Roche Receives FDA Breakthrough Therapy Designation, Initiaties New Study For SSc/RA Therapy ACTEMRA/RoACTEMRA

Roche Receives FDA Breakthrough Therapy Designation, Initiaties New Study For SSc/RA Therapy ACTEMRA/RoACTEMRA

Basel, Switzerland based multinational pharma giant Roche has been granted breakthrough therapy designation (BTD) status by the U.S. Food and Drug Administration (FDA) for its ACTEMRA/RoACTEMRA (tocilizumab) drugs for treatment of systemic sclerosis (SSc). The BTD designation is granted to expedite development and review of medicines intended to treat serious diseases, and to help ensure patients have access to them as soon as possible.

Roche has also initiated a global Phase 3 study in SSc (NCT02453256), in addition, new data from the U-ACT-EARLY and TENDER studies in patients with early rheumatoid arthritis (RA) and systemic juvenile idiopathic arthritis (sJIA), respectively, as well as results from the Phase 2 fascinate study in SSc5 were presented last week at the annual congress of the European League Against Rheumatism (EULAR 2015) that was held in Rome from 10 through 13 June.

Roche reports that close to 500,000 people worldwide have benefited from treatment with ACTEMRA/RoACTEMRA since the drug’s initial approval over a decade ago. “The breadth of our study results at EULAR, ranging from arthritis in adults and children to a rare inflammatory disorder, underscores our commitment to helping people with debilitating autoimmune diseases,” says Sandra Horning, M.D., Roches Head of Global Product Development and Chief Medical Officer. “These new data further demonstrate the efficacy and safety of ACTEMRA/RoACTEMRA in multiple diseases, including use as a single therapy in early RA.”


Roche states that ACTEMRA/RoACTEMRA has been proven to help people with RA protect against joint damage and to have better quality of life, citing clinical research showing that effective treatment during the the disease’s early phase may prevent irreversible damage to joints and long-term disability.

In patients who had been diagnosed less than a year prior to study enrolment with no history of any previous disease-modifying therapy, ACTEMRA/RoACTEMRA nearly doubled sustained remission (SR) rates with comparable results as monotherapy and combination. SR rates were 84% for ACTEMRA/RoACTEMRA monotherapy, 86% for ACTEMRA/RoACTEMRA + methotrexate (MTX), and 44% for MTX alone.1 Median time to SR was seen in just over two months: 9.9 weeks for ACTEMRA/RoACTEMRA + MTX and 12.7 weeks for ACTEMRA/RoACTEMRA monotherapy (MTX alone results were not measurable).1 The safety profile was comparable with previously reported data.1 Full results from the U-ACT-EARLY study were reported: in an oral presentation at EULAR 2015 on Thursday, 11 June, 2015).1

ACTEMRA/RoACTEMRA in systemic juvenile idiopathic arthritis (sJIA)

Juvenile idiopathic arthritis (JIA) affects approximately 100 in every 100,000 children10 — 10 to 20 percent of which will be cases of sJIA — a rare and severe form of childhood arthritis. sJIA is characterised by inflammatory arthritis accompanied by intermittent fever, skin rash, anaemia, enlargement of the liver and/or spleen and inflammation of the lining of the heart and/or lungs. The peak age of onset of sJIA is between 18 months and two years, although persistence of the disease into adulthood occurs. sJIA has the worst long-term prognosis of all childhood arthritis subtypes, accounting for almost two-thirds of all deaths among children with arthritis, with an overall mortality rate estimated to be between two to four percent. Treatment with high dose corticosteroids does not improve the long-term prognosis is often accompanied by severe side effects.

The the global phase III TENDER study conducted at approximately 70 centres in 20 countries demonstrated that ACTEMRA was effective in improving signs and symptoms of sJIA, with 97 percent of patients achieved 30 percent improvement in their disease symptoms (JIA ACR30) and 64 percent achieving 90 percent improvement (JIA ACR90).2

Further TENDER data showed 70 percent of patients on ACTEMRA achieved JIA ACR70+ and 37 percent achieved JIA ACR90+, compared to eight percent and five percent of patients who received placebo, respectively. In addition to the significant improvement in JIA ACR response, nearly two-thirds of patients in the study were free of rash after three months. In the study, ACTEMRA was well tolerated in children with sJIA, with a safety profile similar to adults treated with ACTEMRA for rheumatoid arthritis (RA).

ACTEMRA/RoACTEMRA’s efficacy was maintained through week 260 (4.9 years) with no change in the observed safety profile.2 Full results were displayed in a poster presentation at EULAR 2015 on Thursday, 11 June, 2015. 2 ACTEMRA/RoACTEMRA is the only agent approved for the treatment of both sJIA and polyarticular juvenile idiopathic arthritis (pJIA) in patients two years and older.12

ACTEMRA/RoACTEMRA in systemic sclerosis (SSc)

Systemic sclerosis (SSc) is a rare, debilitating, chronic autoimmune disorder characterized by blood vessel abnormalities, as well as degenerative changes and scarring in the skin, joints, and internal organs.13 In SSc, something causes the body’s immune system to attack its own tissue. The underlying cause is unknown and SSc is potentially fatal. There are two main types, limited cutaneous and diffuse cutaneous. When it affects the skin, it can cause the skin—most commonly on the hands and/or face—to harden. With the blood vessels, it can cause Raynaud’s, and when it affects the internal organs, it may cause disability or even death.

Incidence of SSc is difficult to measure, but the disease is estimated to affect approximately 2.5 million people worldwide, and it has the highest mortality of any rheumatic disease.3,14

The FDA BTD status for ACTEMRA/RoACTEMRA was granted based on data from the Phase 2 faSScinate study. Forty-eight weeks of data from the faSScinate study were summarized an the oral presentation at EULAR 2015. While the primary endpoint of improvement in skin thickening at 24 weeks, as assessed by Rodnan skin score, was not met, Roche reports that a meaningful trend was observed in the second part of the study, in which continued improvement in skin thickening between weeks 24 and 48.5 was observed. 5 Extent and severity of skin thickness in SSd correlates to disease worsening, increased disability, and decreased survival.15,16 Based on these Phase 2 results and the unmet need in patients with SSc, for which there are no approved disease modifying therapeutic options, Roche has initiated a global Phase 3 multicentre, randomized, double-blind, placebo-controlled study (NCT02453256).

RoACTEMRA/ACTEMRA (tocilizumab)

Roche describes ACTEMRA/RoACTEMRA as the first anti-IL-6 receptor biologic approved in intravenous (IV) and subcutaneous formulations for treatment of adult patients with moderate to severe active RA. ACTEMRA/RoACTEMRA can be used alone or with MTX in adults who are intolerant to, or have failed to respond to other anti-rheumatic medications.12 In the most recent update to the EULAR RA management guidelines, ACTEMRA/RoACTEMRA is highlighted as the only biologic that has been repeatedly demonstrated to be superior as a monotherapy over MTX or other conventional disease-modifying anti-rheumatic drugs (DMARDs)17.

The ACTEMRA/RoACTEMRA IV formulation is approved in most major countries for polyarticular juvenile idiopathic arthritis (pJIA) or systemic juvenile idiopathic arthritis (sJIA) in children two years of age and older.12 In Europe, ACTEMRA/RoACTEMRA is also approved for use in patients with severe, active and progressive RA (early RA) who previously have not been treated with MTX.12

ACTEMRA/RoACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody, the result of a research collaboration with Roche subsidiary Chugai Pharmaceutical Co., Ltd., An extensive clinical development program of five Phase III trials was designed to evaluate clinical findings of ACTEMRA/RoACTEMRA, all of which met their primary endpoints, and the drug has been approved in Japan since April 2005 as a therapy for Castleman’s disease, and is approved in more than 100 countries worldwide including India, Brazil, Switzerland, and Australia. In April 2008, additional indications for rheumatoid arthritis (RA), polyarticular juvenile idiopathic arthritis and systemic-onset juvenile idiopathic arthritis were also approved in Japan. ACTEMRA/RoACTEMRA was approved in the European Union in January 2009 for the treatment of RA in patients who have either responded inadequately to, or who were intolerant to, previous therapy with one or more disease modifying anti-rheumatic drugs (DMARDs) or tumour necrosis factor (TNF) inhibitors. ACTEMRA/RoACTEMRA was) approved in the United States in January 2010 for treatment of adult patients with moderately to severely active RA who have had an inadequate response to one or more TNF inhibitors.

Roche says the overall safety profile of ACTEMRA/RoACTEMRA is consistent across all global clinical studies. Serious adverse events reported in ACTEMRA/RoACTEMRA clinical studies include serious infections, gastrointestinal perforations and hypersensitivity reactions including anaphylaxis. The most common adverse events reported in clinical studies were upper respiratory tract infection, nasopharyngitis, headache, hypertension and increased ALT. Increases in liver enzymes (ALT and AST) were seen in some patients; these increases were generally mild and reversible, with no evidence of hepatic injuries or any observed impact on liver function. Laboratory changes, including increases in lipids (total cholesterol, LDL, HDL, triglycerides) and decreases in neutrophils and platelets, were seen in some patients without association with clinical outcomes. Treatments that suppress the immune system, such as ACTEMRA/RoACTEMRA, may increase risk of malignancies.

The Roche Group’s immunology medicines include rheumatoid arthritis treatments MabThera/Rituxan (rituximab) and ACTEMRA/RoACTEMRA (tocilizumab), XOLAIR (omalizumab) in asthma, Pulmozyme (dornase alfa) for cystic fibrosis and Esbriet (pirfenidone) for idiopathic pulmonary fibrosis. In addition, MabThera is approved for the treatment of certain types of small-vessel vasculitis. Roches late-stage pipeline includes etrolizumab, which is being studied in ulcerative colitis, and lebrikizumab for severe asthma.

Roche is the world’s largest biotech company, with a range of differentiated medicines for treating cancer, immune disorders, infectious diseases, ophthalmological disorders and neurological diseases. Founded in 1896, Roche has been contributing to global health for nearly 120 years. Twenty-four medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and chemotherapy. In 2014, the Roche Group employed 88,500 people worldwide, invested 8.9 billion Swiss francs in R&D and posted sales of 47.5 billion Swiss francs. Genentech, in the United States, is a wholly owned member of the Roche Group, which is also majority shareholder in Chugai Pharmaceutical, Japan. For more information, visit:

Notes and References:

1. Bijlsma JWJ, et al. Rapid and sustained remission in early rheumatoid arthritis treated to target with tocilizumab, methotrexate, or their combination: the U-ACT-EARLY strategy study. Oral presentation at EULAR, 2015. Abstract number: OP0033. Presented Thursday, 11 June, 2015.

2. De Benedetti F, et al. Safety and Efficacy of Tocilizumab in Patients With Systemic Juvenile Idiopathic Arthritis: 5-Year Data From TENDER, a Phase 3 Clinical Trial. Poster presentation at EULAR, 2015. Poster number: THU0508. Presented Thursday, 11 June, 2015.

3. Khanna D, Denton CP. Evidence-based management of rapidly progressing systemic sclerosis. Best Pract Res Clin Rheumatol 2010; 24: 387400.

4. Krause L, et al. Nutritional status as marker for disease activity and severity predicting mortality in patients with systemic sclerosis. Ann Rheum Dis. 2010;69:19511957.

5. Khanna D, et al. Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis: week 48 data from the faSScinate trial. Oral presentation at EULAR, 2015. Abstract number: OP0054. Presented Thursday, 11 June, 2015.

6. Smolen J, et al. Long-term efficacy of tocilizumab in rheumatoid arthritis for up to 3.5 years. Presentation at ACR, 2009. Abstract number: 413 Presented Sunday, 18 October 2009.

7. Strand V, et al. Improvements in health-related quality of life after treatment with tocilizumab in patients with rheumatoid arthritis refractory to tumour necrosis factor inhibitors: results from the 24-week randomized controlled RADIATE study. Rheum (Oxford) 2012;51(10):18601869.

8. Burmester G, et al. Tocilizumab (TCZ) in combination and monotherapy versus methotrexate (MTX) in MTX-nave patients (pts) with early rheumatoid arthritis (RA): Clinical and radiographic outcomes from a randomized, placebo-controlled trial. Oral presentation at ACR 2013. Abstract number: 2767. Session title: Rheumatoid Arthritis Treatment – Small Molecules, Biologics and Gene Therapy: Efficacy of Approved Biologics. Presented Tuesday, October 29, 2013.

9. Yilmaz S, et al. Early intervention in the treatment of rheumatoid arthritis: focus on tocilizumab. Ther Clin Risk Management 2013;9:403408.

10. Woo P. Systemic juvenile idiopathic arthritis: diagnosis, management, and outcome. Nat Clin Pract Rheumatol 2006; 2: 2834.

11. De Benedetti F. Inflammatory cytokines in the pathogenesis and treatment of systemic juvenile idiopathic arthritis Basic science for the clinician. Pediatric Rheumatology Online Journal 2005. Vol 3:2.
12. RoACTEMRA Summary of Product Characteristics. Available at:

13. Hajj-ali R. Merck Manuals. Systemic Sclerosis. Available at:

14. University of Michigan Health System, Scleroderma Program, Division of Rheumatology. What is Scleroderma? Available at:

15. Clements PJ, et al. Skin thickness score as a predictor and correlate of outcome in systemic sclerosis. Arth and Rheum. 2000; 43(11): 2445-2454.

16. Steen VD, Medsger Jr TA. Improvement in skin thickening in systemic sclerosis associated with improved survival. Arth and Rheum. 2001; 44(12): 2828-2835.

17. Smolen JS et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2014;73:492509.

European League Against Rheumatism

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