SAFETY AND TOLERABILITY
Demonstrated safety profile
Dr. Patricia Coyle reviews the safety profile for KESIMPTA® (ofatumumab)
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.1,2
Adverse reactions
Safety across pooled ASCLEPIOS I and II studies3
≥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.
Rate of 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)3
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%)4
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 LLN3
Treatment-induced anti-drug antibodies (ADAs) were detected in 2 of 914 (0.2%) KESIMPTA-treated patients; no patients with treatment-enhancing or neutralizing ADAs were identified.3
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.3
Give your patients confidence with evidence on long-term safety with KESIMPTA
KESIMPTA has an established safety profile demonstrated over 5 years5
No new safety signals were identified
The most common AEs were infections (COVID-19 [30.3%], nasopharyngitis [19%], URTI [12.8%], and UTI [12.7%]). Most (90.3%) infections resolved without discontinuing KESIMPTA treatment
The nature and frequency of the most common AEs were comparable with those reported in ASCLEPIOS I and II6
In the overall population, the proportion of patients with AEs leading to discontinuation (7.1%) was consistent with those observed in the pivotal trials (5.7%) with KESIMPTA
Serious infections occurred in 5.38% of the overall safety population over 5 years
EAIRs for malignancies did not increase over time in the overall KESIMPTA population‡
ALITHIOS study design: ALITHIOS (N=1703) was an open-label, umbrella extension, Phase 3b, single-arm study evaluating long-term (up to 5 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. Of these, 1145 patients were still receiving KESIMPTA at 5 years. A long-term safety analysis was conducted to evaluate IgM/IgG levels and their association with serious infection. 1416 patients were still receiving KESIMPTA at 5 years.5-9
AE, adverse event; EAIR, exposure-adjusted incidence rate per 100 patient years; PT, preferred term; SAE, serious adverse event; URTI, upper respiratory tract infection; UTI, urinary tract infection.
No conclusions of clinical outcomes can be drawn.
*AEs related to reduced IgM levels is the most common reason for treatment discontinuation (n=71 [3.6%]).
†PT for these 9 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), pneumonia and septic shock (n=1), and pneumothorax (n=1).
‡EAIRs per 100 patient years are defined as the number of patients with a particular event during 100 years of exposure to a treatment, estimated by Poisson regression in which patients were censored at time of first event.
Demonstrated tolerability profile: injection-related reactions (systemic)3,4,10
Injection-related reactions (systemic), by injection in the ASCLEPIOS trials
Injection-related reactions occurred in
<3% of patients after the 3rd dose
Injection-related reactions were mostly (99.8%) mild to moderate in severity. Two (0.2%) KESIMPTA-treated relapsing MS patients reported serious injection-related reactions3
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)3
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 patients3
The most frequently reported symptoms (≥2%) included fever, headache, myalgia, chills, and fatigue3
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 aware of the potential risks."
Walt: husband, dad, aeronautical engineer, KESIMPTA patient
Real patient taking KESIMPTA who was compensated for time. Individual results may vary.
Components of immune function may be maintained in KESIMPTA patients
lgG in the long term
lgG is created by B cells to work against specific antigens11
No decline in IgG was observed at the end of the Phase 3 ASCLEPIOS trials. Mean IgG levels remained stable for up to 5 years for KESIMPTA patients in the ALITHIOS extension analysis3,5,8
Phase 3 studies and post hoc analysis
T cells in the body
T cells help B cells produce antibodies and orchestrate the immune system response11
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
Phase 2 post hoc analysis
B cells in the spleen
B cells serve as antigen-presenting cells that activate T cells in the periphery13
SC administration of KESIMPTA is thought to promote preferential depletion of B cells in the lymph nodes14
Preclinical evidence suggests that KESIMPTA may spare B cells in the spleen, which may help maintain immune function15
Preclinical data
The precise mechanism by which KESIMPTA exerts its therapeutic effects is unknown. The clinical relevance of this data is unknown.
Serum immunoglobulin (Ig) levels can be predictors of infection risk when selecting B-cell therapy for relapsing MS patients
Immunoglobulins play a critical role in immune response by working to destroy pathogens, including bacteria and viruses3,16,17
Immunoglobulin M
The immune system's primary response to infection. Approximately 5% of antibodies in blood serum are IgM17,18
Immunoglobulin G
Protects the body from infection. Approximately 80% of antibodies in blood serum are IgG17,18
B-cell treatment may lead to Ig decline in relapsing MS patients, which may increase infection risk3
In the extension analysis
Patients on KESIMPTA maintained stable mean IgG levels for up to 5 years; mean IgM levels declined but remained above LLN5
KESIMPTA IgG/IgM data
In the Phase 3 ASCLEPIOS trials, no decline in IgG was observed at the end of the study3
In the extension analysis, mean IgG levels remained stable for up to 5 years in patients taking KESIMPTA5
IgG levels with KESIMPTA over 5 years5
Average IgG levels remained within the reference range (patients aged >18 years): 5.65-17.65 g/L.19
In the Phase 3 ASCLEPIOS trials, 14.3% of patients treated with KESIMPTA experienced a decrease in IgM3
In the long-term analysis, mean IgM declined over time but remained above the LLN for up to 5 years5
IgM levels with KESIMPTA over 5 years5
Average IgM levels remained within the reference range (patients aged >18 years): 0.4-2.3 g/L.19
§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.5
In the extension analysis, the overall incidence of serious infections was low5
Low incidence of serious infection (<2 per 100 PY): 5.38% of patients (n=106) experienced ≥1 serious infection within 1 month prior and until 1 month after any series of drops in IgG/IgM below LLN. Infections included herpes zoster, upper respiratory tract infection, urinary tract infection, COVID-19, bronchitis, pneumonia, pyelonephritis chronic, and COVID-19 pneumonia.
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.
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
No increased risk of severe or serious COVID-19 outcomes in patients taking KESIMPTA over 5 years in the ALITHIOS trial5,20*
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%).
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]).
†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.
BL, baseline; IgG, immunoglobulin G; IgM, immunoglobulin M; LLN, lower limit of normal; MOA, mechanism of action; MS, multiple sclerosis; PY, patient years; RMS, relapsing multiple sclerosis; SC, subcutaneous; SE, standard error.