This document posted Recommendations and Reasons April 2011 Committee to Evaluate Drugs (CED) Golimumab for ankylosing spondylitis Product: Highlights of Recommendation: Background: GOLIMUMAB (Simponi®) ♦ Golimumab belongs to a class of drugs Ankylosing spondylitis is a chronic, Class of drugs: called tumor necrosis factor (TNF) inflammatory disease that mainly biologic response modifiers; tumor inhibitors. It is licensed for use in affects the joints between the spinal necrosis factor (TNF) alpha inhibitors several different indications. This bones and the joints between the review considered the use of spine and the pelvis. Early symptoms Indication: golimumab for the treatment of include back pain and stiffness. Over ankylosing spondylitis. time, ankylosing spondylitis causes ankylosing spondylitis ♦ Clinical study evidence supports that the affected spinal bones to fuse golimumab improves the symptoms of together, causing significant pain Manufacturer: and limiting movement. The disease Schering Plough Inc. ankylosing spondylitis, such as physical function and pain. Golimumab has also can also cause inflammation in other been shown to improve a patient’s joints away from the spine and in quality of life. other organs (e.g. the eyes, heart, lungs, and kidneys). CED Recommendation ♦ Two different doses of golimumab, 50mg and 100mg every four weeks, There is no known cure for The CED recommended that were evaluated. The higher 100mg ankylosing spondylitis. The disease is dose was not shown to be significantly golimumab (Simponi®) not be managed with physical therapy, more effective than the 50mg dose. funded, on the basis that this medications and surgery. No drug drug has not been shown to ♦ There are no direct comparison studies therapy has been shown to alter the provide added clinical benefits evaluating the efficacy and safety of progression of this disease.The compared with available golimumab versus other TNF primary drug treatment consists of treatment alternatives and it is inhibitors. The Ontario Public Drug non-steroidal anti-inflammatory uncertain whether it offers an Programs currently fund three other drugs (NSAIDs), which help to economic advantage. TNF inhibitors for ankylosing reduce pain, swelling and stiffness. spondylitis. There is no evidence that In some patients, the addition of golimumab is therapeutically superior corticosteroids and disease modifying to these alternatives. anti-rheumatic drugs (DMARDs) may ♦ Golimumab costs approximately also be considered. Biologic $17,300 per patient per year when response modifiers are a newer class administered at the Health Canada of drugs that can be used to treat Executive Officer Decision recommended dose of 50mg once a ankylosing spondylitis and are month. At this dosing regimen, it may thought to work by blocking a Taking into consideration the CED’s provide some cost savings relative to protein involved in inflammation. recommendation and based on a comparator products. However, the cost agreement with the cost advantage is small and would not Golimumab (Simponi®) is a biologic manufacturer, the Executive be realized if the drug was agent that belongs to a subclass of Officer decided to fund golimumab administered every four weeks (the drugs called tumor necrosis factor (Simponi®) for the treatment of dosing schedule used in the key clinical (TNF) alpha inhibitor. Golimumab is indicated for reducing the signs and ankylosing spondylitis through the study). ♦ Overall, the Committee noted that symptoms of ankylosing spondylitis Exceptional Access Program in adults who have had an according to specific criteria. while golimumab is efficacious in improving the symptoms of inadequate response to conventional ankylosing spondylitis, other TNF therapies. Status inhibitors are already funded for this indication. Golimumab has Funded through the Exceptional not demonstrated clinical Access Program. superiority to comparator products and the suggested cost savings may not be realized. continued... Detailed Discussion: EAP Funding: ♦ A single randomized controlled trial ♦ Direct head-to-head studies Taking into consideration the CED’s was identified for this review. This is comparing golimumab to other TNF recommendation and based on a cost a 24-week study comparing the inhibitors have not been conducted. agreement with the manufacturer, efficacy of golimumab to placebo in There is no evidence that the Executive Officer decided to fund 356 patients with active ankylosing golimumab offers any therapeutic golimumab (Simponi®) for the spondylitis despite having received advantage compared to available treatment of ankylosing spondylitis maximal doses of NSAIDs or could alternatives. through the Exceptional Access not use NSAIDs due to intolerance ♦ Similar to other treatments for Program (EAP). or contraindications. ankylosing spondylitis, golimumab has ♦ At week 14 of the study, 59% of not been shown in clinical studies to The EAP reimbursement criteria can patients receiving golimumab 50mg slow disease progression. be found at: http://www.health.gov.on.ca/english/ every four weeks, compared with ♦ If administered at the Health Canada providers/program/drugs/pdf/ 22% of patients receiving placebo, recommended dose of 50mg monthly frequently_requested_drugs.pdf experienced at least 20% (i.e. 12 doses per year), golimumab improvement in their signs and costs slightly less than other TNF symptoms, as measured by the inhibitors. However, if golimumab was Ankylosing Spondylitis Assessment given at 50mg every four weeks (the (ASAS) criteria. (The ASAS criteria dosing regimen used in the clinical take into consideration physical trial), its treatment cost would be function, inflammation, patient’s similar to that of alternative TNF assessment of the disease, and inhibitors. back pain.) Patients who were ♦ Overall, the CED noted that while treated with golimumab also golimumab has been shown to experienced greater improvements improve the symptoms of in various other measures of ankylosing spondylitis, this drug disease activity and in their quality has not been proven to provide of life. therapeutic superiority or clear ♦ The study reported no significant value for money relative to difference between patients treated existing treatment options. with golimumab and those on placebo with respect to time lost from work and spinal mobility. ♦ Two dosing regimens of golimumab were evaluated in the study. Efficacy appeared similar between patients who received golimumab 50mg and those who received 100mg every four weeks. ♦ No significant differences were noted in the clinical trial between golimumab and placebo with respect to serious adverse events, infections, cancer, and withdrawals Ministry of due to adverse events. However, the trial duration was short. Given Health and Long-Term Care that ankylosing spondylitis is a Ontario Public Drug Programs chronic condition and long-term therapy would be required, the For more information, please contact: ability to generalize these safety Ministry of Health and Long-Term Care results is limited. Ontario Public Drug Programs ♦ Patients who had previously tried Hepburn Block, 9th Floor other TNF inhibitors or those with complete ankylosis of the spine 80 Grosvenor Street, Queen’s Park were excluded from the clinical Toronto, Ontario M7A 1R3 study. As such, the efficacy of or click: (http://www.health.gov.on.ca/ golimumab in these patient english/providers/program/drugs/ populations is unknown. ced_rec_table.html)