Staff Writer

Roche subsidiary Genentech Inc. and Biogen Idec Inc. said their first Phase III trial with anti-CD20 antibody ocrelizumab achieved its primary endpoint of improving ACR20 scores in rheumatoid arthritis patients.

The STAGE trial included 1,015 RA patients who had not adequately responded to methotrexate. Patients were randomized to receive background methotrexate plus either placebo or one of two ocrelizumab doses. The companies said ocrelizumab significantly improved ACR20 scores, which reflect a 20 percent improvement in joint swelling or tenderness, at both 24 and 48 weeks.

South San Francisco-based Genentech and Cambridge, Mass-based Biogen said additional details will be presented at a medical meeting, but the firms did call out a bit of safety data in their press release. They said that while overall adverse events were comparable between the ocrelizumab and placebo groups, there was a higher percentage of serious infections in the pooled ocrelizumab group.

Infections have proven to be a bugaboo for ocrelizumab. In October, concern over opportunistic infection rates, which were particularly high in Asia, prompted Genentech and Biogen to halt dosing of STAGE patients in that region. Dosing in Asia of two additional Phase III ocrelizumab rheumatoid arthritis trials - SCRIPT and FEATURE - also was halted, although all three trials continued to dose patients in the rest of the world.

Additionally, a fourth Phase III ocrelizumab rheumatoid arthritis trial, dubbed FILM, was put on clinical hold by the FDA due to opportunistic infection concerns. A Phase III trial of ocrelizumab in lupus nephritis, called BELONG, also was halted.

Genentech and Biogen have thus far declined to specify what kinds of opportunistic infections were observed or to provide additional details, as data analysis is ongoing.

The halted FILM study was focused on methotrexate-naïve RA patients, while the newly reported STAGE study was in methotrexate-inadequate responders. Data from SCRIPT, in inadequate responders to tumor necrosis factor-alpha inhibitor therapy, and FEATURE, which looks at a single infusion rather than the standard double infusion of ocrelizumab, are expected in the first half of 2010, as are the available data from FILM.

Shares of Biogen (NASDAQ:BIIB) rose a modest 39 cents to close at $48.65 on Friday. Investors appeared to be reserving their excitement until additional data show if and where ocrelizumab might fit into the crowded RA treatment cycle.

Rituxan (rituximab) from Genentech and Biogen already has approval for rheumatoid arthritis patients who have failed anti-TNF-alpha therapy. Like ocrelizumab, Rituxan targets CD20. But while Rituxan is a chimeric antibody, ocrelizumab is fully humanized, which theoretically means it should have fewer immunogenicity issues - although that hasn't been proven thus far.

Copenhagen, Denmark-based Genmab A/S also is looking to move its fully human anti-CD20 antibody, Arzerra (ofatumumab), into the RA space. Arzerra gained FDA approval for chronic lymphocytic leukemia this fall, and Phase III RA trials are under way. (See BioWorld Today, Oct. 28, 2009.)

But while the first of Arzerra's Phase III RA trials met its ACR20 improvement endpoint, analysts were not particularly optimistic about the data. Arzerra improved ACR20 scores 23 percent over placebo (p < 0.001), which the experts said was about on par with Rituxan but less effective than the 30 percent to 40 percent improvement seen with anti-TNF-alpha drugs. (See BioWorld Today, July 31, 2009.)

Analysts predict that like Rituxan, Arzerra may find a home with patients who fail anti-TNF-alpha therapy. Genmab also is developing a subcutaneous formulation to differentiate Arzerra from intravenous Rituxan and ocrelizumab. That's the same strategy being tried by Immunomedics Inc. and Nycomed GmbH with their subcutaneous humanized anti-CD20 antibody, veltuzumab.

Genmab CEO Lisa Drakeman told BioWorld Today last summer that Rituxan makes about $750 million a year in the anti-TNF-alpha failure market. But as Arzerra, ocrelizumab, veltuzumab and other would-be competitors close in, the hope is that some of the products will be good enough, both on the safety and the efficacy fronts, to gain approvals for earlier-stage RA patients.

Ocrelizumab also recently completed a Phase II trial in relapsing-remitting multiple sclerosis. Genentech spokeswoman Erica Jefferson said the trial met its endpoint.

Behind ocrelizumab, Genentech and Biogen are partnered on the humanized anti-CD20 antibody GA101, which is in Phase II for hematologic cancers. Roche acquired the drug through its buyout of GlycArt AG in 2005.

Development of Genentech and Biogen's anti-CD20 antibodies must be cleared by a joint committee of representatives from both companies, according to an arbitration ruling this summer. The two companies had gotten into a spat as Biogen attempted to rein in new development that might lower its royalties. (See BioWorld Today, June 18, 2009.)

Published  December 14, 2009