Saw the previous links/articles...i think the one I came across was about the same/similar study, but added the following information:
http://www.medpagetoday.com/Neurology/M ... is/tb/8345
"But despite the favorable results, rituximab's lead commercial sponsor, Genentech, is dropping the drug from further development for relapsing-remitting MS. Instead, the company is focusing on ocrelizumab, a second-generation agent with the same biological target, a spokesperson said."
Rituximab Effective Against MS in Phase II Trial
By John Gever, Staff Writer, MedPage Today
Published: February 13, 2008
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine. Earn CME/CE credit
for reading medical news
SAN FRANCISCO, Feb. 13 -- Two doses of rituximab (Rituxan) diminished relapsing-remitting multiple sclerosis lesions and clinical symptoms for nearly a year, researchers here said.
* Explain to interested patients that the study found that rituximab reduced the number of relapses and the number and volume of lesions over 48 weeks in patients with relapsing-remitting MS.
* Explain that side effects rates were generally similar to placebo except for infusion-related reactions after the first rituximab dose.
* Point out that longer-term efficacy and rare side effects could not be determined in this study.
* Explain that rituximab is not approved for this indication and that the company making it does not plan to seek such approval.
The drug cut in half the number of patients developing relapses, relative to placebo, and reduced gadolinium-enhancing lesion counts to near zero after 48 weeks, reported Stephen L. Hauser, M.D., of the University of California San Francisco, and colleagues in the Feb. 14 issue of the New England Journal of Medicine.
"The results of this phase II trial provide MRI and clinical evidence that selective CD20-positive B-cell depletion is a potentially effective approach in the treatment of relapsing-remitting multiple sclerosis," they wrote.
But despite the favorable results, rituximab's lead commercial sponsor, Genentech, is dropping the drug from further development for relapsing-remitting MS. Instead, the company is focusing on ocrelizumab, a second-generation agent with the same biological target, a spokesperson said.
Dr. Hauser and colleagues reported final data from the double-blind, multicenter Helping to Evaluate Rituxan in Relapsing-Remitting Multiple Sclerosis (HERMES) trial.
It randomized 104 patients 2:1 to rituximab or placebo. The drug was given at 1,000 mg IV on days one and 15.
Patients 18 to 55 with at least one relapse during the preceding year and an entry score of no more than 5.0 on the Expanded Disability Status Scale were included.
Among the exclusion criteria were relapse within the previous 30 days or recent treatment with other biologics, immunosuppressant drugs, or systemic corticosteroids.
The study's primary endpoint was the effect on gadolinium-enhancing lesion counts as seen on MRI brain scans at weeks 12, 16, 20, and 24.
More than 80% of the rituximab group had no lesions at these evaluations, compared 51.4% of the placebo group (P<0.001).
Mean lesion counts across the evaluation points were 5.5 (SD 15.0) for placebo and 0.5 (SD 2.0) for rituximab.
The intergroup differences were similar for counts of new lesions.
The researchers also reported that lesion counts at week 48 were virtually unchanged from values at week 24 for both patient groups.
From baseline to week 36, the mean change in lesion volume was an increase of 417.8 cubic mm (SD 1,358.4) for placebo, compared with a decrease of 175.4 cubic mm (SD 1,187.6) for rituximab (P=0.008).
Effects on relapses were a secondary outcome. The researchers found that 40% of placebo patients had experienced relapses by week 48 compared with only 20.3% of patients on rituximab (P=0.04).
Except for infusion-related events after the first dosing, adverse effects were generally similar for both treatments. Certain infections were more common with rituximab, including urinary tract infections (14.5% versus 8.6%) and sinusitis (13% versus 8.6%). On the other hand, infection-associated serious adverse events were seen in 5.7% of patients receiving placebo, compared with 2.9% of the rituximab group.
Substantially more patients in the placebo group discontinued treatment prematurely (40% versus 15.9%), the researchers said.
About a quarter of patients developed antibodies against rituximab, a chimeric molecule that retains some murine elements.
Genentech spokeswoman Nikki Levy said that although these anti-drug antibodies had no apparent clinical effects, the finding helped motivate the company's decision to pursue ocrelizumab in place of rituximab for relapsing-remitting multiple sclerosis.
Ocrelizumab is a humanized anti-CD20 antibody. Levy said Genentech believes it "may offer safety advantages," and the company is now discussing a phase II trial design with the FDA for the drug.
Further complicating the situation is a legal dispute between Genentech and Biogen Idec involving both agents. The partners disagree about certain aspects of the clinical development program and have taken the dispute to arbitration.
Levy said a ruling could include an injunction blocking clinical trials of rituximab and/or ocrelizumab, but would not comment on when a ruling may come down.
Genentech is now conducting a phase II/III trial of rituximab in primary progressive MS.
In an accompanying editorial, Henry McFarland, M.D., of the National Institute of Neurological Disorders and Stroke in Bethesda, Md., observed that the HERMES data were wanting in some important respects.
"A phase II trial leaves many questions unanswered; these include the duration of the treatment effect, the effect of progression of disability, and -- most important -- the types of adverse events that may occur at low frequency," he wrote.
Nevertheless, the short-term efficacy as measured by lesion accounts was "remarkable," he said.
He also agreed with the researchers that the findings confirm the importance of B cells in MS pathology and their value as a drug target.
How rituximab works in multiple sclerosis remains unclear. The researchers said it does not seem to involve direct reduction of B-cell-produced autoantibodies.
They suggested that another function of B cells, antigen presentation, is more likely to account for rituximab's efficacy.
They also suggested that another mechanism may involve inhibition of cytokines released from B cells that promote T-cell activity.
Multiple sclerosis affects about 400,000 people in the U.S. Some 85% of cases begin with the relapsing-remitting form, but about one-third of these eventually become fully progressive, according to a 2001 Institute of Medicine report.
Currently, rituximab is approved for treating several forms of non-Hodgkin's lymphoma and as second-line biologic therapy in rheumatoid arthritis.