Navigating Vaccines and KESIMPTA

This educational video is sponsored by Novartis Pharmaceuticals Corporation. The speakers in this program have been compensated by Novartis to conduct this presentation.

Kesimpta offers power, precision, and flexibility for your adult RMS patients.

Please see full Prescribing Information, including Medication Guide, accompanying this video and additional Important Safety Information on the adjacent panel of this video

Dr Nicholas

Tonight we're going to talk about why KESIMPTA may be a good option for some of your patients with relapsing forms of multiple sclerosis

So, as you know, KESIMPTA is indicated for the treatment of relapsing forms of MS, and this includes clinically isolated syndrome, relapsing-remitting disease, as well as active secondary progressive disease in adults

Now prior to starting KESIMPTA, we want to make sure that we rule out active hepatitis B virus infection in our patients, because that would be a contraindication of starting

And it is administered via Sensoready® Pen. There are loading doses, and then it's given once monthly by self-administration via sub Q injection

All right, Dr West. What are the vaccine recommendations for patients who want to start KESIMPTA?

Dr West

So the idea here is to give you a little bit of background about the kinds of vaccines that are out there, but then also talk about this specific recommendations with regard to KESIMPTA

So just to talk about how vaccines work in general, I know this is review for everyone in the audience but it's, I think, it's always helpful. B cells are a part of a complex immune response to both viruses and vaccinations. T cells are also involved and play a fundamental role in the viral infections, in viral infections by helping B cells to produce antibodies. In addition, they also orchestrate the infected cells to reduce the viral burden. So B cells and T cells are both very important in our response to both the virus and the vaccine itself

So live-attenuated vaccines—that term is also sometimes synonymous with live vaccines. These are ones that contain a weakened or an attenuated version of the actual living virus or bacteria. Because they're so similar to the natural infection, these do create a strong and long-lasting immune response, which is a positive, but live-attenuated vaccines, we don't really want to be having those when you have a B-cell depleting medication on on board. So in ASCLEPIOS I and II, concomitant treatment with non-live vaccine was permitted, and some patients did actually receive those, the non-live vaccines, but we really don't want to be giving live or live-attenuated vaccines to patients on KESIMPTA. Just to give you a sense for what those might be, common ones include chickenpox or measles vaccines

Viral vector vaccines, which is kind of a newer one out there, it's actually one of the COVID-19 vaccines out there as a viral vector vaccine, these instead of actually preventing infection by modifying the specific virus itself that causes the infection, a viral vector vaccine relies on modifications to a different virus, and then that viral vector enters the body’s cells, stimulates an immune response, and the idea is that it's stimulating an immune response to the intended virus without actually introducing the actual virus. These vaccines either use live vectors that replicate, but are often attenuated, or they are non-replicating considered non-live, including the COVID-19 vaccine that is currently in use in the United States of America

Inactivated vaccines are one that we're very, very familiar with. These are things like hepatitis A, polio, influenza, and these are an inactivated virus or bacteria that is sort of rendered unable to enter cells or replicate, and the idea is that they usually don't provide immunity that is as strong as the live vaccines but are generally considered to be maybe a little bit safer. And so, these are the ones, these inactivated vaccines are the ones you, you can take in patients who are taking KESIMPTA but, again, we will come back to the next slide, in theory, it’s better to do it a little bit before

And the last one is sort of the newer category that we're much more familiar with now in 2021, and those are the mRNA vaccines. And this is a type of non-live vaccine that does not contain a virus. One of the upsides to this is you're not actually giving the virus to the individual. The way this works is that the mRNA translation produces a protein specific to the virus and that that should trigger an immune response. And again, any vaccine used in patients with KESIMPTA should be administered in accordance with the KESIMPTA Prescribing Information

So we talked a little bit about what we do in a KESIMPTA patient. And again, this is where we're rehashing this again, but the idea is for live or live-attenuated vaccines, ideally you'd want to give them at least 4 weeks before starting KESIMPTA. For the non-live and activated vaccines again up to 2 weeks out so that includes all of your COVID, SARS-type vaccinations

In the ASCLEPIOS I and II pivotal studies, concomitant treatment with these non-live vaccines was permitted, but it's important to understand that the vaccine response weren’t really studied, so we don't know if this affects it—it's possible that it might, we don't we don't know how that alters the immune response

In infants and mothers, we’re again reiterating this from before, treated with KESIMPTA during pregnancy, we really shouldn't be giving the live or live-attenuated vaccines before confirming the recovery of B-cell counts. So this is specifically talking about measles mumps rubella type vaccines, because the measles is live-attenuated and before, if you have a child who's born after the mother was exposed to KESIMPTA, you should really make sure that those B cells are back before administering that particular vaccine

The currently available COVID-19 vaccines on the market that are made by Pfizer, BioNTech, Moderna, and Jannsen are all considered to be non-live vaccines, and therefore you'd fall under the recommendation of trying to get it in there at least 2 weeks before starting KESIMPTA

Dr Nicholas

We'll go ahead and walk through the things that we need to check prior to getting a patient started

So I know we discussed earlier that we need to make sure our patients don't have active hepatitis B virus. Active hep B would be confirmed by a positive hepatitis B surface antigen and an anti-HBV test

Patients who are positive for core antibody would need to be evaluated by hepatology prior to starting, or GI

We also check baseline serum immunoglobulin and, if you find that your patient has low immunoglobulins, it is recommended that you consult with an immunology expert prior to starting treatment

And then, again, just a quick reminder to what Dr West discussed earlier, we want to make sure that for any live or live-attenuated vaccine, we give it at least 4 weeks prior to starting KESIMPTA and they're not recommended for treatment for use during treatment with KESIMPTA and until we've seen full B-cell repletion after stopping

Then for inactivated vaccines, again, make sure you give those at least 2 weeks prior to initiation of KESIMPTA

Can you tell us a little bit about the effect of KESIMPTA on immunoglobulin levels?

Dr West

So yeah, so first off, if you're new to the B-cell depletion sort of way of treating this condition, this is something that we think about a great deal, because remember, B cells and T cells interact to help generate antibodies. So we always want to know if the B-cell? depleting medication is going to dip the antibodies in a way that might be harmful to the patient

So, the changes in serum IgM and IgG levels were assessed up to week 120 in a subgroup analysis of the ASCLEPIOS studies. Serum samples were collected at week 4, and then at week 12, and then every 12 weeks throughout the remainder of the study

A reduction in IgM levels from baseline was observed in both treatment groups in both studies. In 14.3% of the patients in ASCLEPIOS I and II trials, treatment with KESIMPTA resulted in a decrease in serum IgM that reached a value below 0.34. The average IgM levels remained well within the reference ranges of 0.23 to 2.59 g/L for patients—and this was patients age 16-19 — and it was even higher, the levels are a little higher at 0.4 to 2.3 in patients over 19. But the key there is that the average levels were generally within the reference range, and there was a small percent that dip below

And with the average IgG levels, same idea, they remained well within

the reference ranges of 5.49 to 15.84 g/L, you can see there. And this is a little bit different for patients over 19 but, again, stayed within the average range. And KESIMPTA was associated with a decrease of 4.3% in the mean IgG levels after 48 weeks of treatment and an increase of 2.2 after

96 weeks, so there was an initial dip and then it kind of came back up

So the key here is that correlation with immunoglobulin levels and infections was then evaluated, because the real question is: IgM levels dip a little bit; IgG levels dip a little bit; did it have any impact on the patients? And this is what was seen

Serum samples again were collected week 4, week 12, and then every 12 weeks, and the risk of serious infections was low in patients with IgM and IgG levels below the lower limit of normal in both treatment groups. And that's true for, in the KESIMPTA, it was 1.2% versus 0% with related to IgM, and in the IgG it was 2.2% vs 0.9% for IgG and teriflunomide

After the first drop of IgM levels, there were 2 patients that experienced significant infections (influenza, urinary tract infection), and after the first drop of IgG levels below the lower limit of normal, 3 patients experienced serious infections, upper respiratory infection, urinary tract infection, and pneumonia

Dr Nicholas

Thanks for that more granular detail there. So, in light of that data, Dr Williams, can you share with us your recommendation for monitoring immunoglobulin levels in patients on KESIMPTA?

Dr Williams

Absolutely. So the short answer is before, during, and after. So certainly we want to know a baseline before patients started treatment, and they need to be monitor those levels during the course of treatment, and then, if the levels became, you know, too low and it led to discontinuation, those levels would need to be monitored after treatment was discontinued

And certainly, this is especially important for patients who may have recurrent infections, or experience opportunistic infections, which may lead to discontinuation of therapy

And they should be, the immunoglobulin should be monitored after discontinuation of therapy until full B-cell repletion occurs

Important Safety Information

Infections

Delay KESIMPTA administration in patients with an active infection until the infection is resolved. Vaccination with live-attenuated or live vaccines is not recommended during treatment with KESIMPTA 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 immunoglobulins at the beginning, during, and after discontinuation of treatment with KESIMPTA until B-cell repletion. Consider discontinuing KESIMPTA 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 at least 6 months after the last dose