Biosimilars are developed as an equivalent to biologic agents that are already in use, but have an expired patent protection. Biosimilars also require extensive testing to ensure safety and therapeutic effectiveness. Biosimilars for rheumatoid arthritis are currently under investigation.
A biologic medicine is an agent that is designed and manufactured in a living system (e.g. plant or animal cells), that are produced using recombinant DNA technology. They usually consist of large, complex molecules, or a mixture of molecules, as opposed to a drug which is usually developed via chemical synthesis. A biosimilar is a medicine that is similar to a biologic agent. Biosimilars are independently developed once the patent protection has expired on a biologic agent.
Biologics specifically inhibit immune system components and prevent inflammation; therefore, the use of biologic agents has greatly improved the treatment of rheumatoid arthritis. The use of biologics for rheumatoid arthritis has resulted in a reduction of radiologic progression when compared to conventional antirheumatic drugs. While biologics have proved superior for the treatment of rheumatoid arthritis, barriers still remain for patients who would benefit from treatment, primarily affordability.
While biologic agents are costly, the development of biosimilars would potentially allow more patients to be treated, possibly at an earlier time point during disease progression, where they would be most effective. While the greatest advantage of biosimilar development is the affordability, the developmental process for biosimilars remains stringent, ensuring that biosimilars maintain their therapeutic effect, while not compromising on patient safety. There are three actively recruiting clinical trials currently investigating biosimilars for rheumatoid arthritis.
SB5 as biosimilar to Humira (Adalimumab)
Humira (Adalimumab) is a human monoclonal antibody designed to inhibit the protein TNF. Humira prevents the damaging effects of excess TNF that occurs in rheumatoid arthritis, resulting in a reduction of inflammation. SB5 is a biosimilar to Humira that is currently under development by Samsung Bioepis Co., Ltd. A phase 3 clinical trial assessing the safety, efficacy, and tolerability of SB5 compared with Humira in patients with moderate to severe rheumatoid arthritis is currently underway in Lithuania and Poland. Participants who are 18-75 years of age, who have been diagnosed with rheumatoid arthritis for at least 6 months (but less than 15 years), and who have moderate to severe rheumatoid arthritis despite treatment with methotrexate, will be included in the study.
CHS-0214 as biosimilar to Enbrel (Etanercept)
Enbrel (Etanercept) is a fusion protein that interferes with TNF function. In this way, it also reduces the damaging effects of high levels of TNF in rheumatoid arthritis. Enbrel was the first biologic approved for treatment of moderate to severe arthritis. A 24-week, phase 3 clinical trial of the proposed biosimilar, CHS-0214, is being conducted by Coherus Biosciences, Inc. to determine the safety and efficacy in patients with active rheumatoid arthritis who have not responded to methotrexate treatment, and who have not previously been treated with any biologic agents. Participants included in the study will be older than 18, with a diagnosis of rheumatoid arthritis for more than 6 months. The study is being conducted at the Altoona Center for Clinical Research in Duncansville, Pennsylvania, US.
BCD-020 as biosimilar to MabThera (Ritixumab)
MabThera (Ritixumab) is a monoclonal antibody against the CD20 protein present on the B cells of the immune system. The proposed biosimilar to MabThera; BCD-020, is under development by Biocad. A phase 3 safety and efficacy study of BCD-020 in combination with methotrexate, compared to MabThera with methotrexate is underway at 56 locations in Belarus, Colombia, India, Russian Federation, and Ukraine. Patients who are 18-80 years of age who have been diagnosed with rheumatoid arthritis, and have had active disease within the past 3 months will be included in the study.
Dae Hyun Yoo “The rise of biosimilars: potential benefits and drawbacks in rheumatoid arthritis.” Expert Review of Clinical Immunology, August 2014, Vol. 10, No. 8 , Pages 981-983.
Clinicaltrials.gov “A Study Comparing SB5 to Humira® in Subjects With Moderate to Severe Rheumatoid Arthritis Despite Methotrexate Therapy”Available from: http://www.clinicaltrials.gov/ct2/show/NCT02167139?term=biosimilar&recr=Open&no_unk=Y&rank=8Last Accessed: Dec 3, 2014.
Clinicaltrials.gov “Comparison of CHS-0214 to Enbrel (Etanercept) in Patients With Rheumatoid Arthritis (RA) (CHS-0214-02)”Available from: http://www.clinicaltrials.gov/ct2/show/NCT02115750?term=biosimilar&recr=Open&no_unk=Y&rank=10 Last Accessed: Dec 3, 2014.
Clinicaltrials.gov “Study of Safety and Efficacy of BCD-020 Comparing to MabThera in Patients With Rheumatoid Arthritis (BIORA)”Available from: http://www.clinicaltrials.gov/ct2/show/NCT01759030?term=biosimilar&recr=Open&no_unk=Y&rank=14 Last Accessed: Dec 3, 2014.
Humira Information Sheet, Available from: https://www.humira.com/rheumatoid-arthritis/how-humira-works-for-ra Last Accessed: Dec 3, 2014.
Enbrel Information Sheet, Available from:http://www.enbrel.com/how-ENBREL-works-rheumatoid-conditions.jspx Last Accessed: Dec 3, 2014.
Image courtesy of Serge Bertasius Photography at FreeDigitalPhotos.net
Written by Deborah Tallarigo, PhD