Roche and Biogen Idec's ocrelizumab looks positive in Phase II for RRMS
This article was originally published in Scrip
Roche and Biogen Idec's humanised anti-CD20 monoclonal antibody ocrelizumab has achieved positive results in a 220-patient Phase II study for the treatment of relapsing-remitting multiple sclerosis (RRMS), top-line data show.
Roche said that ocrelizumab produced a highly statistically significant reduction in the signs of disease activity as measured by brain lesions versus placebo, the primary endpoint, compared with placebo. Further data will be presented in an upcoming scientific meeting. Details of when ocrelizumab will move into Phase III will be announced following a full review of the Phase II data.
Ocrelizumab is an investigational humanised version of the companies' chimaeric antibody rituximab (Rituxan/MabThera), which is approved to treat non-Hodgkin's lymphoma, B-cell lymphoma, rheumatoid arthritis and chronic lymphocytic leukaemia. Rituximab– which selectively targets and depletes CD20+ B lymphocytes – is also in Phase II trials for RRMS. Ocrelizumab is also in Phase III development for rheumatoid arthritis and lupus nephritis.
Being fully humanised, ocrelizumab is designed to avoid some of the side-effects caused by monoclonal antibodies yielded from mice, which are regarded as foreign by the human immune system and can cause systemic inflammatory effects.
The 24-week randomised, partially-blinded Phase II study compared two intravenous doses of ocrelizumab (600mg and 2g) with placebo and interferon beta-1a (Biogen Idec's Avonex) controls, given in four treatment cycles in both treatment-naïve and previously treated patients.
Patients were assessed every four weeks by measuring brain lesions via MRI scans. The primary endpoint was efficacy measured by gadolinium-enhancing T1 lesions observed in MRI scans of the brain at weeks 12, 16, 20 and 24 compared with placebo.
The secondary endpoints included annualised relapse rate at week 24, total new gadolinium-enhancing T1 lesions at four-weekly intervals, tolerability and overall safety of the drug. Safety and tolerability data continue to be collected.
rights
Both rituximab and ocrelizumab are being developed under an agreement for anti-CD20 molecules between the companies, but the decision-making rights for certain of these molecules, including ocrelizumab, have in the past been subject to some tension. However, an arbitration panel ruling in June regarding the disagreements reaffirmed Biogen Idec's contractual right to participate fully in strategic decisions regarding the development of rituximab and other anti-CD20 antibodies subject to the collaboration with Genentech.
Other candidates for RRMS include the first two potential oral therapies: Novartis's oral 1-sphingosine phosphate receptor modulator fingolimod, which is expected to be filed at the end of the year; and Merck Serono's oral synthetic purine analogue Cladribine Tablets, which has been filed in the EU, but for which the US FDA refused to file the NDA in its current format (scripnews.com, December 1st, 2009).