Enjaymo Drug Information
Generic name: SUTIMLIMAB-JOME
Classical Complement Pathway Inhibitor [EPC]
Uses of Enjaymo
is a classical complement inhibitor indicated for the treatment of hemolysis in adults with cold agglutinin disease (CAD). Cold Agglutinin Disease ENJAYMO (sutimlimab-jome) is indicated for the treatment of hemolysis in adults with cold agglutinin disease (CAD).
Dosage & Administration of Enjaymo
| Greater than or equal to 39 kg to less than 75 kg | 6,500 mg |
|---|---|
| 75 kg or greater | 7,500 mg |
Side Effects of Enjaymo
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. The safety of ENJAYMO in patients with a confirmed diagnosis of CAD was evaluated in a placebo-controlled study (CADENZA) in Part A (n=42) followed by an open-label single-arm study in Part B (n=39) and an open-label single-arm study (CARDINAL) (n=24) . The median duration of treatment exposure to ENJAYMO was 104 weeks (patients randomized to ENJAYMO in CADENZA Part A) and 93 weeks (patients randomized to placebo in CADENZA Part A) and 143 weeks for CARDINAL. CADENZA (Part A) Serious adverse reaction occurred in 2/22 (9%) patients who received ENJAYMO. Serious adverse reactions included Raynaud's phenomenon (n=1) and febrile infection (n=1). Permanent discontinuation of ENJAYMO due to an adverse reaction occurred in 2/22 (9%) patients. Adverse reactions which resulted in permanent discontinuation of ENJAYMO included Raynaud's phenomenon (n=1), acrocyanosis (n=1), and infusion related reactions (n=1). Dosage interruptions of ENJAYMO due to an adverse reaction occurred in 3/22 patients.
Adverse reactions which required dosage interruption included nasopharyngitis (n=1) and infusion related reaction (n=1), including pruritis (n=1) and chest discomfort (n=1). The most common adverse reactions (≥18%) reported in the CADENZA study were rhinitis, headache, hypertension, acrocyanosis, and Raynaud's phenomenon. Table 3: Adverse Reactions (≥10%) in Patients Who Received ENJAYMO with a Difference Between Arms of >5% Compared to Placebo in the CADENZA Study (Part A) Adverse Reactions ENJAYMO (N=22) Placebo (N=20) Headache 5 (23%) 2 (10%) Hypertension 5 (23%) 0 Rhinitis 4 (18%) 0 Acrocyanosis 4 (18%) 0 Raynaud's phenomenon 4 (18%) 0 CARDINAL Serious adverse reactions occurred in 10/24 (42%) patients who received ENJAYMO. The most common adverse reaction (>5%) was acrocyanosis (n=2). A fatal adverse reaction of pneumonia klebsiella occurred in one patient who received ENJAYMO. Permanent discontinuation of ENJAYMO due to an adverse reaction occurred in 2/24 (8%) patients. Adverse reactions which resulted in permanent discontinuation of ENJAYMO included pneumonia klebsiella (n=1) and acrocyanosis (n=2). Dosage interruptions of ENJAYMO due to an adverse reaction occurred in 7/24 patients.
Adverse reactions which required dosage interruption included pneumonia, COVID-19 pneumonia, abdominal pain upper, urinary tract infection bacterial, urosepsis, acrocyanosis, viral infection, blood creatinine increased and infusion-related reaction. The most common adverse reaction (≥25%) reported in the CARDINAL study were urinary tract infection, respiratory tract infection, bacterial infection, dizziness, fatigue, peripheral edema, arthralgia, cough, hypertension, and nausea. Table 4: Adverse Reactions (≥15%) in Patients Receiving ENJAYMO in the CARDINAL Study Adverse Reaction/Body System n (%) (N=24) Please note: if a subject has multiple events in a grouped term the subject is only counted once.
The following terms were combined for the analysis: INFECTIONS AND INFESTATIONS Urinary tract infection Urinary Tract Infection includes cystitis, urosepsis 9 (38%) Respiratory tract infection Respiratory tract infection includes upper respiratory tract infection, bronchitis, lower respiratory tract infection, COVID-19 pneumonia 6 (25%) Bacterial infection Bacterial infection includes Escherichia urinary tract infection, urinary tract infection bacteria, cystitis bacterial, Escherichia sepsis, pneumococcal sepsis, pneumonia klebsiella, streptococcal sepsis, wound infection staphylococcal 6 (25%) Nasopharyngitis 5 (21%) Viral infection Viral infection includes oral herpes, herpes zoster, respiratory tract infection viral, viral upper respiratory tract infection, Herpes simplex viraemia 5 (21%) NERVOUS SYSTEM DISORDERS Dizziness Dizziness includes dizziness postural and vertigo 7 (29%) Headache 5 (21%) GENERAL DISORDERS Fatigue Fatigue includes asthenia, malaise, mental fatigue 8 (33%) Peripheral edema Peripheral edema includes peripheral swelling 6 (25%) Pyrexia 5 (21%) MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS Arthralgia 6 (25%) VASCULAR DISORDERS Hypertension Hypertension includes, blood pressure increased, essential hypertension 6 (25%) Acrocyanosis 5 (21%) GASTROINTESTINAL DISORDERS Nausea 6 (25%) Abdominal pain Abdominal pain includes abdominal pain upper, abdominal tenderness 5 (21%) RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS Cough Cough includes productive cough 6 (25%) INJURY, POISONING AND PROCEDURAL COMPLICATIONS Infusion-related reaction Infusion related reaction includes stress cardiomyopathy, feeling cold (All occurred within 24 hours of start of ENJAYMO infusion) 4 (17%)
Warnings & Cautions for Enjaymo
Serious Infections Including Those Caused by Encapsulated Bacteria
ENJAYMO, a proximal classical complement C1s inhibitor, increases a patient's susceptibility to serious infections including those caused by encapsulated bacteria e.g. Neisseria meningitidis (any serogroup, including non-groupable strains), Streptococcus pneumoniae, and Haemophilus influenzae type B. Life-threatening and fatal infections with encapsulated bacteria have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors. Serious infections (bacterial and viral) were reported in 15% (10/66) of patients receiving ENJAYMO from the two phase 3 studies.
These infections included urinary tract infection with sepsis, respiratory tract infection, pneumonia, otomastoiditis, and skin infections One patient (1.5%) died due to klebsiella pneumonia. Complete or update vaccination against encapsulated bacteria at least 2 weeks prior to administration of the first dose of ENJAYMO, according to the most current ACIP recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations considering the chronic duration of therapy with ENJAYMO. Note that, ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information.
If urgent ENJAYMO therapy is indicated in a patient who is not up to date on their vaccines administer vaccine(s) as soon as possible. Vaccination does not eliminate the risk of serious encapsulated bacterial infections, despite development of antibodies following vaccination. Closely monitor patients for early signs and symptoms of serious infection and evaluate patients immediately if an infection is suspected.
If ENJAYMO treatment is administered to patients with active systemic infections, monitor closely for signs and symptoms of worsening infection. Some infections may become rapidly life-threatening or fatal if not recognized and treated promptly. Inform patients of these signs and symptoms and steps to be taken to seek immediate medical care.
Consider interruption of ENJAYMO treatment in patients who are undergoing treatment for serious infection. ENJAYMO has not been studied in patients with chronic systemic infections such as hepatitis B, hepatitis C, or HIV. Consider patients' immune status when initiating treatment with ENJAYMO.
Infusion-Related Reactions
ENJAYMO is contraindicated in patients with known hypersensitivity to sutimlimab-jome or any of the inactive ingredients . Administration of ENJAYMO may result in infusion-related reactions. In the two phase 3 studies, 19 of 66 (29%) patients treated with ENJAYMO experienced infusion-related reactions (e.g., shortness of breath, rapid heartbeat, nausea, flushing, headache, hypotension, chest discomfort, pruritus, rash, injection site reaction, and dizziness) were reported in patients from the two clinical studies. One patient permanently discontinued ENJAYMO due to an infusion-related reaction.
Monitor patients for infusion-related reactions and interrupt if a reaction occurs. Discontinue ENJAYMO infusion and institute appropriate supportive measures if signs of hypersensitivity reactions, such as cardiovascular instability or respiratory compromise, occur.
Risk of Autoimmune Disease
Based on its mechanism of action, ENJAYMO may potentially increase the risk for developing autoimmune diseases such as systemic lupus erythematosus (SLE). Development of systemic lupus erythematosus (SLE) has been associated with inherited classical complement deficiency. Patients with SLE or autoimmune disease with positive anti-nuclear antibody were excluded from clinical trials with ENJAYMO. In clinical trials, 3/66 (4.5%) patients developed a relapse or worsening of preexisting autoimmune disease. Monitor patients being treated with ENJAYMO for signs and symptoms and manage medically.
Recurrent Hemolysis After
ENJAYMO Discontinuation If treatment with ENJAYMO is interrupted, closely monitor patients for signs and symptoms of recurrent hemolysis, e.g., elevated levels of total bilirubin or lactate dehydrogenase (LDH) accompanied by a decrease in hemoglobin, or reappearance of symptoms such as fatigue, dyspnea, palpitations, or hemoglobinuria. Consider restarting ENJAYMO if signs and symptoms of hemolysis occur after discontinuation.
Pregnancy Safety for Enjaymo
Pregnancy Risk Summary There are no available data on ENJAYMO use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Human immunoglobulin G (IgG) antibodies are known to cross the placental barrier; therefore, sutimlimab-jome may be transmitted from the mother to the developing fetus. In animal reproduction studies, intravenous administration of sutimlimab-jome to pregnant monkeys during organogenesis at doses 2 to 3 times the maximum recommended human doses did not result in adverse effects on pregnancy or offspring development (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Data Animal data Pregnant monkeys were administered sutimlimab-jome at doses of 60 and 180 mg/kg/dose via 30-minute intravenous infusion once-weekly from gestation Day 20 to parturition (approximately 21 doses) resulting in exposures 2 to 3 times the human exposures at the maximum recommended doses, based on area under the curve (AUC). Sutimlimab-jome was detectable in infants born to pregnant females exposed to 180 mg/kg/week.
No effects on reproductive and developmental parameters were observed in maternal animals and offspring, respectively.
Pediatric Use of Enjaymo
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Contraindications for Enjaymo
is contraindicated in patients with known hypersensitivity to sutimlimab-jome or any of the inactive ingredients . ENJAYMO is contraindicated in patients with known hypersensitivity to sutimlimab-jome or any of the inactive ingredients.
Clinical Studies of Enjaymo
CADENZA
The efficacy of ENJAYMO was assessed in a placebo-controlled 6-month trial in 42 patients (CADENZA, NCT 03275454). Following the completion of the 6-month treatment period (Part A) in which 22 patients received ENJAYMO and 20 patients received placebo, 39 patients (19 patients on ENJAYMO and 20 patients on placebo) continued to receive ENJAYMO in a long-term safety and durability of response extension phase (Part B) for an additional 12 months following last patient out from Part A. The trial included a 9 week safety follow-up after the last dose of ENJAYMO. Patients with a confirmed diagnosis of CAD based on chronic hemolysis, polyspecific direct antiglobulin test (DAT), monospecific DAT specific for C3d, cold agglutinin titer ≥64 at 4°C, an IgG DAT ≤1+ and no history of transfusion within 6 months, or more than one blood transfusion in the 12 months prior to enrollment in the trial were administered 6.5 g or 7.5 g ENJAYMO (based on body weight) intravenously over approximately 60 minutes on Day 0, Day 7, and every 14 days thereafter; or placebo. Patients with cold agglutinin disease secondary to infection, rheumatologic disease, systemic lupus erythematosus, or overt hematologic malignancy were excluded, whereas patients with a history of or concomitant low-grade lymphoproliferative disease were not excluded. Major baseline characteristics of the study population are summarized in Table 5. Table 5: Baseline Characteristics of Patients Included in CADENZA Parameter Statistic CADENZA Placebo ENJAYMO N=20 N=22 Age Mean 68.2
Min, Max 51, 83 46, 88 Sex Male n (%) 4 5
Female 16 17 Body weight Mean, Kg 64.9
Min, Max 48, 95 39, 100 Hemoglobin Mean, g/dL 9.33 9.15 Bilirubin
(total) Placebo N=18 and ENJAYMO N= 20 in CADENZA, for bilirubin data excluding patients with either a positive or no available test result for Gilbert's syndrome. µmol/L 35.77 41.17 (1.75 × ULN) (2 × ULN) LDH U/L 380.8
History of transfusion Mean number of transfusions (range) Within last 6 months
0 0 Within last 12 months 0 0.14 FACIT ULN: Upper limit of normal, FACIT: Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue is measured on a scale of 0 (worst fatigue) to 52 (no fatigue) -Fatigue scale Mean 32.99 31.67 Efficacy was based on the proportion of patients who met the following criteria: an increase from baseline in Hgb level ≥1.5 g/dL at the treatment assessment time point (mean value from Weeks 23, 25, and 26), no blood transfusion from Week 5 through Week 26, and no treatment for CAD beyond what was permitted per protocol from Week 5 through Week 26. Efficacy was further assessed based on the effect of ENJAYMO on Hgb, laboratory measures of hemolysis including mean change from baseline in total bilirubin and LDH. Supportive efficacy data collected included transfusion usage after five weeks of treatment. In addition, mean change from baseline in symptoms and impacts of fatigue were assessed using a patient-reported outcome instrument, the FACIT-Fatigue (score range from 0 to 52 with higher scores indicating less fatigue). The data from this study demonstrated a statistically significant treatment effect of ENJAYMO over placebo in terms of the rate of patients who met the efficacy criteria (responder) as well as improving symptoms and impacts of fatigue (FACIT-Fatigue). The responder rate difference between ENJAYMO and placebo was 58.78% (95% CI: 34.6% to 82.96%) with a p-value of 0.0004. At the treatment assessment timepoint (TAT), 16 of 22 patients on ENJAYMO (72.7%; 95% CI: 49.8% to 89.3%) and 3 of 20 patients on placebo (15.0%; 95% CI: 3.2% to 37.9%) met primary criteria. Efficacy of ENJAYMO in the inhibition of hemolysis in patients with CAD was demonstrated across multiple end points as described in the table below (see Table 6 ). Table 6: Efficacy Results in Patients with CAD in the CADENZA Part A Study Parameter Statistic Placebo N=20 ENJAYMO N=22 Treatment Effect NC= Not calculated Responder A responder was defined as a patient with an increase from baseline in Hgb level ≥ 1.5 g/dL at the treatment assessment time point (mean value from Weeks 23, 25, and 26), no blood transfusion from Week 5 through Week 26, and no treatment for CAD beyond what was permitted per protocol from Week 5 through Week 26. n (%) 3 16 58.78 The Mantel-Haenszel stratum-weighted estimator of the rate difference with 95% CI was calculated using the Sato variance estimator.
The stratification factors are baseline hemoglobin (< median vs ≥ median) and geographic region (Asia/Other, North America, and Europe) p-value: <0.001 Hemoglobin Mean change from baseline (LS LS: Least Square, FACIT-Fatigue: Functional Assessment of Chronic Illness Therapy-Fatigue Scale Mean), g/dL 0.09 2.66 2.56 95% CI of LS Mean p-value: <0.001 Patients with mean change from baseline of: greater than or equal to 1.5 g/dL n (%) 3 16 NC Patients not receiving blood transfusion from Week 5 through Week 26 (transfusion avoidance) n (%) 16 18 NC Patients not receiving protocol-prohibited CAD medications from Week 5 through Week 26 Prohibited therapies included rituximab alone or in combination with cytotoxic agents n (%) 20 19 NC FACIT -Fatigue Mean change from baseline (LS Mean) 1.91 10.83 8.93 95% CI of LS Mean p-value: <0.001 During Part A, an increase in mean hemoglobin level of 2.02 g/dL was observed in patients on ENJAYMO at Week 3; in the placebo group the mean hemoglobin level decreased by 0.31g/dL. At treatment assessment timepoint, a mean decrease in bilirubin of 1.29 mg/dL compared to baseline was reported in patients on ENJAYMO (n=17) versus 0.11 mg/dL on placebo (n=18). In the ENJAYMO group, bilirubin levels normalized in 88.2% (n=15) of patients compared to 22.2% (n=4) of patients in the placebo arm. At treatment assessment timepoint, a mean decrease in LDH of 150.83 U/L compared to baseline was reported in patients on ENJAYMO (n=19) versus an increase of
U/L on placebo (n=20).
In the ENJAYMO group, LDH levels were < 1.5 × ULN in 94.7% (n=18) of patients compared to 70% (n=14) in the placebo arm. In Part B, mean hemoglobin levels were maintained at >10.5 g/dL. Sustained normalization of mean bilirubin levels was also observed indicating a sustained decrease in hemolysis. Mean hemoglobin level of 11.58 g/dL (range: 6.90-15.30) and 1.01 mg/dL (range: 0.29–5.54) for bilirubin was observed at the last on-treatment visit.
After the last dose of ENJAYMO in the study, signs and symptoms of recurrent hemolysis were observed, nine weeks after the last dose in Part B; mean hemoglobin decreased by 2.41 g/dL (SE: 0.373) and mean bilirubin increased by 1.27 mg/dL (SE: 0.182) from the last available values during treatment.
CARDINAL
The efficacy of ENJAYMO was assessed in an open-label, single-arm, 6-month trial in 24 patients (CARDINAL, NCT03347396). Following the completion of the 6-month treatment period (Part A), patients continued to receive ENJAYMO in a long-term safety and durability of response extension phase (Part B) for an additional 24 months following last patient out from Part A. The trial included a 9 week safety follow-up after the last dose of ENJAYMO. Patients with a confirmed diagnosis of CAD based on chronic hemolysis, polyspecific direct antiglobulin test (DAT), monospecific DAT specific for C3d, cold agglutinin titer ≥64 at 4°C, and IgG DAT ≤1+ and a recent blood transfusion in the 6 months prior to enrollment were administered 6.5 g or 7.5 g ENJAYMO (based on body weight) intravenously over approximately 60 minutes on Day 0, Day 7, and every 14 days thereafter. Patients with cold agglutinin syndrome secondary to infection, rheumatologic disease, systemic lupus erythematosus, or overt hematologic malignancy were excluded, whereas patients with a history of or concomitant low-grade lymphoproliferative disease were not excluded. Major baseline characteristics of the trial population are summarized in Table 7. Table 7: Baseline Characteristics of Patients Included in CARDINAL Parameter Statistic ENJAYMO N=24 Age Mean (SD) Range 71.3 55 to 85 years Sex Female n (%) 15 Male 9 Body weight Mean (SD) Range 67.8 40 to 112 kg Hemoglobin Mean (SD), g/dL
Bilirubin (total) N=21 for bilirubin data excluding patients with Gilbert's syndrome. Mean
(SD), mg/dL 3.1 (2.6 × ULN ULN: Upper limit of normal, LDH: Lactate dehydrogenase. ) LDH Mean (SD), U/L 438 Blood transfusion Median number of transfusions (range) Within last 6 months
Within last 12 months 2.0 Efficacy was based on the proportion of
patients who met the following criteria: an increase from baseline in Hgb level ≥2 g/dL or a Hgb level ≥12 g/dL at the treatment assessment time point (mean value from Weeks 23, 25, and 26), no blood transfusion from Week 5 through Week 26, and no treatment for CAD beyond what was permitted per protocol from Week 5 through Week 26. Efficacy of ENJAYMO in patients with CAD is described in Table 8. Table 8: Efficacy Results in Patients with CAD in CARDINAL Part A Study Parameter Statistic ENJAYMO N=24 Responder A responder was defined as a patient with an increase from baseline in Hgb level ≥2 g/dL or a Hgb level ≥12 g/dL at the treatment assessment time point (mean value from Weeks 23, 25, and 26), no blood transfusion from Week 5 through Week 26, and no treatment for CAD beyond what was permitted per protocol from Week 5 through Week 26. n (%) 13 Hemoglobin level ≥12 g/dL or Increase in Hemoglobin level of ≥2 g/dL n (%) 15 Hemoglobin level ≥12 g/dL n (%) 9 Increase in Hemoglobin level of ≥2 g/dL n (%) 15 Patients not receiving RBC transfusion from Week 5 through Week 26 (transfusion avoidance) n (%) 17 Patients not receiving protocol-prohibited CAD medications Prohibited therapies included rituximab alone or in combination with cytotoxic agents. from Week 5 through Week 26 n (%) 22 In Part A, among 14 patients with baseline and follow-up bilirubin values, the mean was 3.23 mg/dL (2.7-fold ULN) at baseline and 0.91 mg/dL (0.8-fold ULN) at the treatment assessment time point. The least-squares (LS) mean change was reduction of -2.23 mg/dL (95% CI: -2.49 to -1.98). Among 17 patients with baseline and follow-up LDH values, the mean LDH was 424 U/L (1.7-fold ULN) at baseline and 301 U/L (1.2-fold ULN) at the follow-up time point. The least squared mean change in LDH at the treatment assessment time point was reduction of -126 (95% CI: -218 to -35). In CARDINAL, an increase in mean hemoglobin level of 2.29 g/dL (SE: 0.308) was observed at Week 3 and 3.18 g/dL (SE: 0.476) at treatment assessment time point.
The observed model mean change in hemoglobin level from baseline at treatment assessment time point was an improvement of 2.60 g/dL (95% CI: 0.74, 4.46). In Part B, mean hemoglobin levels were maintained at >10 g/dL. Sustained normalization of mean bilirubin levels was also observed indicating a sustained decrease in hemolysis. Mean hemoglobin level of 12.23 g/dL (range: 9.20–14.40) and 0.96 mg/dL (range: 0.4–1.7) for bilirubin was observed at the last on-treatment visit. After the last dose of ENJAYMO in the study, signs and symptoms of recurrent hemolysis were observed, nine weeks after the last dose in Part B; mean hemoglobin decreased by 2.28 g/dL (SE: 0.402) and mean bilirubin increased by 1.42 mg/dL (SE: 0.192) from the last available values during treatment.
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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