Empowering a targeted and precisely delivered treatment selection in people living with RMS
Thirty years ago, patients with multiple sclerosis (MS) faced a steep uphill battle choosing from a narrow selection of treatment options that tended to make minimal impact on the course of their disease. Since then, the U.S. Food and Drug Administration (FDA) has approved more than 20 new disease modifying therapies (DMTs) to alter the MS disease course and help treat relapses.1
The boom in treatment innovation has led to significant improvements in the lives of people living with MS and a shift in the conversation between patients and treating physicians, as the focus now is to initiate RMS therapy as early as possible.2 However, high efficacy, favorable safety and the patient’s routine remain important considerations for neurologists and patients as they discuss treatment options and come to a shared decision together. “Physicians now have the ability to select a treatment best suited for the individual patient,” says Ann Bass, MD, Director of the Neurology Center of San Antonio, Texas. “The primary goal is to find the treatment for our patients immediately following their MS diagnosis.”
Ann Bass, MD, Director of the Neurology Center of San Antonio, Texas
The current decade brings additional treatment options for people living with MS. Kesimpta® (ofatumumab) 20 mg injection was approved by the FDA in August 2020 for subcutaneous use for the treatment of relapsing forms of MS (RMS), including clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease in adults.3 As the first and only self-administered, subcutaneous targeted B-cell therapy for people living with RMS, Kesimpta provides a RMS treatment with powerful efficacy, a favorable safety profile and flexibility for patients which can be taken one minute a month when the patient is ready to administer.3*†
Efficacy Is a Priority
Neurologists know all too well that timing is critical to the management of early RMS and with patients turning to their healthcare providers to guide them through this decision process, treating physicians need to evaluate the unique characteristics of each potential treatment. “For me, a top priority for an early RMS patient is to examine the efficacy of a treatment on parameters such as relapse rate or MRI activity, delaying disability and composite measures like no evidence of disease activity,” says Dr. Bass. “Superior efficacy on reducing relapses or lesion activity is one of the key differentiating factors for me when looking at some of the other efficacious treatments out there.”
In the pivotal ASCLEPIOS trials, Kesimpta demonstrated powerful efficacy across several key endpoints, including a significant reduction in the annualized relapse rate (ARR) by 51% (0.11 vs 0.22) and 59% (0.10 vs 0.25) compared to teriflunomide (P<.001 in both studies), respectively. Kesimpta also demonstrated significant reductions in the number of gadolinium-enhancing (Gd+) T1 and new or enlarging T2 lesions, and relative risk of 3-month confirmed disability progression (CDP).
Assessing the Safety Profile
Efficacy is only part of the conversation – safety is also a critical discussion point for both patients and physicians. According to Dr. Bass, a common concern with high-efficacy therapies is safety.
In the Phase 3 ASCLEPIOS trials, Kesimpta demonstrated an overall safety profile similar to teriflunomide, a commonly prescribed, first-line oral treatment for early RMS patients.3 Upper respiratory tract infection, headache, injection-related reactions, and local injection site reactions were the most commonly observed adverse reactions with Kesimpta (incidence greater than 10%). The overall rate of infections and serious infections in patients treated with Kesimpta was similar to patients who were treated with teriflunomide (51.6% vs 52.7%, and 2.5% vs 1.8%, respectively).3 Kesimpta has the potential for an increased risk of infections, including serious bacterial, fungal, and new or reactivated viral infections; some of these infections have been fatal in patients treated with other anti-CD20 antibodies.3
In addition to adverse events, immunoglobulin (Ig) levels can be a critical indicator in the safety profile of a B-cell therapy, as lower serum Ig levels have been linked to an increased risk of infection in RMS patients.4 When selecting a B-cell therapy, it’s important to consider efficacy data, as well as the safety profile, including long-term data on immunoglobulin G (IgG) levels and the associated risk of serious infections.
In the ASCLEPIOS trials, no decline in IgG was observed at the end of the study and 14.3% patients treated with Kesimpta experienced a decrease in immunoglobulin M (IgM).5 In the ALITHIOS trial – an ongoing open-label, umbrella extension Phase 3b, single-arm, multi-center study evaluating long-term (up to 5 years) safety, tolerability, and effectiveness of Kesimpta in patients with RMS‡ – mean IgG levels remained stable over 3.5 years; mean IgM levels declined over time but remained above the lower limit of normal (LLN) for up to 3.5 years in people continuously treated with Kesimpta and those who switched from teriflunomide.5 Additionally, no increased risk of serious infection associated with a change in IgG/IgM levels was observed at 3.5 years.5 Ig testing and monitoring can help manage increased risk of serious infection.5
While efficacy and safety remain cornerstones in navigating treatment selection, flexibility in administration can be a considerable factor for many people living with RMS. Dr. Bass works with patients to better understand what route of administration would be best suited for their lifestyle. She may ask questions like, “Do they have young children that need more of their time?,” “Do they have an active lifestyle or profession?,” “Do they have access to an infusion center?,” or “Do they feel confident in their ability to take a daily treatment?”. According to Dr. Bass, “For patients who have an active lifestyle or family or are less accepting of their diagnosis or less informed, a treatment’s route of administration and flexibility are higher on my priority list to help them navigate through the more than 20 RMS treatment options.”
Traditionally, B-cell treatments, which bind to and deplete B-cells, have predominantly been available in hospitals or infusion treatment centers, which may add costs to the healthcare system.6,7 As the fastest growing RMS DMT in the United States with more than 1,800 prescribers and 5,000 patients and counting,8,§ Kesimpta is a high-efficacy B-cell therapy with a favorable safety profile that provides patients the flexibility of self-administration from anywhere one minute a month when the patient is ready to administer,*† which may reduce the need to travel to an infusion center.3,9 The ability to be treated at home is especially important to many patients during the COVID-19 global pandemic, when they may be hesitant to seek medical care outside the home.‖¶
The Future of MS Treatments
While there is no cookie cutter approach to specific treatment algorithms physicians and patients use to select an MS treatment, Dr. Bass is optimistic and excited for where the field is headed. “We’re getting to a point where we may be able to select treatments that are more specific to each patient,” says Dr. Bass. When it comes to the ideal Kesimpta patient profile, there isn’t a singular descriptor. “The development of specifically designed therapies like Kesimpta is giving us the opportunity to tailor our treatment.”
According to Dr. Bass, the future looks bright for people living with MS. If you visit her clinic, her patients today tend to be younger and earlier in their disease journey and diagnosis when they first seek care compared to 25 years ago. This trend of patients living with MS getting diagnosed and started on treatments earlier represents real advances in the treatment and care of the disease, says Dr. Bass. “The prognosis looks better and better with subsequent generations. I look around my waiting room now and see fewer patients in walkers and wheelchairs, and that is really exciting.”
For more information on Kesimpta, please visit https://www.hcp.novartis.com/products/kesimpta/rms/.
*As per stability technical specification data, when the patient is ready to inject, it typically takes less than 1 minute a month to administer. Initial dosing period consists of 20 mg subcutaneous doses at weeks 0, 1, and 2. Subsequent once monthly dosing. Please see Instructions for Use for more detailed instructions on preparation and administration of Kesimpta.
†This compares administration time of the infusion or injection. It does not reflect the total time required for each treatment, which includes pre- and post-administration time.
‡The study enrolled 1703 RMS patients from the APLIOS, APOLITOS, and ASCLEPIOS I and II trials who continued Kesimpta treatment. A long-term safety analysis from ALITHIOS was conducted to evaluate IgM/IgG levels and their association with serious infection for up to 3.5 years.
§Based on IQVIA Rx volume as through July 30, 2021
‖The initial dosing period consists of 20 mg SC doses at Weeks 0, 1, and 2.
¶Kesimpta Sensoready Pens must be refrigerated at 2°C to 8°C (36°F to 46°F). Keep product in the original carton to protect from light until the time of use. Do not freeze. To avoid foaming, do not shake.
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.
IMPORTANT SAFETY INFORMATION
Contraindication: KESIMPTA is contraindicated in patients with active hepatitis B virus infection.
Warnings and Precautions
Infections: An increased risk of infections has been observed with other anti-CD20 B-cell depleting therapies. KESIMPTA has the potential for an increased risk of infections including serious bacterial, fungal, and new or reactivated viral infections; some have been fatal in patients treated with other anti-CD20 antibodies. The overall rate of infections and serious infections in KESIMPTA-treated patients was similar to teriflunomide-treated patients (51.6% vs 52.7%, and 2.5% vs 1.8%, respectively). The most common infections reported by KESIMPTA-treated patients in relapsing MS (RMS) trials included upper respiratory tract infection (39%) and urinary tract infection (10%). Delay KESIMPTA administration in patients with an active infection until resolved.
Consider the potential increased immunosuppressive effects when initiating KESIMPTA after an immunosuppressive therapy or initiating an immunosuppressive therapy after KESIMPTA.
Hepatitis B Virus: Reactivation: No reports of hepatitis B virus (HBV) reactivation in patients with MS treated with KESIMPTA. However, HBV reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, has occurred in patients treated with ofatumumab at higher intravenous doses for chronic lymphocytic leukemia (CLL) than the recommended dose in MS and in patients treated with other anti-CD20 antibodies.
Infection: KESIMPTA is contraindicated in patients with active hepatitis B disease. Fatal infections caused by HBV in patients who have not been previously infected have occurred in patients treated with ofatumumab at higher intravenous doses for CLL than the recommended dose in MS. Perform HBV screening in all patients before initiation of KESIMPTA. Patients who are negative for HBsAg and positive for HB core antibody [HBcAb+] or are carriers of HBV [HBsAg+], should consult liver disease experts before starting and during KESIMPTA treatment.
Progressive Multifocal Leukoencephalopathy: No cases of progressive multifocal leukoencephalopathy (PML) have been reported for KESIMPTA in RMS clinical studies; however, PML resulting in death has occurred in patients being treated with ofatumumab at higher intravenous doses for CLL than the recommended dose in MS. In addition, JC virus infection resulting in PML has also been observed in patients treated with other anti-CD20 antibodies and other MS therapies. If PML is suspected, withhold KESIMPTA and perform an appropriate diagnostic evaluation. If PML is confirmed, KESIMPTA should be discontinued.
Vaccinations: Administer all immunizations according to immunization guidelines: for live or live-attenuated vaccines at least 4 weeks and, whenever possible at least 2 weeks prior to starting KESIMPTA for inactivated vaccines. The safety of immunization with live or live-attenuated vaccines following KESIMPTA therapy has not been studied. Vaccination with live or live-attenuated vaccines is not recommended during treatment and after discontinuation until B-cell repletion.
Vaccination of Infants Born to Mothers Treated with KESIMPTA During Pregnancy. For infants whose mother was treated with KESIMPTA during pregnancy, assess B-cell counts prior to administration of live or live-attenuated vaccines. If the B-cell count has not recovered in the infant, do not administer the vaccine as having depleted B-cells may pose an increased risk in these infants.
Injection-Related Reactions: Injection-related reactions with systemic symptoms occurred most commonly within 24 hours of the first injection, but were also observed with later injections. There were no life-threatening injection reactions in RMS clinical studies.
The first injection of KESIMPTA should be performed under the guidance of an appropriately trained health care professional. If injection-related reactions occur, symptomatic treatment is recommended.
Reduction in Immunoglobulins: As expected with any B-cell depleting therapy, decreased immunoglobulin levels were observed. Monitor the levels of quantitative serum immunoglobulins during treatment, especially in patients with opportunistic or recurrent infections and after discontinuation of therapy until B-cell repletion. Consider discontinuing KESIMPTA therapy if a patient with low immunoglobulins develops a serious opportunistic infection or recurrent infections, or if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins.
Fetal Risk: Based on animal data, KESIMPTA can cause fetal harm due to B-cell lymphopenia and reduce antibody response in offspring exposed to KESIMPTA in utero. Transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 B-cell depleting antibodies during pregnancy. Advise females of reproductive potential to use effective contraception while receiving KESIMPTA and for at least 6 months after the last dose.
Most common adverse reactions (>10%) are upper respiratory tract infection, headache, injection-related reactions, and local injection-site reactions.
Please see full Prescribing Information, including Medication Guide.
Dr. Bass is a consultant for Novartis.
- Olek MJ. Multiple sclerosis. Annals of internal medicine. 2021;174(6):ITC81-ITC96.
- Stankiewicz JM, Weiner HL. An argument for broad use of high efficacy treatments in early multiple sclerosis. Neurology-Neuroimmunology Neuroinflammation. 2020;7(1):1-7.
- Kesimpta Prescribing Information. East Hanover, NJ: Novartis Pharmaceuticals Corp; August 2020.
- Derfuss T, Weber MS, Hughes R, et al. Serum immunoglobulin levels and risk of serious infections in the pivotal phase III trials of ocrelizumab in multiple sclerosis and their open label extensions [OPR-65]. Presented at: 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); 11-13 September 2019; Stockholm, Sweden.
- Jasinska E, Habek M, Wynn D, et al. Impact of ofatumumab on immune responses post-vaccination in RMS patients: ALITHIOS vaccination sub-study design [OPR-207]. Presented at: 7th Congress of the European Academy of Neurology; 19-22 June, 2021; Virtual.
- Lehmann-Horn K, Kronsbein HC, Weber MS. Targeting B cells in the treatment of multiple sclerosis: recent advances and remaining challenges. Ther Adv Neurol Disord. 2013;6(3):161-173.
- Dieguez G, Engel T, Jacobson N. Site of service and cost dispersion of infused drugs. Accessed October 14, 2021. https://www.milliman.com/insight/2019/Site-of-Service-and-Cost-Dispersion-of-Infused-Drugs/
- Data on file. Novartis Pharmaceuticals Corp; 2020.
- Bar-Or A, Fox E, Goodyear A, et al. Onset of B-cell Depletion with Subcutaneous Administration of Ofatumumab in Relapsing Multiple Sclerosis: Results from the APLIOS Bioequivalence Study. Poster presentation at: ACTRIMS; February 2020; West Palm Beach, FL.
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