NIKTIMVO Solution for injection Ref.[115487] Active ingredients: Axatilimab

5.1 Infusion-Related Reactions

NIKTIMVO can cause infusion-related reactions. Infusion-related reactions, including hypersensitivity reactions, occurred in 18% of patients who received NIKTIMVO in the clinical trial (AGAVE-201), with Grade 3 or 4 reactions in 1.3% [see Adverse Reactions (6.1)].

Premedicate with an antihistamine and an antipyretic for patients who have previously experienced an infusion-related reaction to NIKTIMVO [see Dosage and Administration (2.2)]. Monitor patients for signs and symptoms of infusion-related reactions, including fever, chills, rash, flushing, dyspnea, and hypertension. Interrupt or slow the rate of infusion or permanently discontinue NIKTIMVO based on severity of the reaction [see Dosage and Administration (2.2)].

5.2 Embryo-Fetal Toxicity

Based on its mechanism of action, NIKTIMVO may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with NIKTIMVO and for 30 days after the last dose [see Use in Specific Populations (8.1, 8.3)].

The following adverse reactions are described elsewhere in the labeling.

• Infusion-Related Reactions [see Warnings and Precautions (5.1)]

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 [see Clinical Studies (14)]. The median duration of treatment was 10.3 months (range: 0.5 to 28.6 months), and 73.4% were treated for more than 6 months.

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 2. Adverse Reactions in ≥10% of Patients With cGVHD Who Received NIKTIMVO in AGAVE-201:

Graded according to NCI CTCAE v5.0.
^* Includes abscess jaw, atypical pneumonia, bacteremia, bronchitis, conjunctivitis, cystitis, device-related infection, enterocolitis infectious, gastroenteritis, gastrointestinal infection, groin abscess, hordeolum, liver abscess, nasopharyngitis, otitis media, otitis media acute, pneumonia, respiratory tract infection, rhinitis, sepsis, sinusitis, tooth infection, upper respiratory tract infection, urinary tract infection, and wound infection.
^† Includes adenoviral upper respiratory infection, BK virus infection, COVID-19, coronavirus infection, enterovirus infection, gastroenteritis astroviral, gastroenteritis viral, herpes simplex, herpes zoster, influenza, metapneumovirus bronchiolitis, metapneumovirus infection, norovirus infection, oral viral infection, parainfluenza viral bronchitis, parainfluenza virus infection, respiratory syncytial virus infection, rhinovirus infection, viral infection, and viral upper respiratory tract infection.
^‡ Includes bacterial diarrhea, bacterial vaginosis, campylobacter gastroenteritis, campylobacter infection, cellulitis, clostridium difficile colitis, clostridium difficile infection, enterococcal infection, erysipelas, hemophilus infection, lower respiratory tract infection bacterial, pseudomonal skin infection, staphylococcal bacteremia, staphylococcal infection, stenotrophomonas infection, streptococcal infection, and urinary tract infection enterococcal.
^§ Includes arthralgia, back pain, flank pain, musculoskeletal pain, myalgia, pain in extremity.
^¶ Includes asthenia, fatigue, and malaise.
^# Includes localized edema and peripheral edema.
^Þ Includes nausea and vomiting.
^ß Includes colitis and diarrhea.
^à Includes headache and migraine.
^è Includes dizziness and dizziness postural.
^ð Includes cough and productive cough.
^ø Includes dyspnea and dyspnea exertional.
^ý Includes bronchospasm, flushing, hot flush, hypersensitivity, infusion-related hypersensitivity reaction, infusion-related reaction, and urticaria.
^£ Includes contusion, epistaxis, hematochezia, hematoma, and vaginal hemorrhage.
^¥ Includes dermatitis bullous, dermatitis exfoliative generalized, rash, and rash maculo-papular.

Clinically relevant adverse reactions in <10% of patients who received NIKTIMVO included:

• Eye disorders: periorbital edema
• Skin and subcutaneous skin disorders: pruritus
• Vascular disorders: hypertension

Table 3 summarizes the laboratory abnormalities in AGAVE-201.

Table 3. Selected Laboratory Abnormalities in Patients with cGVHD Who Received NIKTIMVO in AGAVE-201:

NA = not applicable.
^* The denominator used to calculate the rate varied from 78 to 79 based on the number of patients with at least 1 post-treatment value.

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 [see Clinical Pharmacology (12.6)].

Risk Summary

Based on its mechanism of action, NIKTIMVO may cause fetal harm when administered to pregnant women [see Clinical Pharmacology (12.1)]. 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 2% to 4% and 15% to 20%, respectively.

Risk Summary

There are no data on the presence of axatilimab-csfr in human milk or the effects on the breastfed child or milk production. Maternal IgG is known to be present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 30 days after the last dose of NIKTIMVO.

NIKTIMVO may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].

Pregnancy Testing

Verify pregnancy status in females of reproductive potential prior to initiating NIKTIMVO [see Use in Specific Populations (8.1)].

Contraception

Females

Advise females of reproductive potential to use effective contraception during treatment with NIKTIMVO and for 30 days after the last dose of NIKTIMVO.

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. Use of NIKTIMVO in pediatric patients weighing at least 40 kg is supported by evidence from clinical trials that included 3 children (ages 6 to less than 12 years old) and 5 adolescents (ages 12 to less than 17 years old) [see Clinical Studies (14)]. 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 [see Nonclinical Toxicology (13.2)].

Of the 79 patients with cGVHD treated with NIKTIMVO, 21 (26.6%) were 65 years and older, and 2 (2.5%) were 75 years and older [see Clinical Studies (14)]. No overall differences in the safety or effectiveness of NIKTIMVO have been observed between patients 65 years of age and older and younger patients.