Whether this slight imbalance in baseline characteristics or the manner in which atacicept targets B cells had any effect on the study’s outcomes remains to be seen, Dr. Kappos said.
In the other phase II trial, 220 patients with relapsing remitting MS who were randomized to receive two cycles of ocrelizumab for a total infusion dose of 600 mg or 2,000 mg, given in two divided doses of 300 mg or 1,000 mg, respectively, separated by 14 days. Other patients were given matching placebo infusions or open-label (rater-blinded) intramuscular interferon beta-1a (IFNB-1a, Avonex) 30 mcg once weekly.
Ocrelizumab not only significantly reduced the ARR by 73%-80%, but also reduced the mean number of GdE T1 lesions by 86%-96% versus placebo (P less than .0001). The ARRs for ocrelizumab at 24 weeks were significantly reduced with 600 mg and 2,000 mg ocrelizumab, compared with placebo, and, in an exploratory analysis, with IFNB-1a. The ARRs were 0.13 for the 600-mg dose and 0.17 for the 2,000-mg dose, compared with 0.64 for placebo and 0.36 for IFNB-1a, reported Dr. Kappos, who also was lead author on this study (Lancet 2011 Nov. 1 [doi:10.1016/S0140-6736(11)61649-8]).
"This doesn’t mean that we won’t have B-cell specific treatments for MS; however, we have more work to do in this area."
The mean total number of GdE T1 lesions over weeks 12, 16, 20, and 24 was 0.8 for both 600 mg and 2,000 mg ocrelizumab, which was significantly different from the mean of 6.6 lesions observed in the placebo group.
The study shows "the effectiveness of B cell depletion with both ocrelizumab doses ... with favorable short-term safety profile," according to the study authors. Dr. Kappos also recently presented long-term data from the trial in a poster at the congress.
After week 24, all 183 patients who continued to participate in the 96-week extension study were treated open-label with either 600 mg or 2,000 mg ocrelizumab.
At week 96, the mean ARR was 0.18 for patients who received open-label ocrelizumab 600 mg and 0.22 for those who received 2,000 mg. Overall, 67.3% of patients who took the 600-mg dose and 76.4% of patients who took the 2,000-mg dose were free of any clinical disease activity (no relapses or progression on the Expanded Disability Status Scale). In addition, 78.2% and 80.0% of patients, respectively, remained relapse-free. There were no GdE T1 lesions observed.
Exploratory analyses showed that patients who had switched to using ocrelizumab after placebo or IFNB-1a experienced benefits similar to those in patients who had remained on ocrelizumab therapy.
ATAMS was supported by Merck Serono and EMD Serono. The ocrelizumab trial was supported by F. Hoffman-La Roche. and Biogen Idec. Dr. Kappos and many of his coauthors have received institutional research support from those companies and other pharmaceutical developers of MS therapies. Dr. Gold disclosed receiving honoraria and research support from Bayer HealthCare, Biogen Idec, Merck Serono, and Novartis. Dr. Coetzee had no disclosures.