Date: 2014-03-04
Type of information: Results
phase: 2
Announcement: results
Company: Xoma (USA - CA)
Product: gevokizumab
Action
mechanism: monoclonal antibody. Gevokizumab (XOMA 052) is a potent monoclonal antibody with unique allosteric modulating properties and the potential to treat patients with a wide variety of inflammatory diseases and other diseases. Gevokizumab binds strongly to interleukin-1 beta (IL-1 beta), a pro-inflammatory cytokine that has been shown to be involved in Behçet\'s and other forms of non-infectious uveitis, cardiovascular disease, and other auto-inflammatory diseases. In binding to IL-1 beta, gevokizumab inhibits the activation of the IL-1 receptor, thereby modulating the cellular signaling events that produce inflammation.
Gevokizumab currently is being studied in a global Phase 3 clinical program, termed EYEGUARD™, which is being conducted by Servier and Xoma. This program is designed to determine gevokizumab\'s ability to treat acute non-infectious uveitis (NIU) in EYEGUARD-A, to prevent disease flares in patients with Behçet\'s uveitis in EYEGUARD-B, and to prevent disease flares in NIU patients who are controlled with steroids and immunosuppressants in EYEGUARD-C.
Disease: erosive osteoarthritis of the hand (EOA)
Therapeutic area: Inflammatory diseases - Rheumatic diseases
Country:
Trial
details: Xoma conducted two separate double-blind, placebo-controlled clinical studies in patients with EOA. The first study (Study 160) enrolled 85 patients who were diagnosed with EOA and who had a high-sensitivity C-reactive protein (CRP) level ?2.5 mg/L. CRP is recognized as a biomarker for generalized inflammation. The second study (Study 162) enrolled 92 patients who met the criteria for the first study but did not have elevated CRP. In both studies, patients were randomized 2:1 to receive either gevokizumab 60mg or placebo, dosed subcutaneously once monthly. Both studies were designed to determine if gevokizumab could improve the pain, stiffness, and physical function associated with EOA, based upon the Australian/Canadian Osteoarthritis Hand Index (AUSCAN™) scoring scale. AUSCAN is a validated self-administered questionnaire specifically designed to assess the three dimensions of pain, disability, and joint stiffness of osteoarthritis of the hand using a series of 15 questions. Study 160 assessed the change in AUSCAN score from baseline at Days 84 and 168 in addition to assessing improvements of the effected joints from baseline using radiographic and MRI images taken at Days 84 and 168. Study 162 assessed the change in AUSCAN score from baseline at Day 84, the results in the second study did not show the same strength as the Day 84 results from Study 160.
Latest
news: * On March 4, 2014, Xoma Corporation has provided an update on its gevokizumab development program. Based on results from the Company's Phase 2 program in patients with erosive osteoarthritis of the hand (EOA), Xoma does not intend to launch pivotal development for the broad EOA indication. The Company will conduct a review of the full dataset to determine if there is a segment of the patient population that best responds to gevokizumab therapy prior to initiating any potential additional clinical studies in this indication. Gevokizumab appeared to be well tolerated, and the most common adverse events were comparable between both the gevokizumab and placebo groups. Xoma will continue to focus its efforts on completing the EYEGUARD™ Phase 3 clinical program, preparing to initiate its Phase 3 program in patients with pyoderma gangrenosum, and assessing gevokizumab in pilot studies of other rare diseases that are in need of new therapeutic options.
Xoma conducted two separate double-blind, placebo-controlled clinical studies in patients with EOA. The first study (Study 160) enrolled 85 patients who were diagnosed with EOA and who had a high-sensitivity C-reactive protein (CRP) level ?2.5 mg/L. The second study (Study 162) enrolled 92 patients who met the criteria for the first study but did not have elevated CRP. In both studies, patients were randomized 2:1 to receive either gevokizumab 60mg or placebo, dosed subcutaneously once monthly. Both studies were designed to determine if gevokizumab could improve the pain, stiffness, and physical function associated with EOA, based upon the Australian/Canadian Osteoarthritis Hand Index (AUSCAN™) scoring scale. The initial results from Study 160 showed separation between the gevokizumab and placebo scores favoring gevokizumab over the 84-day period. While the gevokizumab-treated patients continued to show an improvement in all AUSCAN measures over their baseline scores after 168 days of therapy, the placebo treated patients showed a greater improvement over the final three months of the study, eliminating the separation seen between placebo and actively treated patients by the Day 168 time point. The Company's primary analyses and other objective measures, such as MRIs and radiographs, did not suggest a significant drug-related benefit after six months.
Xoma has begun analyses of relevant patient subgroups, and these data have shown placebo response was driven by patients with milder disease at baseline. Comparisons of patients with more severe pain (visual analog scale ? 75/100) at baseline show a consistent trend favoring gevokizumab in all components of their AUSCAN scores. In both proof-of-concept studies, gevokizumab demonstrated a statistically significant effect on CRP levels over the full study periods. It is possible these observations, as well as further analyses, could provide a reasonable group to study in future trials but it is too early to tell at this point.
Gevokizumab was generally well tolerated, and there were no drug-related serious adverse events reported in these studies. The most common adverse events were headache, pain, arthralgia, urinary tract infections, upper respiratory tract infections and pneumonia, and they were comparable between gevokizumab and placebo.
"We have rapidly advanced our pyoderma gangrenosum clinical program since we launched our pilot study in June of 2013, and our End of Phase 2 meeting with the Food and Drug Administration will be taking place in March. We expect we will be able to announce our Phase 3 clinical program in this rare and serious indication during April," commented Paul Rubin, MD, Senior Vice President Research and Development and Chief Medical Officer of Xoma.
* On July 22, 2013, Xoma has announced that it has completed patient enrollment in the Phase 2 proof-of-concept (POC) study designed to evaluate the potential for gevokizumab to improve pain symptoms, physical function and structural abnormalities in patients with active inflammatory, erosive osteoarthritis of the hand (EOA) and elevated C-reactive protein (CRP) levels. Xoma\'s study enrolled approximately 90 patients who were randomized 2:1 to receive 60mg of gevokizumab dosed subcutaneously once monthly or placebo. Xoma anticipates having preliminary top-line data for the AUSCAN score in October.
Xoma has a Proof-of-Concept (POC) program underway in which the Company is exploring the efficacy and safety of gevokizumab in multiple indications. Xoma anticipates selecting its next Phase 3 indication by the end of 2013. Xoma anticipates full results from its two POC studies in patients with erosive osteoarthritis of the hand and data from the National Eye Institute\'s study of gevokizumab in patients with active non-infectious anterior scleritis later this year. Additionally, the Company recently launched a pilot study in pyoderma gangrenosum, a rare skin ulceration disease. Separately, Servier initiated a Phase 2 study to determine gevokizumab's ability to reduce arterial wall inflammation in patients with marked atherosclerotic plaque inflammationand who have experienced an acute coronary syndrome in the previous twelve months, as well as a POC study in polymyositis/dermatomyositis.
