From: Treatment Perspectives <education@treatmentperspectives.com>
To: [HCP email]
Subject Line 1: See how an RMS treatment option affected immunoglobulin levels in a Phase 3 study
Preheader: A newsletter on safety data for an RMS treatment option
|
Information from Industry
Content developed under the direction and sponsorship of Novartis Pharmaceuticals Corporation
|
| See below for pivotal results and safety data for approximately 2000 KESIMPTA® (ofatumumab) patients with up to 3.5 years of exposure |
 |
|
Dear [HCP name],
|
Trust an established safety profile... |
|
|
|
|
The efficacy and safety of KESIMPTA® vs teriflunomide were evaluated in 2 randomized, double-blind, active-controlled, Phase 3 pivotal studies with identical design in patients with relapsing forms of MS: ASCLEPIOS I and II.2
Rate of infections
| • |
The overall rate of infections and serious infections in patients treated with KESIMPTA was similar to teriflunomide (51.6% vs 52.7%, and 2.5% vs 1.8%, respectively)2 |
Treatment discontinuations
| • |
Pooled data from both clinical trials show that treatment discontinuation rates due to adverse events were similar between KESIMPTA (5.7%) and teriflunomide (5.2%)3 |
| • |
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 lower limit of normal (LLN)2 |
|
| * |
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. |
|
...that is tried through 3.5 years1† |
|
| • |
The nature and frequency of the most common adverse events (AEs) were comparable with those reported in ASCLEPIOS I and II1 |
| • |
In the overall population, the proportion of patients with AEs leading to discontinuation (5.8%) were consistent with those observed in the pivotal trials (5.7%) with KESIMPTA1,3 |
| • |
Serious infections occurred in less than 3% of the overall safety population1 |
| • |
No opportunistic infections or progressive multifocal leukoencephalopathy events were reported, and the risk of malignancies did not increase1 |
| • |
Two deaths were reported, both in the continuous KESIMPTA group, and neither were reported as related to KESIMPTA1 |
| • |
No conclusions of clinical outcomes can be drawn |
|
| † |
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. 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.1 |
| ‡ |
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”. |
|
Components of immune function may be maintained
in KESIMPTA patients1,2,4-7 |
|
| • |
Phase 3 studies and post hoc analysis: No decline in IgG was observed at the end of the Phase 3 ASCLEPIOS trials. Mean IgG levels remained stable for up to 3.5 years for KESIMPTA patients in the extension analysis1,2† |
| • |
Phase 2 post hoc analysis: T cells remained largely unaffected in KESIMPTA patients, as shown by 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 centers7 |
| • |
Preclinical data: Preferential depletion of B cells in the lymph nodes is thought to be promoted by subcutaneous administration of KESIMPTA. KESIMPTA may spare B cells in the spleen, which may help maintain immune function, as suggested by preclinical evidence4,6 |
| • |
The precise mechanism by which KESIMPTA exerts its therapeutic effects is unknown. The clinical relevance of this data is unknown |
|
In the extension study analysis, patients on KESIMPTA maintained stable mean IgG levels for up to 3.5 years; mean IgM levels declined but remained above LLN1 |
|
|
Serum IgG levels from baseline over time1
|
| • |
No decline in IgG levels were observed at the end of the Phase 3 ASCLEPIOS I and II trials for patients on KESIMPTA2 |
| • |
In the extension analysis, mean IgG levels remained stable for up to 3.5 years in patients taking KESIMPTA1 |
|
|
Serum IgM levels from baseline over time1
|
| • |
In the Phase 3 ASCLEPIOS I and II trials, 14.3% of patients treated with KESIMPTA experienced a decrease in serum IgM levels that reached a value below 0.34 g/dL2 |
| • |
In the extension analysis, mean IgM levels declined over time, but remained above the LLN for up to 3.5 years1 |
OMB=ofatumumab; R1=the first patient with first treatment-emergent assessment in OMB period after switching to OMB (72 weeks); R2=the last patient with last treatment-emergent assessment in TER period before switching to OMB (120 weeks); SE=standard error; TER=teriflunomide.
| § |
Switching period refers to the patients started with teriflunomide and not applicable to the patients treated with ofatumumab in core period. |
|
|
 |
| Dr Barry Hendin, Center for Neurology and Spine |
|
|
No increased risk of serious infection associated with change in IgG/IgM levels was observed for KESIMPTA at 3.5 years, in extension study analysis1
EAIR=exposure-adjusted incidence rate.
Time at risk for this group of patients is defined as the sum of duration of such episodes until the onset of serious infection.1
For all pooled analyses, a fixed value of LLN (using ALITHIOS study reference) was used. LLN for IgG: 5.65 g/L; IgM: 0.4 g/L.
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.2
|
| • |
Analysis and comparison: Association of infections occurring in conjunction with a decrease in either IgM or IgG levels below LLN, 1 month prior and until 1 month after detection of any series of decreases in IgM or IgG levels, analyzed and compared with infections reported in patients who maintained normal Ig levels (≥LLN)1 |
| • |
Risk of serious infection was low in the overall study population (2.9%)1 |
| • |
No association was observed between decreased Ig levels below LLN and a risk of serious infections in patients treated with KESIMPTA1 |
| |
◦ |
3 patients experienced a serious infection within 1 month of IgM levels dropping below LLN (herpes zoster [1 patient], upper respiratory tract infection [1 patient], urinary tract infection [1 patient])1 |
| |
◦ |
1 patient experienced a serious infection within 1 month of IgG levels dropping below LLN (pneumonia)1 |
|
 |
| Dr Mitzi Joi Williams, Joi Life Wellness Group |
|
|
|
|
Hear Dr Barry Hendin answer your most frequently asked questions about KESIMPTA and its effect on immunoglobulin levels in this interactive video
|
| 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.
|
|
|
| References 1. 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 [published online ahead of print, 2022 Mar 1]. Mult Scler. 2022;1‐15. 2. Kesimpta [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2020. 3. Data on file. OMB157G (ofatumumab). Summary of clinical safety. Novartis Pharmaceuticals Corp; East Hanover, NJ. January 2020. 4. Torres JB, Sealey M, Kneuer R, et al. Distribution and efficacy of ofatumumab and ocrelizumab in humanized‐CD20 mice following subcutaneous or intravenous administration. Neurology. 2019;92(suppl 15):2.2‐052. 5. Hauser SL, Bar‐Or A, Cohen JA, et al. Ofatumumab vs teriflunomide in relapsing multiple sclerosis: analysis of no evidence of disease activity (NEDA‐3) from ASCLEPIOS I and II trials. LB62. Poster presented at: 6th Congress of the European Academy of Neurology; May 23‐26, 2020; Virtual. 6. 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. 7. 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. 8. Data on file. Novartis Pharmaceuticals Corp; East Hanover, NJ. August 2021. |
|
KESIMPTA and the KESIMPTA logo are registered trademarks of Novartis AG.
|
| |
| |
|
|
| |
This is a service from ConneXion360, LLC.
To ensure you continue to receive these emails, please add education@treatmentperspectives.com
to your address book. Your participation in this activity is governed by the ConneXion360
Privacy Policy and Terms of Use.
If you no longer wish to receive emails from ConneXion360, click here. |
| |
This communication is provided by:
ConneXion360, LLC, 14901 Quorum Drive, Suite 650, Dallas, TX 75254 |
| |
|
