Elzonris

SIDE EFFECTS

The following serious adverse drug reactions are described elsewhere in the labeling:

• Capillary Leak Syndrome [see WARNINGS AND PRECAUTIONS]
• Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
• Hepatotoxicity [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction 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 practice.

Safety of ELZONRIS was assessed in a single-arm clinical trial that included 94 adults with newly-diagnosed or relapsed/refractory myeloid malignancies, including 58 with BPDCN, treated with ELZONRIS 12 mcg/kg daily for 5 days of a 21-day cycle. The overall median number of cycles administered was 2 (range, 1-43), and 4 in patients with BPDCN (range, 1-43).

Two (2%) patients had fatal adverse reaction, both capillary leak syndrome. Overall, 10 (11%) patients discontinued treatment with ELZONRIS due to an adverse reaction; the most common adverse reactions resulting in treatment discontinuation were hepatic toxicities and CLS.

Table 3 summarizes the common (≥10%) adverse reactions with ELZONRIS in patients with myeloid malignancies. The rate of any given adverse reaction or lab abnormality was derived from all the reported events of that type.

Table 3: Adverse Reactions in ≥10% of Patients Receiving 12 mcg/kg of ELZONRIS

Table 4 summarizes the clinically-important laboratory abnormalities that occurred in ≥10% patients with myeloid malignancies treated with ELZONRIS.

Table 4: Selected Laboratory Abnormalities in Patients Receiving 12 mcg/kg of ELZONRIS

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 medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to ELZONRIS with the incidences of antibodies to other products may be misleading.

Immune response to ELZONRIS was evaluated by assessment of serum binding reactivity against ELZONRIS (anti-drug antibodies; ADA) and neutralizing antibodies by inhibition of functional activity. Immune response to ELZONRIS was assessed using two immunoassays. The first assay detected reactivity directed against ELZONRIS (ADA), and the second assay detected reactivity against the interleukin-3 (IL-3) portion of ELZONRIS. Two cell-based assays were used to investigate the presence of neutralizing antibodies by inhibition of a cell-based functional activity.

The presence of ADA had a clinically significant effect on the pharmacokinetics of tagraxofusp-erzs [see CLINICAL PHARMACOLOGY]. In 130 patients treated with ELZONRIS in 4 clinical trials:

• 96% (115/120) of patients evaluable for the presence of pre-existing ADA at baseline before treatment were confirmed positive with 21% being positive for the presence of neutralizing antibodies. The high prevalence of ADA at baseline was anticipated due to diphtheria immunization.
• 99% (107/108) of patients evaluable for treatment-emergent ADA tested positive with most patients showing an increase in ADA titer by the end of Cycle 2 of ELZONRIS.
• 85% (86/101) of ADA-positive patients evaluable for the presence of neutralizing antibodies were neutralizing antibody-positive.
• 68% (73/108) of patients evaluable for treatment-emergent anti-IL-3 antibodies tested positive with most patients testing positive by Cycle 3 of ELZONRIS.

Read the entire FDA prescribing information for Elzonris (Tagraxofusp-erzs Injection)