Ozoralizumab reduces RA signs, symptoms in patients who fail methotrexate
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Ozoralizumab, in either the 30 mg or 80 mg formulation, significantly reduces rheumatoid arthritis signs and symptoms in patients with an inadequate response to methotrexate, according to data published in Arthritis & Rheumatology.
“Despite the advances in management, an unmet therapeutic need in RA still remains, as current therapeutic agents sometimes achieve only partial response and only 20% to 25% of patients achieve complete remission,” Tsutomu Takeuchi, MD, PhD, of the Keio University School of Medicine, in Tokyo, and co-authors wrote. “Ozoralizumab is a next-generation anti-TNF antibody. It is a 38 kDa trivalent Nanobody compound consisting of the two humanized anti-human TNF VHH antibodies and one humanized anti-human serum albumin (HSA) VHH antibody.
“VHH antibodies are derived from a special type of heavy chain-only antibody produced naturally by llamas and other camelid species,” they added. “Ozoralizumab has an inhibitory activity against human TNF and a specific binding ability to HSA, which lead to potent neutralization of the action of TNF, and prolonged serum half-life by interacting with serum albumin.”
To investigate the impact of subcutaneous ozoralizumab (Ablynx NV) 30 mg or 80 mg in patients with RA who had an inadequate response to methotrexate alone, Takeuchi and colleagues designed a multicenter, randomized, placebo-controlled, double-blind, parallel-group confirmatory trial with a 24-week double-blind treatment period. The first treatment period was followed by a 28-week open-label treatment period.
Throughout the first period, patients were randomized in a 2:2:1 ratio to receive ozoralizumab 30 mg, ozoralizumab 80 mg or placebo, respectively. Therapy was given subcutaneously every 4 weeks with methotrexate, the authors wrote. At 16 weeks, patients who met early escape criteria were shifted from placebo to ozoralizumab 30 mg, and from ozoralizumab 30 mg to 80 mg, under double-blind conditions.
To be eligible for the trial, patients with an inadequate response to methotrexate were required to be aged 20 to 75 years and fulfill the 2010 RA classification criteria from the American College of Rheumatology. Patients were excluded if there were abnormal findings on a chest X-ray indicating a malignant tumor, interstitial pneumonia or other infections. Patients with active tuberculosis were also excluded.
The primary outcome was the ACR20 response rate at 16 weeks and the change in baseline in the modified total Sharpe score at 24 weeks. Secondary efficacy endpoints included ACR50 and ACR70 responses, DAS28, patient’s global assessment of disease activity with a visual scale, patient’s pain assessment using a visual scale, simplified disease activity index scores, Boolean remission, health assessment questionnaire disability index, erosion score and JSN score, the authors wrote.
In all, 395 patients were randomized. In both groups receiving ozoralizumab, ACR20 response at week 16 was significantly higher than those in the placebo group (P < .001). Among the patients receiving ozoralizumab 30 mg, 79.6% achieved ACR20, compared with 75.3% in the 80 mg group and 37.3% in the placebo group. Serious adverse events were observed in four patients in the 30 mg group, and in five patients who received 80 mg. One of the serious adverse reactions in the 80 mg group, disseminated tuberculosis, resulted in the death of a patient.
“This phase II/III trial in patients with RA who showed inadequate response to MTX demonstrated that both 30 mg and 80 mg ozoralizumab groups achieved statistically significant improvements in ACR20, which was one of the primary endpoints, compared with the placebo group,” Takeuchi and colleagues. “The incidences of AE in the ozoralizumab 30 mg and 80 mg groups were comparable. AEs observed during administration of ozoralizumab were comparable to that of other TNF inhibitors approved by regulators, in terms of frequency and type.”
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