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).

Chart showing Kesimpta favorable safety profile compared to 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

  • 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 profile

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

Chart showing Kesimpta injection-related reactions (systemic), by injection. Image shows injection-related reactions were reported in less than 3 percent of patients after the 3rd dose.
  • 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.

'Before I started therapy, it was important for me to be comfortable with the risks.'- Walt: dad, husband, aeronautical engineer, Kesimpta patient.

Before I started therapy, it was important for me to be aware of the potential risks.

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

This chart shows that Kesimpta may preserve components of immune function in your patients.

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 is the immune system's primary response to infection and immunoglobin G is the most prevalent antibody that protects the body from infection.
  • 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

This chart shows IgG levels with Kesimpta over 3.5 years.

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

This chart shows IgM levels with Kesimpta over 3.5 years.

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

This chart shows patients with at least 1 serious infection within 1 month prior and until 1 month after any series of drops in IgM/IgG <LLN.
  • The overall incidence of serious infections in KESIMPTA-treated patients was low for up to 3.5 years

*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

  • 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

Consider efficacy. Consider safety.
Consider 3.5 years of Ig data.

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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; 2020. 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.

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

INDICATION

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.

SEE IMPORTANT SAFETY INFORMATION

INDICATION

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.

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