SAFETY AND TOLERABILITY
Demonstrated safety profile
Dr Patricia Coyle reviews the safety profile for KESIMPTA
More than
of patients enrolled in KESIMPTA® pivotal clinical trials were either treatment-naïve or previously treated with commonly used first-line therapies like interferon and dimethyl fumarate.5,6
Adverse reactions
Safety across pooled
ASCLEPIOS I and II studies1
Adverse reactions in patients with RMS with an incidence of at least 5% with KESIMPTA and a greater incidence than Aubagio® (teriflunomide).
*Includes the following: nasopharyngitis, upper respiratory tract infection, influenza, sinusitis, pharyngitis, rhinitis, viral upper respiratory infection, tonsillitis, acute sinusitis, pharyngotonsillitis, laryngitis, pharyngitis streptococcal, viral rhinitis, sinusitis bacterial, tonsillitis bacterial, viral pharyngitis, viral tonsillitis, chronic sinusitis, nasal herpes, tracheitis.
KESIMPTA and Infection
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The overall rate of infections and serious infections in patients treated with KESIMPTA was similar to Aubagio (51.6% vs 52.7%, and 2.5% vs 1.8%, respectively)1
Treatment Discontinuations
Pooled data from ASCLEPIOS I and II studies
-
Pooled data from both clinical trials show that treatment discontinuation rates due to adverse reactions were similar between KESIMPTA (5.7%) and Aubagio (5.2%)2
-
The most common cause of discontinuation in patients treated with KESIMPTA was low IgM (3.3%), defined in trial protocols as IgM at 10% below the LLN1
Give your patients confidence with evidence on long-term safety with KESIMPTA.
3.5 year safety profile3
AEs occurring in ≥5% of the long-term safety population at 3.5 years
Patients with ≥1 event, n (%)
Overall safety population
(N=1969)
Continuous KESIMPTA group
(N=1292)
Injection-related reactions
Injection-related systemic reaction
489 (24.8)
336 (26.0)
Injection-site reaction
227 (11.5)
171 (13.2)
Infections
All
infections
reported as AEs
1070 (54.3)
761 (58.9)
Nasopharyngitis
Nasopha-
ryngitis
331 (16.8)
257 (19.9)
Upper respiratory tract infection
203 (10.3)
148 (11.5)
Urinary tract infection
192 (9.8)
156 (12.1)
COVID-19†
114 (5.8)
70 (5.4)
Other AEs
Headache
238 (12.1)
197 (15.2)
IgM decreased
215 (10.9)
153 (11.8)
Back pain
161 (8.2)
135 (10.4)
Fatigue
135 (6.9)
112 (8.7)
Arthralgia
133 (6.8)
102 (7.9)
Diarrhea
108 (5.5)
94 (7.3)
†Incidence of "COVID-19" refers to confirmed SARS-CoV-2 infections, and "COVID-19 pneumonia" refers to cases of COVID-19 pneumonia as reported by the investigator. Investigators may report an AE both as "COVID-19" and "COVID-19 pneumonia."
-
The nature and frequency of the most common AEs were comparable with those reported in ASCLEPIOS I and II3
-
In the overall population, the proportion of patients with AEs leading to discontinuation (5.8%) was consistent with those observed in the pivotal trials (5.7%) with KESIMPTA2,3
-
Serious infections occurred in less than 3% of the overall safety population3
-
No opportunistic infections or progressive multifocal leukoencephalopathy (PML) events were reported, and the risk of malignancies did not increase3
-
Two deaths were reported, both in the continuous KESIMPTA group, and neither were reported as related to KESIMPTA3
Study design: ALITHIOS, an ongoing open-label, umbrella extension Phase 3b, single-arm, multicenter study evaluating long-term (up to 5 years) safety, tolerability, and effectiveness of KESIMPTA (20 mg SC) in subjects with RMS. The study enrolled 1703 RMS patients from the APLIOS, APOLITOS, and ASCLEPIOS I and II trials who continued KESIMPTA treatment. An interim analysis of this study provides up to 3.5 years of cumulative safety data, from initiation of KESIMPTA treatment in the core/extension studies to the cut-off date of January 29, 2021.3
No conclusions of clinical outcomes can be drawn.
Demonstrated tolerability profile: injection-related reactions (systemic)
Injection-related reactions (systemic), by injection4
Injection-related reactions
(systemic), by injection4
-
Injection-related reactions were mostly (99.8%) mild to moderate in severity. Two (0.2%) KESIMPTA-treated RMS patients reported serious injection-related reactions1
-
The incidence of injection-related reactions (systemic) was highest with the first injection (14.4%), decreasing with subsequent injections (4.4% with second, <3% from third injection)1
-
Injection-related reactions (systemic) and injection-site reactions (local) were reported in 21% and 11% of patients treated with KESIMPTA, respectively, compared to 15% and 6% in the Aubagio-treated patients1
-
The most frequently reported symptoms (≥2%) included fever, headache, myalgia, chills, and fatigue1
No conclusions of clinical outcomes can be drawn.
Give your patients the comfort of
knowing what to expect with
potential injection-related
reactions with KESIMPTA.
Walt: husband, dad, aeronautical engineer, KESIMPTA patient†
†Actual KESIMPTA patient who was compensated for their time. Individual results may vary.
KESIMPTA and components of immune function
Components of immune function may be maintained in KESIMPTA patients
IgG long term
T cells in the body
B cells in the spleen
IgG is created by B cells to work against specific antigens7
T cells help B cells produce antibodies and orchestrate the immune system response8
B cells serve as antigen-presenting cells that activate T cells in the periphery9
-
In the Phase 3 ASCLEPIOS trials, no decline in IgG was observed at the end of the study1
-
In the extension analysis, mean IgG levels remained stable for up to 3.5 years in patients taking KESIMPTA, based on an analysis of ALITHIOS3
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Data from a post hoc analysis of APLIOS, a 12-week, randomized open-label, multicenter, parallel group Phase 2 bioequivalence study conducted in 284 RMS patients from 41 study centers, showed that T cells remained largely unaffected in KESIMPTA patients12
-
SC administration of KESIMPTA is thought to promote preferential depletion of B cells in the lymph nodes10
-
Preclinical evidence suggests that KESIMPTA may spare B cells in the spleen, which may help maintain immune function11
Phase 3 studies and post hoc analysis
Phase 2 post hoc analysis
Preclinical data
The precise mechanism by which KESIMPTA exerts its therapeutic effects is unknown. The clinical relevance of this data is unknown.
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.3
Immunoglobulins and RMS
Serum immunoglobulin (Ig) levels can be predictors of infection risk when selecting B-cell therapy for RMS patients
-
Immunoglobulins play a critical role in immune response by working to destroy pathogens, including bacteria and viruses
Immunoglobulin M
![]()
The immune system's primary response
to infection. Approximately 5% of
antibodies in blood serum are IgM13,14Immunoglobulin G
![]()
Protects the body from infection.
Approximately 70% of antibodies in
blood serum are IgG13 -
B-cell treatment may lead to Ig decline in RMS patients, which may increase infection risk1,13,15
In the extension analysis
Patients on KESIMPTA maintained stable mean IgG levels for up to
3.5 years; mean IgM levels
declined but remained above LLN3‡
KESIMPTA IgG/IgM data
-
In the Phase 3 ASCLEPIOS trials, no decline in IgG was observed at the end of the study1
-
In the extension analysis, mean IgG levels remained stable for up to 3.5 years in patients taking KESIMPTA3
IgG levels with KESIMPTA over 3.5 years3
IgG levels with KESIMPTA over
3.5 years3
Average IgG levels remained within the reference range (patients aged >18 years): 5.65-17.65 g/L.16
-
In the Phase 3 ASCLEPIOS trials, 14.3% of patients treated with KESIMPTA experienced a decrease in IgM1
-
In the long-term analysis, mean IgM declined over time but remained above the LLN for up to 3.5 years3
IgM levels with KESIMPTA over 3.5 years3
IgM levels with KESIMPTA
over 3.5 years3
Average IgM levels remained within the reference range (patients aged >18 years): 0.4-2.3 g/L.16
‡For all pooled analyses, a fixed value of LLN (using ALITHIOS study
reference) was used: IgG: 5.65 g/L/IgM: 0.4 g/L.
§Switching period refers to the patients started with Aubagio and not applicable to the patients treated
with KESIMPTA in the core period; for Aubagio/KESIMPTA group data from first dose of Aubagio until last
dose of KESIMPTA plus 100 days/analyses cutoff dates have been used.
KESIMPTA and serious infection
In an extension study analysis, no increased risk of serious infection associated with change in IgG/IgM levels was observed at 3.5 years3
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 CD-20 antibodies.1
Patients with at least 1 serious infection within 1 month prior and until 1 month after any
series of drops in IgM/IgG <LLN3
Patients with at least 1 serious infection within 1
month prior and until 1 month after any series of
drops in IgM/IgG <LLN33
Patients with at least 1 serious
infection within 1 month prior and
until 1 month after any series of
drops in IgM/IgG <LLN33
-
The overall incidence of serious infections in KESIMPTA-treated patients was low for up to 3.5 years3§
*Number of patients with IgM/IgG <LLN at least once at any time during the post-baseline visits.
†Number of patients with no occurrence of IgM/IgG <LLN at least once at any time during the post-baseline visit.
‡IR per 100 PY estimated via a Poisson regression model with only treatment as the factor and with the log-link and natural logarithm of time as the offset variable. For all pooled analyses, a fixed value of LLN (using ALITHIOS study reference) was used: IgM: 0.4 g/L; and IgG: 5.65 g/L.
§Low incidence of serious infection defined as 1.39 incidence rate per 100 PY.
Ig testing and monitoring can help manage increased risk of serious infection
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Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with KESIMPTA until B-cell repletion
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Consider discontinuing KESIMPTA if a patient develops a serious opportunistic infection or recurrent infections if immunoglobulin levels indicate immune compromise
Consider efficacy. Consider safety.
Consider 3.5 years of Ig data.
Start patients on KESIMPTA today
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Submit a Start Form by fax or online at CoverMyMeds®
VISIT COVERMYMEDS®AE=adverse event; BL=baseline; Ig=immunoglobulin; IgG=immunoglobulin G; IgM=immunoglobulin M; IR=incidence rate; LLN=lower limit of normal; MOA=mechanism of action; PT=preferred term; PY=patient-years; RMS=relapsing multiple sclerosis; SC=subcutaneous; SE=standard error; URTI=upper respiratory tract infection; UTI=urinary tract infection.
References: 1. Kesimpta [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp.
2. Data on file. OMB157G (ofatumumab). Summary of clinical safety. Novartis Pharmaceuticals Corp; East Hanover, NJ. January 2020.
3. Hauser SL, Cross AH, Winthrop K, et al. Safety experience with continued exposure to ofatumumab in patients with relapsing forms of multiple sclerosis for up to 3.5 years. Mult Scler J. 2022;1-15. doi:10.1177/13524585221079731
4. Hauser SL, Bar-Or A, Cohen JA, et al; for the ASCLEPIOS I and ASCLEPIOS II trial groups. Ofatumumab versus teriflunomide in multiple sclerosis [supplemental appendix]. N Engl J Med. 2020;383(6):546-557.
5. Conway D, Hersh C, Wang M, Yang F, Deshpande C. Treatment failure in patients with multiple sclerosis initiating frequently used first line therapies. PO02. Poster presented at: 8th Joint ACTRIMS-ECTRIMS Meeting MS; September 11-13, 2020; Virtual.
6. Hauser SL, Bar-Or A, Cohen JA, et al; for the ASCLEPIOS I and ASCLEPIOS II trial groups. Ofatumumab versus teriflunomide in multiple sclerosis. N Engl J Med. 2020;383(6):546-557.
7. Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001.
8. Vabret N, Britton GJ, Gruber C, et al. Immunology of COVID-19: current state of the science. Immunity. 2020;52(6):910-941. doi:10.1016j.immuni.2020.05.002
9. Häusser-Kinzel S, Weber MS. The role of B cells and antibodies in multiple sclerosis, neuromyelitis optica, and related disorders. Front Immunol. 2019;10:201. doi:10.3389/fimmu.2019.002021
10. Torres JB, Roodselaar J, Sealey M, et al. Distribution and efficacy of ofatumumab and ocrelizumab in humanized-CD20 mice following subcutaneous or intravenous administration. P2.2-052. Poster presented at: 71st American Academy of Neurology Annual Meeting; May 4-10, 2019; Philadelphia, PA.
11. Theil D, Smith P, Huck C, et al. Imaging mass cytometry and single-cell genomics reveal differential depletion and repletion of B-cell populations following ofatumumab treatment in cynomolgus monkeys. Front lmmunol. 2019;10:1-11.
12. Wiendl H, Fox E, Goodyear A, et al. Effect of subcutaneous ofatumumab on lymphocyte subsets in patients with RMS: analysis from the APLIOS study. LB129. Poster presented at: 6th Congress of the European Academy of Neurology; May 23-26, 2020; Paris, France; Virtual.
13. Immunoglobulins (IgA, IgG, IgM)—What's being tested? Merck Manual. Accessed February 10, 2022. https://www.merckmanuals.com/-/media/Manual/LabTests/
ImmunoglobulinsIgAIgGIgM
14. Mayo Clinic Laboratories. Immunoglobulins (IgG, IgA, and IgM), serum. Accessed February 10, 2022. https://neurology.testcatalog.org/show/IMMG
15. 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); September 11-13, 2019; Stockholm, Sweden.
16. Data on file. Novartis Pharmaceuticals Corp; East Hanover, NJ. August 2021.