Tocilizumab Approved by the FDA for Systemic Sclerosis-Associated Interstitial Lung Disease

Genentech announced that tocilizumab (Actemra) was approved by the US Food and Drug Administration (FDA) for treatment of systemic sclerosis (SSc)-induced interstitial lung disease (ILD). SSc, also known as scleroderma, is a progressive and incurable autoimmune disease that causes the tissues of the skin and lugs to thicken and harden and currently impacts up to 75,000 people in the United States. Of these patients, roughly 80% are affected by ILD, a life-threatening condition that greatly impacts lung function.

Tocilizumab was originally marketed as the first humanized interleukin-6 (IL-6) receptor antagonist for patients with rheumatoid arthritis who had inadequate reaction to disease-modifying antirheumatic drugs (DMARDs).

Subcutaneous injection of tocilizumab has been shown to improve the rate of lung function in patients with SSc-ILD when compared with a placebo. Tocilizumab was the first biologic therapy approved by the FDA for the treatment of this disease. The focuSSced trail was a phase 3 randomized, double-blind, placebo-controlled clinical trial consisting of 212 adults with SSc. While the trial did not meet its primary endpoint of changes from baseline to week 48 in the modified Rodnan Skin Score (mRSS), the standard measure for skin fibrosis, patients receiving tocilizumab showed less of a decline in observed forced vital capacity (FVC), a standard measure of lung function. The FVC, a secondary endpoint, assessed air exhaled and percent-predicted forced vital capacity (ppFVC), which compares the score of a patient with SSc-ILD with those of a healthy person of the same characteristics such as age, gender, race, and height.

Patients were randomized in a 1:1 ratio to receive either 162 mg of tocilizumab or a placebo for 48 weeks, followed by open-label tocilizumab for an additional 48 weeks. During the trial, 68 patients (65%) receiving tocilizumab and 68 patients (64%) receiving the placebo had SSc-ILD. Post-hoc analyses evaluated the results of both patient cohorts with and without SSc-ILD. FVC results demonstrate the effectiveness of tocilizumab in regard to reducing progressive loss of function for patients with SSc-ILD. However, investigators caution that as the primary endpoint of mRSS was not achieved, the FVC results should be interpreted with caution and may be misleading.

In the SSc-ILD subgroup, patients receiving tocilizumab had a smaller decline in ppFVC scores (0.07% vs. -6.4%, mean difference 6.47%) as well has FVC scores (mean change -14 mL vs. -255 mL, mean difference 241 mL). Mean change throughout the study for mRSS was -5.88 for patients receiving tocilizumab versus -3.77 for patients taking the placebo. The most common adverse event for patients receiving subcutaneous tocilizumab was infection.

Tocilizumab was granted Priority Review by the FDA, which is designated for medicines that that may provide significant improvements in the treatment, prevention, or diagnosis of a disease. “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,” stated Levi Garraway, MD, PhD, chief medical officer, and head of Global Product Development.