IgG in the long term
IgG in the long term
No decline in IgG was observed at the end of the Phase 3 ASCLEPIOS trials. Mean IgG levels remained stable for up to 6 years for KESIMPTA patients in the ALITHIOS extension analysis1,6,14
Demonstrated safety and tolerability profile of KESIMPTA® (ofatumumab)
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Pivotal Trial Safety
KESIMPTA has an established safety profile comparable to Aubagio® (teriflunomide), an oral therapy
Adverse events
Safety across pooled ASCLEPIOS I and II studies1
*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.
Rate of infections
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 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
Treatment-induced ADAs were detected in 2 of 914 (0.2%) KESIMPTA-treated patients; no patients with treatment-enhancing or neutralizing ADAs were identified1
Patients who took Aubagio in the trials received placebo injections. Over the trial period, systemic and local injection reactions were reported in 21% and 11% of patients treated with KESIMPTA compared to 15% and 6% of patients treated with Aubagio who received matching placebo injections, respectively1
Dig deeper into 6-year data
†As evidenced by ARR, MRI (Gd+ T1 and T2 lesions), and 3- and 6-month CDP. Primary end point, ARR reduction of 51% (0.11 vs 0.22), 58% (0.10 vs 0.25).1
Tolerability
Demonstrated tolerability profile: systemic injection-related reactions (IRR)
Systemic IRRs by injection in the ASCLEPIOS trials1-3
Injection-related reactions occurred in <3% of patients after the 3rd dose1
The incidence of injection-related reactions (systemic) was highest with the first injection (14.4%), decreasing with subsequent injections (4.4% with second, <3% with third injection)
Two (0.2%) patients treated with KESIMPTA reported serious injection-related reactions
The most frequently reported symptoms (≥2%) included fever, headache, myalgia, chills, and fatigue
Patients who took Aubagio in the trials received placebo injections. Over the trial period, systemic and local injection reactions were reported in 21% and 11% of patients treated with KESIMPTA compared to 15% and 6% of patients treated with Aubagio who received matching placebo injections, respectively
From injection 2 onward, the incidence of IRR was similar to placebo during the ASCLEPIOS trials1-3
Long-term Safety
Established safety profile demonstrated over 6 years6
No new safety signals were identified
The most common AEs were infections (COVID-19 [34.3%], nasopharyngitis [20.6%], upper respiratory tract infection [14.9%], and urinary tract infection [14.4%])
EAIRs for malignancies did not increase over time in the overall safety population‡
Incidence of serious infections remained stable over time and did not increase with KESIMPTA treatment up to 6 years
The most common serious infections were COVID-19 (1.4%), COVID-19 pneumonia (1.3%), and appendicitis (0.8%)
One case of serious opportunistic infection of Pneumocystis jirovecii was reported
ALITHIOS study design: ALITHIOS (N=1703) is an open-label, umbrella extension, Phase 3b, single-arm study evaluating long-term (up to 6 years) safety, tolerability, and effectiveness of KESIMPTA (20 mg SC) in subjects with RMS. The study enrolled 1367 RMS patients from the ASCLEPIOS I and II trials who continued KESIMPTA treatment. A long-term (up to 6 years) analysis (n=465) was conducted to evaluate efficacy in the recently diagnosed treatment-naïve subgroup treated with KESIMPTA. 366/465 (78.7%) of treatment-naïve patients were still receiving KESIMPTA at data cutoff (September 25, 2023). A long-term (up to 6 years) safety analysis was conducted to evaluate IgM/IgG levels and their association with serious infection. 1330/1703 (77.6%) of patients were still receiving KESIMPTA at data cutoff (September 25, 2023).6-9
No conclusions of clinical outcomes can be drawn.
*AEs related to decreased IgM levels are the most common reason for treatment discontinuation (n=64 [3.3%]).6
†Preferred terms for these 10 cases include: sudden death (n=1), completed suicide (n=1), COVID-19 and COVID-19 pneumonia (n=2), COVID-19 (n=2), intestinal metastasis (n=1), gastric ulcer perforation (n=1), pneumonia and septic shock (n=1), and pneumothorax and COVID-19 pneumonia (n=1).6
‡EAIR per 100 patient years is defined as the expected number of patients with the given event over 100 years of exposure to a treatment, assuming the event rate is constant over time. This is estimated by Poisson regression where participants' time is taken until first event occurrence or the last day the patient was at risk for those who did not have the event.6
AE, adverse event; EAIR, exposure-adjusted incidence rate per 100 patient years; SAE, serious adverse event.
*AEs related to decreased IgM levels are the most common reason for treatment discontinuation (n=64 [3.3%]).6
†Preferred terms for these 10 cases include: sudden death (n=1), completed suicide (n=1), COVID-19 and COVID-19 pneumonia (n=2), COVID-19 (n=2), intestinal metastasis (n=1), gastric ulcer perforation (n=1), pneumonia and septic shock (n=1), and pneumothorax and COVID-19 pneumonia (n=1).6
‡EAIR per 100 patient years is defined as the expected number of patients with the given event over 100 years of exposure to a treatment, assuming the event rate is constant over time. This is estimated by Poisson regression where participants' time is taken until first event occurrence or the last day the patient was at risk for those who did not have the event.6
AE, adverse event; EAIR, exposure-adjusted incidence rate per 100 patient years; SAE, serious adverse event.
KESIMPTA offers self-administration—at home or on the go1§
§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. If necessary, KESIMPTA may be stored at room temperature below 30°C (86°F) for up to 7 days and returned to the refrigerator, to be used within the next 7 days.1
Immune system Maintenance
A B-cell therapy that maintains long-term immune function
Patients on KESIMPTA maintained stable mean IgG levels for up to 6 years; mean IgM levels declined but remained above LLN6
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Mean IgG levels with KESIMPTA up to 6 years6
The majority of the participants had Ig levels above the LLN: 97.2% for IgG and 65.9% for IgM
No clinically meaningful association was observed between IgG/IgM levels <LLN and risk of serious infections
Serious, including life-threatening or fatal, bacterial, fungal, and new or reactivated viral infections have been observed during and following completion of treatment with anti-CD20 B-cell depleting therapies.
Mean IgM levels with KESIMPTA up to 6 years6
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 LLN6
*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.6
Read more on immunoglobulins
ALITHIOS study design: ALITHIOS (N=1703) is an open-label, umbrella extension, Phase 3b, single-arm study evaluating long-term (up to 6 years) safety, tolerability, and effectiveness of KESIMPTA (20 mg SC) in subjects with RMS. The study enrolled 1367 RMS patients from the ASCLEPIOS I and II trials who continued KESIMPTA treatment. A long-term (up to 6 years) analysis (n=465) was conducted to evaluate efficacy in the recently diagnosed treatment-naïve subgroup treated with KESIMPTA. 366/465 (78.7%) of treatment-naïve patients were still receiving KESIMPTA at data cutoff (September 25, 2023). A long-term (up to 6 years) safety analysis was conducted to evaluate IgM/IgG levels and their association with serious infection. 1330/1703 (77.6%) of patients were still receiving KESIMPTA at data cutoff (September 25, 2023).6-9
Components of immune function may be maintained in KESIMPTA patients
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T cells in the body
T cells in the body
Remained largely unaffected in KESIMPTA patients, as shown by data from a post hoc analysis of APLIOS, a 12-week, randomized open-label, parallel group. Phase 2 bioequivalence study conducted in 284 RMS patients from 41 study centers15
B cells in the spleen
B cells in the spleen
Preferential depletion of B cells in the lymph nodes is thought to be promoted by SC administration of KESIMPTA. KESIMPTA may spare B cells in the spleen, which may help maintain immune function, as suggested by preclinical evidence16,17
The precise mechanism by which KESIMPTA exerts its therapeutic effects is unknown. The clinical relevance of this data is unknown.
In the extension analysis (ALITHIOS), the overall incidence of serious infections was low6
Incidence of serious infections was consistent with that in the Phase 3 ASCLEPIOS I and II trials (EAIR: 1.55) and did not increase with treatment up to 6 years despite the COVID-19 pandemic
The most common serious infections were COVID-19 (1.4%), COVID-19 pneumonia (1.3%), and appendicitis (0.8%)
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.
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
Learn more on adherence and persistence from your peers
No increased risk of severe or serious COVID-19 outcomes in patients taking KESIMPTA over 5 years in the ALITHIOS trial18†
COVID-19 related data—Analysis of data from December 2019 to September 25, 2022
648 (38%) of the 1703 patients (as of September 25, 2022) enrolled in ALITHIOS who received KESIMPTA reported that they had contracted COVID-19
COVID-19 cases with severity, seriousness, outcomes, vaccination status, and breakthrough infections were all included in this analysis
The open-label extension study is not blinded and not controlled
50 cases were considered serious with 82% recovery rate at the cutoff; there were 5 fatal outcomes
Fatal outcomes (5/648 or 0.8%) due to COVID-19 in KESIMPTA-treated patients were lower than those reported in the general population (2.1%)19
Three of these patients were unvaccinated; 2 patients were fully vaccinated‡
The 5 fatal cases consisted of the following: COVID-19 (n=2), COVID-19 pneumonia (n=1), COVID-19 and COVID-19 pneumonia (n=1), COVID-19 pneumonia and pneumothorax (n=1)
No statistical or clinical conclusion can be made.
†Results from an analysis of data from the open-label, long-term extension Phase 3b study (ALITHIOS) from the start of the COVID-19 pandemic in December 2019 to September 25, 2022. As of September 25, 2022, 648 of the 1703 patients enrolled in ALITHIOS who received KESIMPTA reported that they had contracted COVID-19 (confirmed [n=603]; suspected [n=45]).18,19
‡Fully vaccinated means at least 14 days after completing the primary vaccine series, may or may not be after booster. These 2 fatal cases occurred before booster: one case had multiple risk factors for severe COVID-19 and the other case was complicated by a bilateral pneumothorax.18
Learn more about KESIMPTA and Vaccines
ADA, anti-drug antibody; BL, baseline; Ig, immunoglobulin; IgG, immunoglobulin G; IgM, immunoglobulin M; LLN, lower limit of normal; RMS, relapsing multiple sclerosis; SC, subcutaneous; SE, standard error.
References: 1. Kesimpta. Prescribing information. Novartis Pharmaceuticals Corp. 2. Data on file. OMB157G (ofatumumab). Summary of clinical efficacy in relapsing multiple sclerosis. Novartis Pharmaceuticals Corp; East Hanover, NJ. December 2019. 3. Hauser SL, Bar-Or A, Cohen JA, et al; ASCLEPIOS I and ASCLEPIOS II trial groups. Ofatumumab versus teriflunomide in multiple sclerosis. Supplemental appendix. N Engl J Med. 2020;383(6):546-557. 4. Hauser SL, Bar-Or A, Cohen JA, et al. ASCLEPIOS I and ASCLEPIOS II trial groups. Ofatumumab versus teriflunomide in multiple sclerosis. 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. P0409. Presented at: 8th Joint ACTRIMS-ECTRIMS Meeting MS; September 11-13, 2020; Virtual. 6. Wiendl H, Hauser SL, Nicholas J, et al. Longer-term safety and efficacy of ofatumumab in people with relapsing multiple sclerosis for up to 6 years. P9.010. Presented at: 76th American Academy of Neurology Annual Meeting; April 13-18, 2024; Denver, CO. 7. 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. 2022;28(10):1576-1590. 8. Pardo G, Hauser SL, Bar-Or A, et al. Longer-term (up to 6 years) efficacy of ofatumumab in people with recently diagnosed and treatment-naive relapsing multiple sclerosis. S31.003. Presented at: 76th American Academy of Neurology Annual Meeting; April 13-18, 2024; Denver, CO. 9. Data on file. OMB157 (ofatumumab). Patient Population at 6 Years. Novartis Pharmaceuticals Corp; East Hanover, NJ. August 2024. 10. Data on file. Serious Infections in Patients with IgG ≤LLN. Novartis Pharmaceuticals; East Hanover, NJ. April 2024. 11. 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. 12. Delves PJ. Molecular components of the immune system. Merck Manual. Updated September 2022. Accessed January 18, 2023. 13. Mayo Clinic Laboratories. Immunoglobulins (IgG, IgA, and IgM), serum. Accessed November 3, 2023. https://neurology.testcatalog.org/show/IMMG 14. Hauser SL, Cross AH, Winthrop K, et al. Long-term safety of ofatumumab in patients with relapsing multiple sclerosis. S14.004. Presented at: the American Academy of Neurology; April 2-7, 2022; Seattle, WA. 15. 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. Presented at: 6th Congress of the European Academy of Neurology; May 23-26, 2020; Paris, France; Virtual. 16. 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. Presented at: 71st American Academy of Neurology Annual Meeting; May 4-10, 2019; Philadelphia, PA. 17. 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;10:1340. doi:10.3389/fimmu.2019.01340 18. Cohen JA, Hauser SL, Cross AH, et al. Five-year safety of ofatumumab in people living with relapsing multiple sclerosis. P8.2-004. Presented at: 75th American Academy of Neurology Annual Meeting; April 22-27, 2023; Boston, MA. 19. Cross AH, Delgado S, Habek M, et al. COVID-19 outcomes and vaccination in people with relapsing multiple sclerosis treated with ofatumumab. Neurol Ther. 2022;11:741-758. doi:10.1007/s40120-022-00341-z