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, a Rare, Debilitating Condition

Rhea-AI Summary

Genentech announced FDA approval for Actemra® (tocilizumab) subcutaneous injection to slow pulmonary function decline in adults with systemic sclerosis-associated interstitial lung disease (SSc-ILD). This marks the first biologic therapy approved for this condition, impacting approximately 75,000 patients in the U.S. Key findings from the focuSSced Phase III trial indicated that Actemra reduced lung function decline compared to placebo, although the primary endpoint related to skin fibrosis was not met.

Common side effects included infections, aligning with Actemra's known safety profile.

Positive

• FDA approved Actemra as the first biologic therapy for SSc-ILD.
• In clinical trials, Actemra showed a reduced decline in lung function compared to placebo in SSc-ILD patients.

Negative

• The focuSSced trial did not meet its primary endpoint regarding skin fibrosis (mRSS).
• Statistical significance for the primary endpoint of mRSS was not achieved in the faSScinate trial.

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) approved 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. Actemra is the first biologic therapy approved by the FDA for the treatment of the disease.

Systemic sclerosis (SSc), 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 (ILD), which may occur in approximately 80% of SSc patients, causes inflammation and scarring of the lungs and can be life-threatening.

“We are honored to offer the very first FDA-approved biologic treatment option to people living with systemic sclerosis-associated interstitial lung disease,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “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 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 (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%) in the Actemra arm and 68 patients (64%) 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 (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.

About the focuSSced Trial

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 (65%) in the Actemra arm and 68 patients (64%) 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. 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.

About Actemra

Actemra was the first humanized interleukin-6 (IL-6) receptor antagonist approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have used one or more disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX), 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 (GCA), for the treatment of patients two years of age and older with active polyarticular juvenile idiopathic arthritis (PJIA) or active systemic juvenile idiopathic arthritis (SJIA), 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 (CRS). 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.

Actemra is intended for use under the guidance of a healthcare practitioner.

Important Safety Information

Actemra can cause serious side effects. Actemra changes the way a patient’s immune system works. This can make a patient more likely to get infections or make any current infection worse. Some people taking Actemra have died from these infections.

Actemra can cause other serious side effects. These include:

• Tears of the stomach or intestines
• Liver problems (hepatotoxicity)
• Changes in blood test results, including low neutrophil (white blood cells) and platelet (platelets help the blood to clot) counts, and increases in certain liver function test levels and blood cholesterol levels
• An increased risk of certain cancers by changing the way a patient’s immune system works
• Hepatitis B infection
• Serious allergic reactions, including death. These may happen with Actemra infusions or injections, even if they did not occur with an earlier infusion or injection. If a patient has had hives, a rash, or experienced flushing after injecting, the patient should tell their doctor or nurse before their next injection
• Nervous system problems

Patients should not receive Actemra if they are allergic to Actemra or if they have had a bad reaction to Actemra previously.

Most common side effects in patients treated with Actemra:

Patients should tell their doctor if they have these or any other side effect that bothers them or does not go away:

• Upper respiratory tract infections (like common cold and sinus infections)
• Headache
• Increased blood pressure (also called hypertension)
• Injection site reactions

Actemra & pregnancy:

Patients should tell their doctor if they are planning to become pregnant, are pregnant, plan to breastfeed, or are breastfeeding. The patient and their doctor should decide if the patient will take Actemra or breastfeed. Patients should not do both. If a patient is pregnant and taking Actemra, they should join the pregnancy registry. To learn more, patients should call 1-877-311-8972 or talk to their doctor to register.

Patients should tell their doctor right away if they are experiencing any side effects. Report side effects to the FDA at 1-800-FDA-1088 or http://www.FDA.gov/medwatch. Report side effects to Genentech at 1-888-835-2555.

Please visit http://www.actemra.com for the full Prescribing Information, including Boxed Warning and Medication Guide, for additional Important Safety Information or call 1-800-ACTEMRA (228-3672).

About Genentech Access Solutions

Access Solutions is part of Genentech’s commitment to helping people access the Genentech medicines they are prescribed, regardless of their ability to pay. The team of in-house specialists at Access Solutions is dedicated to helping people navigate the access and reimbursement process and to providing assistance to eligible patients in the United States who are uninsured or cannot afford the out-of-pocket costs for their medicine. To date, the team has helped more than 2 million patients access the medicines they need. Please contact Access Solutions (866) 4ACCESS/(866) 422-2377 or visit http://www.Genentech-Access.com for more information.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20210304006148/en/

FAQ

What is Actemra approved for by the FDA?

Actemra is FDA approved for slowing the decline of pulmonary function in adults with systemic sclerosis-associated interstitial lung disease (SSc-ILD).

When did the FDA approve Actemra for SSc-ILD?

The FDA approved Actemra for SSc-ILD as of the announcement date of the press release.

What were the results of the focuSSced trial for Actemra?

The focuSSced trial showed that Actemra reduced lung function decline compared to placebo for patients with SSc-ILD but did not meet the primary endpoint regarding skin fibrosis.

What is the stock symbol for Genentech and Roche?

Genentech is part of the Roche Group, whose stock symbols are SIX: RO, ROG; OTCQX: RHHBY.