Niktimvo Drug Information
Generic name: AXATILIMAB-CSFR
Colony Stimulating Factor-1 Receptor Blocker [EPC]
Uses of 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. NIKTIMVO is a colony stimulating factor-1 receptor (CSF-1R)-blocking antibody 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.
Dosage & Administration of Niktimvo
| AST = aspartate aminotransferase; ALT = alanine aminotransferase; ULN = upper limit of normal; ALP = alkaline phosphatase; CPK = creatine phosphokinase. | |
|---|---|
| Infusion-related reactions | Grade 1 or 2 |
| Grade 3 or 4 | Permanently discontinue NIKTIMVO. |
| Elevation of AST or ALT (on the day of dosing) | Grade 3 with total bilirubin ≤ Grade 1 |
| Elevation of AST or ALT (regardless of the time of the reaction) | ALT or AST ≥ 3 times ULN with total bilirubin ≥ 2 times ULN and ALP < 2 times ULN |
| Grade 4 | Permanently discontinue NIKTIMVO. |
| Elevation of CPK, amylase, or lipase | ≥ Grade 3 |
| Symptomatic ≥ Grade 3 | Permanently discontinue NIKTIMVO. |
| Other Nonhematologic Adverse Reactions | Grade 3 |
| Grade 4 | Permanently discontinue NIKTIMVO. |
Side Effects of Niktimvo
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 . 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. Adverse Reaction NIKTIMVO 0.3 mg/kg intravenously every 2 weeks (N = 79) All Grades (%) Grades 3-4 (%) Infections and infestations Infection (pathogen unspecified) 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. 57 14 Viral 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. 43 15 Bacterial 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. 15 8 Musculoskeletal and connective tissue disorders Musculoskeletal pain Includes arthralgia, back pain, flank pain, musculoskeletal pain, myalgia, pain in extremity. 35 3 General disorders and administration site conditions Fatigue Includes asthenia, fatigue, and malaise. 32 4 Pyrexia 15 1 Edema Includes localized edema and peripheral edema. 13 1 Gastrointestinal disorders Nausea Includes nausea and vomiting. 23 3 Diarrhea Includes colitis and diarrhea. 18 5 Nervous system disorders Headache Includes headache and migraine. 20 1 Dizziness Includes dizziness and dizziness postural. 11 0 Respiratory, thoracic and mediastinal disorders Cough Includes cough and productive cough. 18 0 Dyspnea Includes dyspnea and dyspnea exertional. 15 3 Immune system disorders Drug hypersensitivity Includes bronchospasm, flushing, hot flush, hypersensitivity, infusion-related hypersensitivity reaction, infusion-related reaction, and urticaria. 13 3 Metabolism and nutrition disorders Decreased appetite 11 4 Vascular disorders Hemorrhage Includes contusion, epistaxis, hematochezia, hematoma, and vaginal hemorrhage. 11 1 Skin and subcutaneous tissue disorders Rash Includes dermatitis bullous, dermatitis exfoliative generalized, rash, and rash maculo-papular. 10 0 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. Laboratory Abnormality NIKTIMVO 0.3 mg/kg intravenously every 2 weeks (N=79) All Grades 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. (%) Grade 3 or 4 (%) Hematology Decreased hemoglobin 48 4 Chemistry Increased aspartate aminotransferase 61 5 Increased alanine aminotransferase 51 3 Decreased phosphate 51 NA Increased gamma glutamyl transferase 39 4 Increased lipase 34 3 Increased amylase 32 0 Increased calcium 31 1 Increased alkaline phosphatase 28 0 Increased creatine phosphokinase 25 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 .
Warnings & Cautions for Niktimvo
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% . Premedicate with an antihistamine and an antipyretic for patients who have previously experienced an infusion-related reaction to NIKTIMVO . 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 .
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 .
Pregnancy Safety for Niktimvo
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 2% to 4% and 15% to 20%, respectively.
Pediatric Use of Niktimvo
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. 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) . 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 .
Clinical Studies of Niktimvo
The efficacy of NIKTIMVO was evaluated in AGAVE-201 (NCT04710576), a randomized, open-label, multicenter study in adult and pediatric patients with recurrent or refractory cGVHD who had received at least 2 lines of systemic therapy and required additional treatment. Patients with platelet count ≥ 50 × 10 9 /L, absolute neutrophil count ≥ 1 × 10 9 /L, ALT and AST ≤ 2.5 × ULN (≤ 5 × ULN if liver cGVHD was present), total bilirubin ≤ 1.5 × ULN, and creatinine clearance ≥ 30 mL/minute were eligible. Patients with uncontrolled infections were not eligible.
Treatment consisted of NIKTIMVO 0.3 mg/kg administered intravenously every 2 weeks until disease progression, lack of efficacy by 9 months, or unacceptable toxicity. Continued treatment with GVHD prophylaxis and standard care systemic cGVHD therapies were permitted as long as the patient had been on a stable dose for at least 2 weeks prior to study. Initiation of new systemic cGVHD therapy while on study was not permitted.
Demographics and baseline characteristics of the 79 patients treated with NIKTIMVO 0.3 mg/kg every 2 weeks in AGAVE-201 are summarized in Table 4. Table 4: Demographics and Baseline Characteristics of Patients With cGVHD NIKTIMVO 0.3 mg/kg every 2 weeks (N = 79) Median age, years (range) 50 Age ≥ 65 years, n (%) 21 Male, n (%) 46 Race, n (%) White 67 Asian 4 Black 2 Other 1 Not reported 5 Median (range) time (months) from cGVHD diagnosis 47 ≥ 4 Organs involved, n (%) 45 Median (range) number of prior lines of therapy 4 Number of prior lines of therapy, n (%) 2 11 3 14 4 17 ≥ 5 37 Prior cGVHD treatment with ibrutinib, n (%) 27 Prior cGVHD treatment with ruxolitinib, n (%) 57 Prior cGVHD treatment with belumosudil, n (%) 16 Refractory to last therapy, n (%) 37 Severe cGVHD, n (%) 63 Median (range) Global Severity Rating 7 Median (range) modified Lee Symptom Scale Score at baseline 24 Median (range) corticosteroid dose at baseline (PE/kg) Prednisone equivalents/kilogram/day. 0.21 The efficacy of NIKTIMVO was based on overall response rate (ORR) through Cycle 7 Day 1, where overall response included complete response or partial response according to the 2014 NIH Consensus Development Project on Response Criteria. The ORR results from AGAVE-201 for the 0.3 mg/kg every 2 weeks dosage regimen are presented in Table 5. The median time to first response was 1.5 months (range, 0.9 to 5.1 months). The median duration of response, calculated from first response to progression, death, or new systemic therapies for cGVHD, was 1.9 months (95% CI: 1.6, 3.5). In patients who achieved response, no death or new systemic therapy initiation occurred in 60% (95% CI: 43, 74) of patients for at least 12 months since response. Table 5: Efficacy Results From AGAVE-201 CI = confidence interval.
Endpoint NIKTIMVO 0.3 mg/kg every 2 weeks (N = 79) Overall response rate, n (%) 95% CI Complete response, n (%) Partial response, n (%) 59 (75%) 64, 84 0 (0%) 59 (75%) ORR results were supported by exploratory analyses of patient-reported symptom bother which showed at least a 7-point decrease in the modified Lee Symptom Scale score through Cycle 7 Day 1 in 56% (95% CI: 44, 67) of patients.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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