Therapy Areas: Autoimmune
Genentech's Actemra Becomes the First Biologic Therapy Approved by the FDA for Slowing the Rate of Decline in Pulmonary Function in Adults with Systemic Sclerosis-Associated Interstitial Lung Disease
8 March 2021 - - The US Food and Drug Administration approved US-based biotechnology company Genentech's Actemra (tocilizumab) subcutaneous injection for slowing the rate of decline in pulmonary function in adult patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), a debilitating condition with limited treatment options, the company said.

Actemra is the first biologic therapy approved by the FDA for the treatment of the disease.

Genentech a member of the Roche Group (SIX: RO) (OTCQX: RHHBY).

Systemic sclerosis, also known as scleroderma, is an often devastating autoimmune disease that 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, which may occur in approximately 80% of SSc patients, causes inflammation and scarring of the lungs and can be life-threatening.

The FDA approval is based on data from the focuSSced trial, a Phase III randomized, double-blind, placebo-controlled clinical trial of 212 adults with systemic sclerosis. Supportive information was also used from the faSScinate trial, a Phase II/III, 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, 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, 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 in the Actemra arm and 68 patients in the placebo arm had SSc-ILD at baseline, as confirmed by a visual read of high resolution computed tomograph 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 (0.07% vs. -6.4%, mean difference 6.47%), and a smaller decline in FVC compared to 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 compared to placebo was -5.88 vs. -3.77, mean difference -2.11.

The safety profile for Actemra through week 48 in the focuSSced study was comparable for SSc-ILD and SSc patients overall, and in both focuSSced and faSScinate studies was consistent with the known safety profile of Actemra.

The most common adverse events in patients treated with Actemra were infections.
Actemra was previously granted Priority Review for this condition by the FDA.

This designation is 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.

The focuSSced (NCT02453256) study was a Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial to assess the efficacy and safety of Actemra versus placebo in people living with systemic sclerosis.

Patients were randomized in a 1: 1 ratio to receive weekly subcutaneous injections of 162 mg of Actemra or placebo during the 48-week, double-blinded, placebo-controlled period, followed by open-label Actemra 162 mg administered subcutaneously every week for another 48 weeks.

Rescue treatment was allowed during the treatment period after 16 weeks for >10% ppFVC decline or after 24 weeks for worsening skin fibrosis.

The primary efficacy endpoint was change from baseline at week 48 in mRSS. Change from baseline in FVC at week 48 was a key secondary endpoint.

Of the 212 patients who were randomized, 68 patients in the Actemra arm and 68 patients in the placebo arm had SSc-ILD at baseline, as confirmed by a visual read of high resolution computed tomograph by blinded thoracic radiologists.

The mean ppFVC at baseline for patients with SSc-ILD identified by HRCT was 79.6% (median 80.5%).

Post-hoc analyses were performed to evaluate results within the subgroups of patients with and without SSc-ILD.

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.

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.

Actemra was the first humanized interleukin-6 receptor antagonist approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have used one or more disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, that did not provide enough relief.

The extensive Actemra RA IV clinical development program included five Phase III clinical studies and enrolled more than 4,000 people with RA in 41 countries.

The Actemra RA subcutaneous clinical development program included two Phase III clinical studies and enrolled more than 1,800 people with RA in 33 countries.

Actemra subcutaneous injection is also approved for the treatment of adult patients with giant cell arteritis, for the treatment of patients two years of age and older with active polyarticular juvenile idiopathic arthritis or active systemic juvenile idiopathic arthritis, and for slowing the rate of decline in pulmonary function in adult patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).

In addition, Actemra is also approved in the IV formulation for patients two years of age and older with active PJIA, SJIA or CAR T cell-induced cytokine release syndrome.

Actemra is not approved for subcutaneous use in people with CRS. It is not known if Actemra is safe and effective in children with PJIA, SJIA or CRS under two years of age or in children with conditions other than PJIA, SJIA or CRS.
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