Genentech and Roche announced that the Food and Drug Administration has granted Breakthrough Therapy Designation for the investigational medicine ocrelizumab (Ocrevus™) for the treatment of people with PPMS. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening disease and for which preliminary clinical evidence suggests that the drug may demonstrate substantial improvement over existing therapies. Remember that PPMS has no approved therapies.
Breakthrough Therapy Designation was granted to ocrelizumab based on positive results form a pivotal Phase III study (called ORATORIO) which showed treatment with ocrelizumab significantly reduced disability progression and other markers of disease activity compared with placebo in patients with PPMS. Top-line results were of ORATORIO were presented at the 31th ECTRIMS conference in October 2015.
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Showing posts with label Monoclonal Antibodies. Show all posts
Showing posts with label Monoclonal Antibodies. Show all posts
Thursday, February 18, 2016
Tuesday, October 13, 2015
Positive Trial Results for Ocrelizumab in Primary Progressive MS
After lots of hype and buildup ahead of the conference, the pharmaceutical company Roche-Genentech finally revealed a bit more than simply “positive results” from three pivotal Phase III studies of the experimental MS therapy ocrelizumab in relapsing MS and primary progressive MS (PPMS). While relapsing MS has 13 approved therapies and other treatments which are used off-label, such as rituximab, effective treatment for PPMS has continued to be elusive.
What is ocrelizumab?
Ocrelizumab is a humanized (10 percent mouse, 90 percent human-derived) monoclonal antibody designed to target a selective group of immune cells - CD20+ B-cells - which have been implicated in the damage of myelin, the fatty substance that protects nerve cells and helps to speed the transmission of nerve signals throughout the body. In clinical trials, ocrelizumab 600 mg was administered by intravenous (IV) infusion every six months, given as two 300 mg infusions spaced two weeks apart in the ORATORIO trial, while repeat rounds in the OPERA I and II trials were given as a single 600 mg dose infusion.
Ocrelizumab works in the same way as rituximab (Rituxan), a chimeric (100 percent mouse-derived) monoclonal antibody that attaches to CD20 cell surface proteins and causes certain B-cells (but not stem cells or plasma cells) to self-destruct. Rituxan is used to treat rheumatoid arthritis (RA), non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), granulomatosis with polyangitis (GPA) and microscopic polyangitis (MPA). Rituxan is also used off-label for a number of other autoimmune diseases including MS and neuromyelitis optica (NMO). Patents protecting Rituxan (jointly marketed by Genentech and Biogen) from generic competition begin to expire in 2015.
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Is Ocrelizumab The Next Game-Changer in MS Treatments?
What is ocrelizumab?
Ocrelizumab is a humanized (10 percent mouse, 90 percent human-derived) monoclonal antibody designed to target a selective group of immune cells - CD20+ B-cells - which have been implicated in the damage of myelin, the fatty substance that protects nerve cells and helps to speed the transmission of nerve signals throughout the body. In clinical trials, ocrelizumab 600 mg was administered by intravenous (IV) infusion every six months, given as two 300 mg infusions spaced two weeks apart in the ORATORIO trial, while repeat rounds in the OPERA I and II trials were given as a single 600 mg dose infusion.
Ocrelizumab works in the same way as rituximab (Rituxan), a chimeric (100 percent mouse-derived) monoclonal antibody that attaches to CD20 cell surface proteins and causes certain B-cells (but not stem cells or plasma cells) to self-destruct. Rituxan is used to treat rheumatoid arthritis (RA), non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), granulomatosis with polyangitis (GPA) and microscopic polyangitis (MPA). Rituxan is also used off-label for a number of other autoimmune diseases including MS and neuromyelitis optica (NMO). Patents protecting Rituxan (jointly marketed by Genentech and Biogen) from generic competition begin to expire in 2015.
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Is Ocrelizumab The Next Game-Changer in MS Treatments?
Tuesday, August 25, 2015
Novartis Obtained MS Rights to Ofatumumab
What is ofatumumab?
Ofatumumab is a B-cell depleting monoclonal antibody therapy that targets CD20+ B-cells. Multiple sclerosis is known to be affected by T-cell activity, but is increasingly understood to be connected to B-cell activity in the immune system. B-cells are lymphocytes produced in the bone marrow.
B-cell depleting therapies and MS
Each of the investigational therapies that target CD20+ B-cells are cytotoxic, meaning that they bind to CD20 receptors on the cell surface and cause the cell to self-destruct. The rapid depletion of these specific B-cells is proving to be an effective treatment for MS.
Ofatumumab (Arzerra), a fully human MAB, has been studied in a small Phase IIa clinical trial involving 38 patients with relapsing-remitting MS. Results from the trial showed that intravenous ofatumumab (at each of three different doses being tested, given by infusions separated by two weeks) reduced total number of new brain lesions by up to 90% in 4-12 weeks. Compared to placebo, ofatumumab did not increase serious adverse events; however two patients in the 300-mg dosage group dropped out of the study because of adverse events. In light of these positive results, ofatumumab should be ready to move into Phase 3 trials.
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Novartis to Pay GSK $1B+ for Ofatumumab to Treat MS
Ofatumumab is a B-cell depleting monoclonal antibody therapy that targets CD20+ B-cells. Multiple sclerosis is known to be affected by T-cell activity, but is increasingly understood to be connected to B-cell activity in the immune system. B-cells are lymphocytes produced in the bone marrow.
B-cell depleting therapies and MS
Each of the investigational therapies that target CD20+ B-cells are cytotoxic, meaning that they bind to CD20 receptors on the cell surface and cause the cell to self-destruct. The rapid depletion of these specific B-cells is proving to be an effective treatment for MS.
Ofatumumab (Arzerra), a fully human MAB, has been studied in a small Phase IIa clinical trial involving 38 patients with relapsing-remitting MS. Results from the trial showed that intravenous ofatumumab (at each of three different doses being tested, given by infusions separated by two weeks) reduced total number of new brain lesions by up to 90% in 4-12 weeks. Compared to placebo, ofatumumab did not increase serious adverse events; however two patients in the 300-mg dosage group dropped out of the study because of adverse events. In light of these positive results, ofatumumab should be ready to move into Phase 3 trials.
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Novartis to Pay GSK $1B+ for Ofatumumab to Treat MS
Tuesday, February 2, 2010
Monoclonal Antibodies in Development for MS
What are some monoclonal antibody treatments in development for MS?
At present, several additional monoclonal antibodies are being studied as investigational treatments for MS. They are not currently available for routine use in the treatment of MS.
Rituximab (Rituxan®) is a monoclonal antibody directed at B-cells (CD20+ B-cells) and have been reported recently to be efficacious in treatment of relapsing-remitting MS. Studies in primary progressive MS did not produce statistically significant results. This drug is FDA approved for treatment of rheumatoid arthritis and non-Hodgkin’s lymphoma. (Read more about Rituxan in Rituximab Infusion: My First Experience)
[Note: I believe that ofatumumab, a fully human monoclonal antibody focused on CD20+ B-cells, will replace rituximab in studies in MS. See listing in clinicaltrials.gov.]
Alemtuzumab (Campath®) is another monoclonal antibody directed at lymphocytes (CD52+ B-cells) which is under continued investigation for treatment in MS. Campath was found to be more effective than Rebif in early relapsing-remitting MS. Both rituximab and alemtuzumab are associated with longer-term immunosuppression (6 to 12 months). Serious immunological and infectious complications have occurred with these agents.
Daclizumab (Zenapax®) is FDA approved for the treatment of kidney transplant rejection. Zenapax is a humanized monoclonal therapy which targets CD25+ T-cells and blocks IL-2. It is off-label for MS and people with relapsing-remitting and transitional MS are treated with this agent. Most often these people have failed several other treatments. Efficacy has been demonstrated in off-label experience, two small phase II studies, and a larger multi-center phase II study. Currently, a longer duration multi-center phase II trial is in progress in Europe. Rash, fever, and occasional overgrowth of lymph nodes have been observed in people on long-term therapy with this drug.
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Monoclonal Antibodies: Treatments in Development for MS
Wednesday, January 20, 2010
Rituxan, Tysabri, Zenapax are Monoclonal Antibodies
Monoclonal antibodies (MABs) are a type of biological therapy which have an ability to bind to selective molecules found on the cell surface of lymphocytes. (‘Monoclonal’ just means all one type.) Monoclonal antibody therapy uses antibodies that are made in the lab rather than by a person's own immune system. This type of treatment is used in inflammatory conditions such as MS, rheumatoid arthritis, or malignant diseases such as leukemia and lymphoma.
The first monoclonal antibodies (MABs) were made entirely from mouse cells. One problem with this is that the human immune system will see these antibodies as foreign (because they're from a different species) and then will mount a response against them. In the short term, this can sometimes cause allergic-type reactions. In the long term, it means that the antibodies may only work the first time they are given; after that, the body's immune system is primed to destroy them before they can be helpful.
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Monoclonal Antibodies: What are they?
The first monoclonal antibodies (MABs) were made entirely from mouse cells. One problem with this is that the human immune system will see these antibodies as foreign (because they're from a different species) and then will mount a response against them. In the short term, this can sometimes cause allergic-type reactions. In the long term, it means that the antibodies may only work the first time they are given; after that, the body's immune system is primed to destroy them before they can be helpful.
Read this post in its entirety:
Monoclonal Antibodies: What are they?
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