Tagraxofusp

Risk Summary

Based on its mechanism of action, tagraxofusp has the potential for adverse effects on embryo-fetal development. There are no available data on tagraxofusp use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. Animal reproduction or developmental toxicity studies have not been conducted with tagraxofusp-erzs. Advise pregnant women of the potential risk to the fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4%, and 15% to 20%, respectively.

Risk Summary

No data are available regarding the presence of tagraxofusp in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children from tagraxofusp, breast feeding is not recommended during treatment and for 1 week after the last dose.

No studies have been conducted to assess the carcinogenic or genotoxic potential of tagraxofusp. Animal fertility studies have not been conducted with tagraxofusp-erzs.

• Capillary Leak Syndrome
• Hypersensitivity Reactions
• Hepatotoxicity

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 tagraxofusp 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 tagraxofusp 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 tagraxofusp due to an adverse reaction; the most common adverse reactions resulting in treatment discontinuation were hepatic toxicities and CLS.

Table 1 summarizes the common (≥10%) adverse reactions with tagraxofusp 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 1. Adverse Reactions in ≥10% of Patients Receiving 12 mcg/kg of Tagraxofusp:

¹ Capillary leak syndrome defined as any event reported as CLS during treatment with tagraxofusp or the occurrence of at least 2 of the following CLS manifestations within 7 days of each other: hypoalbuminemia (including albumin value less than 3.0 g/dL), edema (including weight increase of 5 kg or more), hypotension (including systolic blood pressure less than 90 mmHg).

Table 2 summarizes the clinically-important laboratory abnormalities that occurred in ≥10% patients with myeloid malignancies treated with tagraxofusp.

Table 2. Selected Laboratory Abnormalities in Patients Receiving 12 mcg/kg of Tagraxofusp: