“MS used to be a orphan disease. Interferon-beta-1a (Avonex) was licensed by the FDA under the orphan drug legislation. What is an orphan disease? Orphan diseases are rare diseases that only affect a small percentage of the population. Orphan drug acts were put in place to incentivise drug companies to take the risk and develop drugs for these diseases. MS is no longer an orphan disease; sales of DMTs for MS are close to $15billion a year. In the beginning the Pharma companies in the MS space were relatively small, but as the market expanded the big beasts started to arrive; Novartis, Sanofi, Roche and now GSK. GSK is developing ofatumumab for MS; the stunning phase 2 results are presented below.”
|The Big Beast: GSK joins the fray|
“I predict that the class of monoclonal antibodies that deplete B-cells (anti-CD20 and anti-CD19) will be the real game-changers in the field; they come with very high-efficacy and have a relatively good safety profile. There are, however, several unanswered questions around their use in MS. (1) How should they be used; as maintenance therapies or as induction therapies. A maintenance therapy requires the drug to be given continuously and indefinitely. In comparision, an induction therapy require a treatment period of say 2 years and then a watch and see approach with re-treatment given if MS disease activity reemerges. No prizes for guessing what class of drug Pharma want. The distinction between maintenance and induction is not trivial and affects pricing and reimbursement. In short it gives Pharma executives a big headache. (2) How safe is long-term B cell depletion? Can you survive without any circulating B cells for 30 or 40 years? I suspect you can as there are a large number of hereditary disorders, which affect B cells. We simply treat these patients with immunoglobulin or antibody replacement therapy. (3) Do anti-CD20s work in non-relapsing progressive MS? The Roche ocrelizumab PPMS trial will address this question. (4) How do B cell depleters work? Are they working via an anti-EBV mechanism? As you know EBV resides in B-cells and B-cell depleting agents are very good at suppressing EBV viral loads. In fact Rituximab, which is very effective in MS, is the only licensed anti-EBV drug on the market; it has a license for EBV-associated post-transplant lymphoproliferative disease. (5) Do other drugs and strategies that transiently deplete B cells working in the same way, for example mitoxantrone, cyclophosphamide, alemtuzumab, cladribine, bone marrow transplant, etc.? I love it when science results in more questions be asked than it answers; innovation feeds innovation.”
“Let’s celebrate these results. Well done to the investigators and MSers for participating in this trial. And thank you Genmab and GSK; it is good to have another kid on the block.”
Epub: Sorensen et al. Safety and efficacy of ofatumumab in relapsing-remitting multiple sclerosis: A phase 2 study. Neurology. 2014 Jan 22.
OBJECTIVES: We present the first study to explore safety and efficacy of the human CD20 monoclonal antibody ofatumumab in relapsing-remittingmultiple sclerosis (RRMS).
METHODS: In this randomized, double-blind, placebo-controlled study, patients received 2 ofatumumab infusions (100 mg, 300 mg, or 700 mg) or placebo 2 weeks apart. At week 24, patients received alternate treatment. Safety and efficacy were assessed.
RESULTS: Thirty-eight patients were randomized (ofatumumab/placebo, n = 26; placebo/ofatumumab, n = 12) and analyzed; 36 completed the study. Two patients in the 300-mg group withdrew from the study because of adverse events. No unexpected safety signals emerged. Infusion-related reactions were common on the first infusion day but not observed on the second infusion day. None of the patients developed human anti-human antibodies. Ofatumumab was associated with profound selective reduction of B cells as measured by CD19+ expression. New brain MRI lesion activity was suppressed (>99%) in the first 24 weeks after ofatumumab administration (all doses), with statistically significant reductions (p < 0.001) favoring ofatumumab found in new T1 gadolinium-enhancing lesions, total enhancing T1 lesions, and new and/or enlarging T2 lesions.
CONCLUSIONS: Ofatumumab (up to 700 mg) given 2 weeks apart was not associated with any unexpected safety concerns and was well tolerated in patients with RRMS. MRI data suggest a clinically meaningful effect of ofatumumab for all doses studied. Results warrant further exploration of ofatumumab in RRMS.