled, 48-week study — with ancillary data from the faSScinate trial, a phase 2/3 randomized, double-blind, placebo-controlled study — to evaluate efficacy and safety of Actemra for patients with systemic sclerosis. A total of 212 adults with systemic sclerosis were randomized 1-to-1 to receive either weekly subcutaneous injections of 162 mg of Actemra or placebo, followed by open-label Actemra 162 mg administered weekly for another 48 weeks.
Although the focuSSced trial failed to meet its primary endpoint of change from baseline to week 48 in the modified Rodnan Skin Score (mRSS), with similar shortcomings observed in the faSScinate trial, both trials demonstrated that patients treated with Actemra demonstrated less decline in observed forced vital capacity (FVC) and percent predicted FVC (ppFVC), driven primarily by patients in the SSc-related interstitial lung disease subset.
In this subgroup, patients treated with Actemra had a smaller decline in mean ppFVC vs. patients on placebo (0.07% vs. -6.4%, mean difference 6.47%), and a smaller decline in FVC vs. placebo (mean change -14 mL vs. -255 mL, mean difference 241 mL). The mean change from baseline to week 48 in mRSS in patients receiving Actemra vs. placebo was -5.88 vs. -3.77, mean difference -2.11.
“The results of the key FVC secondary endpoints support the effectiveness of Actemra in reducing the rate of progressive loss of lung function in SSc-ILD patients,” noted the press release. “However, as the trial did not provide evidence of an effect on the primary endpoint of mRSS, the estimated magnitude of effect on the FVC endpoints should be interpreted with caution and comparisons to results of other products and studies may be misleading.”
The focuSSced study demonstrated that Actemra’s safety profile through week 48 was comparable for both patients with SSc-related interstitial lung disease and SSc. The most common adverse reactions in both the focuSSced and faSScinate studies — consistent with the established safety profile for tocilizumab — included diarrhea, headache, nasopharyngitis and upper respiratory tract infections, as well as reports of increased risk for serious infections.