Niktimvo Drug Information

NIKTIMVO is indicated for the treatment of chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg.

Recommended Dosage

For patients weighing at least 40 kg, administer NIKTIMVO 0.3 mg/kg, up to a maximum dose of 35 mg, as an intravenous infusion over 30 minutes every 2 weeks until progression or unacceptable toxicity.

Dosage Modifications for Adverse Reactions

Monitor aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatine phosphokinase (CPK), amylase, and lipase prior to the start of NIKTIMVO therapy, every 2 weeks for the first month, and every 1 to 2 months thereafter until abnormalities are resolved. For recommended NIKTIMVO dosage modifications due to adverse reactions, see Table 1. Preparation Use aseptic technique to prepare NIKTIMVO.

Visually inspect the vial for particulate matter and discoloration prior to dilution. NIKTIMVO is a slightly opalescent, pale brownish yellow solution. Discard the vial if the solution is cloudy, discolored, or contains visible particles.

Do not shake the vial. Determine the dose and total volume of NIKTIMVO solution needed. Dilution Withdraw the calculated volume of NIKTIMVO solution from the vial and add it into an intravenous infusion bag made of polyvinyl chloride (PVC), polyolefin, polyolefin with polyamide, or ethylene vinyl acetate (EVA) containing 0.9% Sodium Chloride Injection to achieve a final concentration between the range of 0.24 mg/mL and 0.75 mg/mL.

Discard vial with any unused portion. Mix diluted solution by gentle inversion. Do not shake.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The diluted solution is a clear to slightly opalescent, colorless solution that may contain trace amounts of translucent to white particles. Discard if the solution is cloudy, discolored, or contains extraneous particulate matter other than trace amounts of translucent to white particles.

Storage of diluted NIKTIMVO solution Immediately use diluted NIKTIMVO solution. If not used immediately, the diluted solution can be stored: - At room temperature for no more than 4 hours from the time of preparation to the end of the infusion. OR - Refrigerated at 2°C to 8°C (36°F to 46°F) for no more than 24 hours.

If refrigerated, allow the diluted solution to come to room temperature prior to administration. The diluted solution must be administered within 4 hours (including infusion time) once it is removed from the refrigerator. Do not freeze or shake the diluted solution.

Administration Administer diluted NIKTIMVO solution by intravenous infusion over 30 minutes through a dedicated infusion line that includes a sterile, low-protein binding 0.2-micron in-line or add-on polyethersulfone (PES) filter. Do not co‑administer other drugs through the same infusion line. After administration, flush the infusion line with 0.9% Sodium Chloride Injection.

Clinical Trial 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. Chronic Graft-Versus-Host Disease The safety of NIKTIMVO was evaluated in 79 adult and pediatric patients with cGVHD treated with NIKTIMVO 0.3 mg/kg intravenously every 2 weeks in the AGAVE‑201 trial. Serious adverse reactions occurred in 44% of patients who received NIKTIMVO.

Serious adverse reactions in more than 2 patients included infection (pathogen unspecified), viral infection, and respiratory failure. Permanent discontinuation of NIKTIMVO due to an adverse reaction occurred in 10% of patients and dose reduction due to adverse reaction occurred in 8% of patients. Dose interruptions due to an adverse reaction occurred in 44% of patients.

The adverse reactions leading to dose interruption in more than 2 patients were viral infection, infection (pathogen unspecified), bacterial infection, musculoskeletal pain, and pyrexia. The most common (≥ 15%) adverse reactions, including laboratory abnormalities, were increased AST, infection (pathogen unspecified), increased ALT, decreased phosphate, decreased hemoglobin, viral infection, increased gamma glutamyl transferase (GGT), musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased CPK, increased ALP, nausea, headache, diarrhea, cough, bacterial infection, pyrexia, and dyspnea. Table 2 summarizes the nonlaboratory adverse reactions in AGAVE-201.

Table 3: Selected Laboratory Abnormalities in Patients with cGVHD Who Received NIKTIMVO in AGAVE- 0 Immunogenicity: Anti-Drug Antibody–Associated Adverse Reactions In 276 patients with cGVHD who received NIKTIMVO in clinical trials, among the patients who developed anti-drug antibodies (ADAs), hypersensitivity reactions occurred in 26% (13/50) of patients with neutralizing antibodies (NAb) and in 4% (2/45) of those without NAb.

Pregnancy Risk Summary Based on its mechanism of action, NIKTIMVO may cause fetal harm when administered to pregnant women. There are no available data on the use of NIKTIMVO in pregnant women to evaluate for a drug-associated risk. No animal reproductive and developmental toxicity studies have been conducted with axatilimab-csfr.

Targeted mutation of CSF-1R or CSF-1 in rodent models results in prenatal and perinatal death, deficits in growth, and pleiotropic impact on multiple organ systems, including skeletal and reproductive. Regulation by CSF-1R on non-mononuclear phagocytic cells and macrophages plays a role in the innate immune protection of the fetus and in pregnancy maintenance and embryo-fetal development. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, NIKTIMVO has the potential to be transmitted from the mother to the developing fetus.

Advise women of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.

Pediatric Use The safety and effectiveness of NIKTIMVO for the treatment of cGVHD after failure of at least two prior lines of systemic therapy have been established in pediatric patients weighing at least 40 kg. The safety and effectiveness of NIKTIMVO have not been established in pediatric patients weighing less than 40 kg. Compared to adult and pediatric patients weighing 40 kg and above, patients weighing less than 40 kg had lower maximum concentration, trough concentration, and average concentration at the same weight-based dosage.

Based on findings of thickening of the growth plate and metaphysis and/or degeneration of the growth plate in the femur in animals, monitor bone growth and development in pediatric patients.