Jason Freeman, MD, MBA, and Brandon Brown, PharmD, discuss the poster “Five-Year Safety of Ofatumumab in People Living with Relapsing Multiple Sclerosis” presented at AAN 2023. Sponsored By Novartis.
Jason Freeman, MD, MBA: Welcome to AAN 2023. I'm your host, Dr Jason Freeman, Medical Director, Novartis Medical Affairs, providing you with updates from AAN 2023. The information herein is provided for disease educational purposes only, and is not intended to be, nor does it imply medical or diagnostic advice.
Indications and usage of ofatumumab. Ofatumumab is a CD20-directed cytolytic antibody indicated for the treatment of relapsing forms of multiple sclerosis to include clinically isolated syndrome, relapsing remitting disease, active secondary progressive disease in adults. Contraindications: active HPV infection. Warnings and precautions: infections: delay ofatumumab administration in patients with an active infection until the infection is resolved. Vaccination with live attenuated, or live vaccines is not recommended during the treatment with ofatumumab and after discontinuation until B-cell repletion. Injection-related reactions: management for injection related reactions depends on the type and severity of the reaction. Reduction in immunoglobulins: monitor the level of immunoglobulin at the beginning, during and after discontinuation of the treatment with ofatumumab until B-cell repletion. Consider discontinuing ofatumumab if a patient develops a serious opportunistic infection or recurrent infections if immunoglobulin levels indicate immune compromise. Fetal risk: may cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for the 6 months after stopping ofatumumab. Adverse reactions: most common adverse reactions incidents (greater than 10%) are upper respiratory tract infection, headache, injection-related reactions, and local injection site reactions. Please see the full prescribing information for additional information.
Joining me today is Dr Brandon Brown, a Medical Director also with Novartis Medical Affairs.
Brandon Brown, PharmD: Thanks for having me, Dr Freeman.
Jason Freeman, MD, MBA: Welcome. We will discuss key takeaways from the poster titled “Five Year Safety of Ofatumumab in People with Relapsing Multiple Sclerosis.” So, Brandon, why do neurologists want to examine long-term safety data on DMTs in MS?
Brandon Brown, PharmD: Sure. It's an interesting question. Remember that patients with multiple sclerosis are diagnosed in their early 30s or 40s. So, they often face many decades of potential exposure to these medications. And for that reason, of course, we need to know how these patients will do long-term from a safety perspective. Also, these medications are immunosuppressive or immunomodulatory in nature. So, we always have to be concerned about things such as infections, malignancies, et cetera, which, of course, take sometimes years to surface. So, it's important to follow these patients long-term.
Jason Freeman, MD, MBA: Can you tell us more about how the data in this particular study was generated?
Brandon Brown, PharmD: Sure. These data come from a number of different phase 3 and 3B studies. The two ASCLEPIOS studies were our pivotal studies. These were the trials that brought the drug to the market. These were multinational studies enrolling a couple thousand patients, actually. Another study called APOLITOS was a study that took place in Eastern Asia, specifically in Japan and Russia, where some of the health authorities actually require placebo-controlled studies. So that was a placebo-controlled study. And then there's another study called APLIOS, which was our bioequivalent study, which enabled us to bring the drug to market in the form of an autoinjector as opposed to a pre-filled syringe. So, all of these studies roll into the ALITHIOS study, which is our extension study. And we follow these patients over long periods of time to watch out for safety concerns.
Jason Freeman, MD, MBA: So, it's not just one particular study, but an aggregate really focused on safety.
Brandon Brown, PharmD: Correct.
Jason Freeman, MD, MBA: How does this five-year data compare to the previously published four-year data released sometime last year?
Brandon Brown, PharmD: These data are largely consistent with the four-year data from the perspective of infections and malignancies. We have not seen an increased risk in these patients over the five-year period. From an immunoglobulin perspective - this is an important area to look at, as well. So, these drugs can affect immunoglobulin levels, and it's something that we've recognized for years with these types of therapies. Immunoglobulin M is affected slightly, it does go down over time in these patients, but there's really never been a correlation to infections with low immunoglobulin M. It’s more the IgG, or immunoglobulin G, that we're more concerned with. Low IgG has been associated with serious infections, and we have not seen a decrease in the mean concentration of IgG in these patients over a five-year period of time. So, it's something we're excited about. We will continue to follow that. But that's what we've seen thus far.
Jason Freeman, MD, MBA: Can you highlight some of the clinical implications for neurologists and patients out there considering these therapies? What do we need them to know about ofatumumab?
Brandon Brown, PharmD: Sure. What we do know is this drug is well tolerated. We have not seen any new safety signals over the five years. And there's a favorable benefit-risk profile, we believe. So, you think about these patients that enroll in these trials, they're often having a relapse every year or two relapses every two years. That's typically the requirement to get into these trials. And what we're seeing is these patients are now having relapses less than once every 10 years in most cases. So, it remains to be very effective as well in these patients.
Jason Freeman, MD, MBA: Dr Brown, thanks for your time today. We appreciate you being here and sharing your knowledge for this particular poster.
Brandon Brown, PharmD: Pleasure was all mine.
Jason Freeman, MD, MBA: Thank you for watching AAN 2023 updates from Novartis US Medical Affairs.
Transcript Edited for Clarity