KESIMPTA® and Treatment-Naïve Patients With RMS

[Voice Over]

The speakers have been paid by Novartis Pharmaceuticals Corporation (NPC) to conduct this presentation.

[Dr Shin]

KESIMPTA is indicated for the treatment of relapsing forms of MS, to include clinically isolated syndrome, relapsing-remitting disease, as well as active secondary progressive disease, in adults. Warnings and precautions include Infections, Injection-Related Reactions, Reduction in Immunoglobulins, and Fetal Risk. Most common adverse reactions (incidence greater than 10%) are upper respiratory tract infection, injection-related reactions, headache, and local injection-site reactions. Please see additional Important Safety Information throughout this presentation and accompanying full Prescribing Information.

[Dr Bass]

Dr Shin, from your perspective, why are physicians sometimes hesitant to initiate high efficacy therapy early in the disease course?

[Dr Shin]

Well, I think the evolution of MS treatment options has contributed to these perceptions and hesitancy. Research and development aim to achieve greater efficacy than what was available with earlier therapies from the 1990s. Unfortunately, pursuing higher efficacy therapies created concern among some clinicians that the benefit-to-risk ratio would become unbalanced and that new therapies could be associated with increased safety risks. As a result, some physicians in the MS space got nervous about the potential for unfamiliar risks associated with high efficacy treatment options. This led some physicians to start with an earlier, more familiar therapy and then, if needed, to escalate. But I think the data tells a different story

[Dr Bass]

I agree, Dr Shin. To your first point, I think some worry that if they throw an umbrella of high efficacy treatment over every patient, they may unnecessarily put patients at risk. And overall, clinicians want the benefit of treatment to always outweigh the risk

[Dr Shin]

How do your patients typically feel about initiating high efficacy therapy early?

[Dr Bass]

So, excellent question. In my experience, providers are more concerned about risk than the patients are. It's typically all about disability for my patients. If you put patients on a treatment that has data to show reduced disability progression, then they are generally more comfortable taking potential risks associated with an MS treatment

[Dr Shin]

Yeah, I agree. If you ask physicians to rank the importance of different topics associated with MS treatment and then ask patients to do the same, their answers don't always line up, which is interesting. I have to say, in my experience, sometimes patients do feel that safety is a primary concern. They'll often ask, "What's the catch?" You know, "What are the side effects going to be like? What's the risk I'm going to take now?". But there are times when I'm presenting MS treatment options to patients who, even at the time of diagnosis or during the first conversations, say, "You know, I really wanna nip this in the bud." They want to meet the disease with equal force. So, there isn't a uniform answer among all individuals in my practice

[Dr Bass]

Great point. And just to add to that, I find that if I go straight into talking about high efficacy treatment options without laying out the natural history of the disease, my patients aren't as receptive to a high efficacy therapy. Because of this, with any patient, but especially with treatment-naïve patients, I spend some time explaining the risk of the disease. Sometimes if the patient feels okay and they don't know what their MRI looks like, they may think that they don't need treatment to begin with, much less a high efficacy treatment. So I explain the natural history of the disease to them. I don't want to scare them, but I think that there's value in highlighting the potential for irreversible neurological damage that may occur with this disease. Once I gently inform patients that this is ultimately what happens, no matter where they start in terms of disability, it's a neurodegenerative disease, they seem more open to listening to my treatment recommendations

[Dr Shin]

So I'm curious to hear more about this discussion that you have with your patients. Could you share an example from your practice of a patient who was treatment naïve and started KESIMPTA?

[Dr Bass]

Of course. A particular patient comes to my mind. So, this adult patient was young and had a few lesions on her spinal cord and brain, and she presented with an active clinical relapse. When I saw this patient, I knew that the writing was on the wall. If left untreated or if sub-optimally treated, I pretty much would anticipate another clinical relapse or radiological evidence of lesion activity

[Dr Shin]

Right. That definitely sounds like someone in need of a proven, effective therapy. When you were discussing KESIMPTA as a potential treatment option, what were some of the first questions your patient had?

[Dr Bass]

Well, my patient first wanted to know if KESIMPTA was appropriate for her. And when my patients and fellow peers are asking about KESIMPTA, especially for treatment-naïve patients, it's very helpful for me to remind them that approximately 40% of patients in the ASCLEPIOS trials were actually treatment naïve

[Dr Shin]

Yeah. I think that may be surprising to some because I think some clinicians will reserve a therapy like KESIMPTA, something that was demonstrated to be a high efficacy in clinical trials compared to teriflunomide, for patients who are much more advanced in their disease and treatment journey

[Dr Bass]

•Can you tell us more of your thinking on why it is important to explore KESIMPTA with our treatment-naïve patients?

[Dr Shin]

Sure. So, in my practice, I like to provide my patients with a high efficacy therapy option earlier whenever appropriate. I suppose it's possible that there could be some individuals who have such mild MS that it wouldn't make a difference what therapy to initiate, but I think the problem is that I won't know who those patients are when I'm initially diagnosing and treating them. So, I feel like we should assume that we need to reduce disease progression in every patient as much as possible. So, for this reason, I opt for therapies that have demonstrated high efficacy in clinical trials, for example, KESIMPTA when compared to teriflunomide. And there is data to show that KESIMPTA can be considered for patients who are treatment naïve. So if you take a look at the pivotal trials data for KESIMPTA, which showed 58% relative reduction in annualized relapse rate, up to 98% relative reduction in MRI lesion activity, and up to 34% risk reduction in confirmed disability progression at 3 months vs teriflunomide

[Dr Bass]

Yes. I love the fact that KESIMPTA has the reduction in annualized relapse rate compared to teriflunomide. I tell my patients that reducing the risk of that next relapse could be critical. Because what if it results in extreme disease progression? Doing what I can to reduce relapse risk is huge because nobody can predict what might happen. Before we had MS treatments, patients might expect one relapse every year or every other year. With KESIMPTA, though, you're talking about potentially 1 relapse every 10 years, with a 58% relative reduction in annualized relapse rate versus teriflunomide. That's huge. Again, I cannot predict when my patients might have their next relapse, so I'd rather just try my best to reduce relapse risk for as long as I can. With KESIMPTA, because we have data showing a reduction in annualized relapse rate versus teriflunomide, it's easy for me to consider using KESIMPTA in my RMS patients. We have to remember that MS is a neurogenerative disease and what is lost cannot be regained

[Dr Shin]

Right. And I always like to turn back to the data. And in the 5-year extension study, we see that for those who initiated treatment on KESIMPTA compared to those who switched from teriflunomide to KESIMPTA, there is a 3-month disability progression event rate of 21.7% versus 24.8%, respectively. And looking at cumulative 6-month disability progression, that was lower in patients who stayed on KESIMPTA, with an 18.5% vs 21% event rate in patients who switched from teriflunomide

[Dr Shin]

So I'd like to come back to something that we touched on earlier when discussing why some clinicians are hesitant to initiate high efficacy therapy in treatment-naïve patients, and that's safety risk. What safety concerns do your patients typically have about initiating KESIMPTA?

[Dr Bass]

Most of my patients are concerned about the risk of infection. Those conversations regarding infection risk are pretty straightforward since I can speak to the data that show that the overall rate of infections and serious infections in patients treated with KESIMPTA was similar to teriflunomide, at 51.6% vs 52.7%, and 2.5% vs 1.8%, respectively. After I do what I can to address any concerns, I'll then ask if there are any other apprehensions. Just like this patient case, much of the time my patients look to me for that reassurance, and I want them to know that I have reviewed the data and have experience treating patients like them, so I feel confident in selecting KESIMPTA

[Dr Shin]

Yeah, I also like what I see from the pivotal trials where KESIMPTA and teriflunomide had comparable safety profiles. Particularly of interest is that the pooled data from both clinical trials show that treatment discontinuation rates due to adverse events were similar between KESIMPTA, at 5.7%, and teriflunomide, at 5.2%7. So, to me, that's an important aspect of the safety profile

[Dr Shin]

I also want to highlight that, in the 5-year extension analysis, we haven't seen any new safety signals. However, COVID-19 was the most common infection contracted at 30.3% of all infections. Overall, it does appear that the nature and frequency of the most common AEs were comparable with those reported in ASCLEPIOS I and II. The most common adverse events were infections – COVID-19, nasopharyngitis, upper respiratory tract infections, and urinary tract infections. Most infections resolved without discontinuing KESIMPTA treatment. In addition, the exposure-adjusted incidence rate for malignancies did not increase over time in the overall KESIMPTA population

[Dr Shin]

Also, the 5-year data have shown that IgG levels remained stable over time while IgM levels declined but remained above the lower limit of normal

[Dr Bass]

I think I speak for most clinicians when I say that we are happy whenever we have these additional years of safety data to consider. Hopefully, these extensions continue to collect safety data over time so that clinicians and our patients can be informed about the effects of continued KESIMPTA use

[Dr Shin]

So now I'd like to focus in on your treatment-naïve patient. What else can you tell me about your treatment-naïve patient and their safety concerns with initiating KESIMPTA?

[Dr Bass]

Well, my treatment-naïve patient is a little different compared to my average patient. While most of my patients are typically concerned with infection risk or possibly malignancy, she was more concerned with specific adverse events, including headache, since she has a history of migraines. She was also concerned with local injection-site reactions because she lives in a warm climate where she likes to wear shorts or swimsuits and wouldn't want bruising to show. In this case, I reassured her that while 2 patients treated with KESIMPTA reported serious injection-related reactions, the incidence of injection-related reactions is highest with the first injection at 14.4% and decreases with subsequent injections. By the third dose, less than 3% of patients typically experience injection-related reactions. The most frequently reported symptoms, occurring in ≥2% of patients, included fever, headache, myalgia, chills, and fatigue

[Dr Shin]

So how is your patient doing on KESIMPTA?

[Dr Bass]

She complained of some additional headaches. The headaches were managed and so far, no other concerns. Clinically, the new baseline MRI looks good, all the active enhancing lesions are gone, no new lesions, and there hasn't been worsening of her lesions. So, we are in good shape for right now

[Dr Shin]

I'm glad to hear your patient is doing well on KESIMPTA. And it's reassuring to hear that the efficacy and safety seen in the clinical trials align with your patient's real-world experience. So, before we wrap up here, what final thoughts would you like to share regarding KESIMPTA for treatment-naïve patients and the safety data up to 5 years?

[Dr Bass]

With treatment-naïve patients, I focus on reminding them that whatever is lost cannot be regained. Even at diagnosis, we could already be behind from the time they had their first MS symptom, which was unbeknownst to them. Therefore, I consider KESIMPTA for most of my patients with MS, including recently diagnosed, treatment-naïve patients. I think that once I provide my treatment-naïve patients with that perspective, it really helps them to feel confident in moving forward with our treatment plan.

[Narrator]

Important Safety Information

Contraindication

KESIMPTA is contraindicated in patients with active hepatitis B virus infection

Infections

Serious, including life-threatening or fatal, infections have been observed during and following completion of treatment with anti-CD20 B-cell depleting therapies. 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