An Endpoint Used in Clinical Trials of Most of the Blockbuster Drugs for Rheumatoid Arthritis

Thursday 8 March 2012, Amsterdam

The report examines different aspects of clinical trial endpoints in autoimmune disorders, such as analysis of major marketed autoimmune drugs with an emphasis on safety and efficacy details, Phase II and Phase III clinical trial analysis for both completed and ongoing clinical trials, most promising autoimmune drugs, and terminated trial analysis. The company profiles highlight the autoimmune drugs of different companies.

ACR Response Criteria - An Endpoint Used in Clinical Trials of Most of the Blockbuster Drugs for Rheumatoid Arthritis

Major marketed drugs for RA are Enbrel (etanercept), Humira (adalimumab), Remicade (infliximab), Rituxan (rituximab), and Celebrex (celecoxib). With a sales figure of more than one billion, all five drugs are considered to be blockbusters. The endpoints used in their clinical trials are American College of Rheumatology (ACR) criteria. ACR response criteria consist of clinical symptoms and signs of inflammation including fatigue, joint pain, morning stiffness, joint tenderness, joint swelling, and Erythrocyte Sedimentation Rate (ESR). This is a used as a major endpoint in most of the clinical trials for RA.

Most Widely Used Secondary Endpoints in the Clinical Trials for Top Five Autoimmune Disorders

From 2000 to 2010, the ACR response criteria was the most commonly used secondary endpoint in clinical trials for RA, followed by clinical remission which is most widely used in clinical trials for ulcerative colitis. Psoriasis Area Disease Severity (PASI) Score, Expanded Disability Status Scale (EDSS) and Crohn’s Disease Activity Index (CDAI) are the secondary endpoints which are most widely used in clinical trials for psoriasis, MS and CD respectively.

Safety and Efficacy Issues and Failure to Meet Primary and Secondary Endpoints Led to Discontinuation of Most Drugs

Antova was developed by Biogen Idec for the treatment of MS and many other diseases. Biogen Idec stopped all clinical trials as some patients experienced signs of blood clots. The company announced that it had halted six of its Phase II clinical trials due to safety issues.

Orencia (abatacept, CTLA4-Ig, BMS-188667), a drug for the treatment of UC developed by Bristol- Myers Squibb, was discontinued. The study was terminated due to a lack of efficacy in the first group of subjects in the induction period.

Raptiva (efalizumab) is a drug designed by Genentech and Merck Serono to treat psoriasis. It was approved in 2003 in the US and prescribed for adults with moderate to severe chronic psoriasis. In October 2008, the US Food and Drug Administration (FDA) passed a rule that the drug must carry stricter warnings about the risk of Progressive Multifocal Leukoencephalopathy (PML), a brain disorder caused by reactivation of latent John Cunningham (JC) virus infection due to its action of suppressing the immune system. On March 13, 2009, the FDA approved safety labeling revisions for Raptiva regarding the risks associated with the drug, leading to its withdrawal from the market as of June 8, 2009. The European Medicines Agency (EMEA) recommended the withdrawal of the drug from the European Union (EU) in February 2009 as its associated risks outweighed its efficacy.