Scientific & Clinical Evidence on Early Initiation of KESIMPTA

[Voice Over]

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

[Dr Smoot]

What is the right time to initiate high efficacy therapy?

[Dr Williams]

Well, I am definitely an advocate for using high efficacy therapy early. So, in my practice, I aim to minimize disease activity by placing patients on what I think will be an effective therapy for them as early as possible. This is often a treatment that has demonstrated high efficacy in clinical trials, for example, KESIMPTA when compared to teriflunomide

[Dr Williams]

What are your thoughts on initiating KESIMPTA early in your patients' treatment course?

[Dr Smoot]

Today, we have many options for treating relapsing forms of MS. So, I like to provide at least two or three treatment options for consideration before starting a new treatment. I discuss how each medication works, and each medication's efficacy and safety profile. Then I'll typically give patients some time to think about their options before moving forward. One of the treatment options I frequently present to patients is KESIMPTA. KESIMPTA is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. Now, it's important to note that the warnings and precautions include Infections, Injection-Related Reactions, Reduction in Immunoglobulins, and Fetal Risk. Most common adverse reactions, with an incidence greater than 10%, are upper respiratory tract infection, headache, injection-related reactions, and local injection site reactions. Please see additional Important Safety Information throughout this presentation and accompanying full Prescribing Information. So, in the Phase 3 ASCLEPIOS I and II clinical trials of KESIMPTA versus teriflunomide, more than 80% of individuals were either treatment naïve or previously treated with one commonly used first-line therapy. Because of this, I feel very comfortable initiating KESIMPTA in the early phases of MS, whether the patient has some poor prognostic factors or if the patient only has mild disease

[Dr Williams]

I completely agree. I discuss KESIMPTA early on for my patients as well. It is a great treatment option for my patients because of the clinical evidence supporting its use

[Dr Williams]

Now, not all of our patients are treatment naïve. Some may have more established disease and experience with some form of treatment and now need to make a change for one reason or another. What do you consider when you or a patient feels it is time to change therapies?

[Dr Smoot]

Well, patients may have many reasons to change therapies. For example, They may want a different medication that fits with their lifestyle or meets new insurance coverage requirements. Also, a change in therapy may be warranted if a patient isn't tolerating their current therapy. An example could be a patient who is experiencing side effects that are resulting in missed doses, or worse, a discontinuation. Plus, if they are having worsening disease activity, then we start to have a discussion about making a transition to a different therapy.

[Dr Williams]

So, can you describe a patient case in which you changed their MS therapy to KESIMPTA?

[Dr Smoot]

Recently, I saw a 44-year-old female patient, Jane, who has had MS for approximately 3 years. Unfortunately, she relapsed and had a new lesion. At that time, we discussed transitioning her to a different medication. I decided to start Jane on KESIMPTA because of the Phase 3 clinical studies that included patients with at least one relapse in the previous year or the presence of a T1 gadolinium-enhancing lesion. Also, the Phase 3 clinical trial data demonstrated that patients on KESIMPTA have a reduction in annualized relapse rate and MRI lesion activity compared to patients on teriflunomide

[Dr Williams]

And to that point, the ARR data and the MRI data show significant reductions for KESIMPTA vs teriflunomide. First, the ARR data demonstrated up to a 58% relative reduction, and then there was up to a 98% relative reduction in the number of Gadolinium-enhancing T1 lesions and up to an 85% relative reduction in the number of new or enlarging T2 lesions.In addition, I think the disability progression data are also impactful. Now, when I speak to my patients about KESIMPTA as a treatment option, I like to discuss these efficacy data with them. I stress that our goal is to decrease measures of RMS disease activity, and I tell my patients how the data from the ASCLEPIOS I and II clinical trials show how we might achieve that goal with KESIMPTA

[Dr Williams]

Beyond ASCLEPIOS I and II, we now have efficacy data up to 5 years with the ALITHIOS study. What are your key takeaways from the efficacy data in the extension study of KESIMPTA?

[Dr Smoot]

There's more and more evidence that shows patients taking KESIMPTA experienced reduced relapses, lesions, and disability progression compared to teriflunomide. In the extension study, the patients on KESIMPTA continued to have a reduced annualized relapse rate, with a 73% risk reduction in ARR for patients who switched from teriflunomide to KESIMPTA. Now, I should mention that no conclusions of statistical or clinical significance can be drawn because the open-label extension study was not blinded, not controlled, and included inherent self-selection bias for remaining in the trial

[Dr Williams]

I like what you pointed out. I'd also note that in the 5-year extension KESIMPTA showed a 97% risk reduction of gadolinium-enhancing T1 lesions and an 84% risk reduction in new or enlarging T2 lesions over time for patients who switched from teriflunomide to KESIMPTA. I now have a fair number of patients on KESIMPTA, and typically their MRIs are stable relative to their baseline MRI. Overall, the Phase 3 efficacy data and extension study align with what I'm seeing in my clinical practice

[Dr Williams]

So, we have the efficacy data, but how has Jane responded after switching to KESIMPTA?

[Dr Smoot]

She is very happy with making the transition to KESIMPTA. So far, she is doing well and hasn't had any relapses since making that change. I will of course continue to monitor her for signs of progression

[Dr Williams]

That's great to hear!

[Dr Smoot]

Yeah, it's always wonderful when our patients are doing well, and I'm glad we got to talk about efficacy, but any discussion on therapy wouldn't be complete unless we also talk about safety. So, what are your takeaways from the KESIMPTA Phase 3 safety data?

[Dr Williams]

I mean, I think the data are apparent, right? The safety profile for KESIMPTA is demonstrated and comparable to teriflunomide. For example, 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

[Dr Smoot]

Yeah, and the 5-year safety profile seems to be relatively consistent with the Phase 3 clinical trial data

[Dr Williams]

Agreed, and the proportion of patients with adverse events leading to discontinuation was 7.1%, and that's consistent with what was seen in the pivotal trials at 5.7%. Furthermore, there weren't any new safety signals identified in the extension study

[Dr Williams]

So, again, that's the data, but what about your patient? How has Jane tolerated KESIMPTA?

[Dr Smoot]

Initially, with the first couple injections, she had some mild flu-like symptoms and some muscle aching, but those have since resolved. And, you know, that is similar to what we would see in the clinical trials, so it wasn't that surprising

[Dr Williams]

Yeah, I've also had some patients who have more of a systemic response. They might have fever, headache, myalgia, chills, or fatigue with the first few administrations, but after that third injection, less than 3% of patients typically experience injection-related reactions

[Dr Williams]

So, we talked about how more than 80% of patients enrolled in KESIMPTA pivotal clinical trials were either treatment naïve or previously treated with one commonly used first-line DMT and how the data show that initiation of KESIMPTA results in a relative reduction of relapses. Additionally, KESIMPTA can be self-administered, so, all of that gives me confidence.

[Dr Williams]

What about you? What final thoughts would you like to share regarding early initiation of KESIMPTA in your MS patients?

[Dr Smoot]

I think the key thing to remember is we don't have any medications currently that help reverse MRI lesions. KESIMPTA reduces relapses, MRI lesion activity, and disability compared to teriflunomide. So, I feel better initiating a high efficacy therapy such as KESIMPTA from the very beginning

[Dr Williams]

Yeah, I agree. As I said, I am an advocate for using high efficacy therapy early to get patients on what I think will be an effective therapy for them as early as possible. I'd add that for any treatment plan it's important to ensure very close monitoring of the patient. If there's any worsening of disease activity, it should at least prompt a conversation about changing therapies, preferably as early as possible

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

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

Please see Important Safety Information throughout this presentation and accompanying full Prescribing Information, including Medication Guide