KESIMPTA (Page 2 of 8)

5.2 Injection-Related Reactions

In Study 1 and Study 2, 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 teriflunomide who received matching placebo injections, respectively [see Adverse Reactions (6.1) and Clinical Studies (14)].

Injection-related reactions with systemic symptoms observed in clinical studies occurred most commonly within 24 hours of the first injection, but were also observed with later injections. Symptoms observed included fever, headache, myalgia, chills, and fatigue, and were predominantly (99.8%) mild to moderate in severity. There were no life-threatening injection reactions in the RMS clinical studies.

Local injection-site reaction symptoms observed in clinical studies included erythema, swelling, itching, and pain.

Only limited benefit of premedication with corticosteroids, antihistamines, or acetaminophen was observed in RMS clinical studies. The first injection of KESIMPTA should be performed under the guidance of an appropriately trained healthcare professional. If injection-related reactions occur, symptomatic treatment is recommended.

5.3 Reduction in Immunoglobulins

As expected with any B-cell depleting therapy, decreased immunoglobulin levels were observed. Decrease in immunoglobulin M (IgM) was reported in 7.7% of patients treated with KESIMPTA compared to 3.1% of patients treated with teriflunomide in RMS clinical trials [see Adverse Reactions (6.1)]. Treatment was discontinued because of decreased immunoglobulins in 3.4% of patients treated with KESIMPTA and in 0.8% of patients treated with teriflunomide. No decline in immunoglobulin G (IgG) was observed at the end of the study. 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.

5.4 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 [see Use in Specific Populations (8.1)].

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are discussed in greater detail elsewhere in the labeling:

  • Infections [see Warnings and Precautions (5.1)]
  • Injection-Related Reactions [see Warnings and Precautions (5.2)]
  • Reduction in Immunoglobulins [see Warnings and Precautions (5.3)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Approximately 1500 patients with RMS received KESIMPTA in clinical studies. In Study 1 and Study 2, 1882 patients with RMS were randomized, 946 of whom were treated with KESIMPTA for a median duration of 85 weeks; 33% of patients receiving KESIMPTA were treated for up to 120 weeks [see Clinical Studies (14.1)]. The most common adverse reactions occurring in greater than 10% of patients treated with KESIMPTA and more frequently than in patients treated with teriflunomide were upper respiratory tract infections, injection-related reactions (systemic), headache, and injection-site reactions (local). The most common cause of discontinuation in patients treated with KESIMPTA was low immunoglobulin M (3.3%), defined in trial protocols as IgM at 10% below the lower limit of normal (LLN).

Table 1 summarizes the adverse drug reactions that occurred in Study 1 and Study 2.

Table 1: Adverse Reactions in Patients with RMS with an Incidence of at Least 5% with KESIMPTA and a Greater Incidence Than Teriflunomide (Pooled Study 1 and Study 2)
a Includes the following: nasopharyngitis, upper respiratory tract infection, influenza, sinusitis, pharyngitis, rhinitis, viral upperrespiratory infection, tonsillitis, acute sinusitis, pharyngotonsillitis, laryngitis, pharyngitis streptococcal, viral rhinitis, sinusitisbacterial, tonsillitis bacterial, viral pharyngitis, viral tonsillitis, chronic sinusitis, nasal herpes, tracheitis.
Adverse Reactions KESIMPTA 20 mgN = 946% Teriflunomide 14 mgN = 936%
Upper respiratory tract infectionsa 39 38
Injection-related reactions (systemic) 21 15
Headache 13 12
Injection-site reactions (local) 11 6
Urinary tract infection 10 8
Back pain 8 6
Blood immunoglobulin M decreased 6 2

Injection-Related Reactions and Injection-Site Reactions

The incidence of injection-related reactions (systemic) was highest with the first injection (14.4%), decreasing with subsequent injections (4.4% with second, less than 3% with third injection). Injection-related reactions were mostly (99.8%) mild to moderate in severity. Two (0.2%) patients treated with KESIMPTA reported serious injection-related reactions. There were no life-threatening injection-related reactions. Most frequently reported symptoms (2% or greater) included fever, headache, myalgia, chills, and fatigue.

In addition to systemic injection-related reactions, local reactions at the administration site were very common. Local injection-site reactions were all mild to moderate in severity. The most frequently reported symptoms (2% or greater) included erythema, pain, itching, and swelling [see Warnings and Precautions (5.2)].

Laboratory Abnormalities

Immunoglobulins

In Study 1 and Study 2, a decrease in the mean level of IgM was observed in KESIMPTA-treated patients but was not associated with an increased risk of infections [see Warnings and Precautions (5.3)]. In 14.3% of patients in Study 1 and Study 2, treatment with KESIMPTA resulted in a decrease in a serum IgM that reached a value below 0.34 g/dL. KESIMPTA was associated with a decrease of 4.3% in mean IgG levels after 48 weeks of treatment and an increase of 2.2% after 96 weeks.

6.2 Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medication, and the underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other ofatumumab products may be misleading.

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. There was no impact of positive ADA titers on PK, safety profile or B-cell kinetics in any patient; however, these data are not adequate to assess the impact of ADAs on the safety and efficacy of KESIMPTA.

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