Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication Exjade is an iron chelator indicated for the treatment of chronic iron overload due to blood transfusions in patients 2 years of age and older. ( 1.1 ) Exjade is indicated for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion-dependent thalassemia (NTDT) syndromes, and with a liver iron (Fe) concentration (LIC) of at least 5 mg Fe per gram of dry weight and a serum… FDA label
Also known as Deferasirox (ICL670), ICL670, ICL670A, chelator, desferal, iron chelation, Exjade
Deferasirox · 25 trials · 30 indications
Numbers represent counts of participants within the categories. An adverse event (AE) was defined as treatment emergent if its onset date is on or after (≥) the first administration of study treatment within this study or events present prior to start of study treatment but increased in severity on or after (≥) the first administration of study treatment within this study but not later than 30 days after the last study treatment in this study
The change from baseline at each time point is calculated only for subjects with a value at baseline and the particular time point. Post = Post baseline, Change = Post - Baseline
The change from baseline at each time point is calculated only for subjects with a value at baseline and the particular time point. Post = Post baseline, Change = Post - Baseline
The change from baseline at each time point is calculated only for subjects with a value at baseline and the particular time point. Post = Post baseline, Change = Post - Baseline
The change from baseline at each time point is calculated only for subjects with a value at baseline and the particular time point. Post = Post baseline, Change = Post - Baseline
The change from baseline at each time point is calculated only for subjects with a value at baseline and the particular time point. Post = Post baseline, Change = Post - Baseline
The change from baseline at each time point is calculated only for subjects with a value at baseline and the particular time point. Post = Post baseline, Change = Post - Baseline
The change from baseline at each time point is calculated only for subjects with a value at baseline and the particular time point. Post = Post baseline, Change = Post - Baseline
Safety as assessed by the number of participants with death, serious adverse events (SAE), and/or Adverse Events (AEs) leading to study drug interruption or discontinuation. Note: only treatment emergent AEs are summarized.
Adverse events results are based on preferred terms with at least 7% of participants in any group.
Cardiac T2\* is the most sensitive and reproducible test in detecting myocardial iron load. A cardiac T2\* value of \<10 ms is defined as severe cardiac iron overload. Participants who do not have baseline T2\* or do not have any post-baseline T2\* are excluded from the analysis.
Event-free survival was defined as the time from the date of randomization to the date of the first documented non-fatal event (worsening cardiac function, hospitalization for congestive heart failure, liver function impairment, liver cirrhosis, transformation to AML, as defined in the protocol), or death, whichever occurred first. Participants who did not experience a non-fatal event as of the time of data cut-off (end of study), as well as participants who did not experience a non-fatal event and stopped study participation before the data cut-off, were censored as specified in the protocol.
Unsatisfactory response is a monthly MRI T2\* improvement lower than 3% versus baseline.
LIC was measured by magnetic resonance imaging technique at baseline and Week 52. Estimates were obtained from an Analysis of Covariance (ANCOVA) model for change in LIC between baseline and Week 52 with treatment as factor and baseline LIC as covariate.
Liver iron concentration was measured at Core Baseline and at the end of the Extension Study. Magnetic Resonance Imaging (MRI) scans were analyzed at a central laboratory to determine the LIC value. The percentage of participants with LIC \< 5 mgFe/g dw (milligram iron/gram dry weight) change from Baseline at the end of the Extension Study is reported.
Liver iron concentration (LIC), a predictor of iron burden, was measured using relaxation rate magnetic resonance imaging (R2-MRI) technique. Relaxation rate was determined as R2 = 1/relaxation time (T2). The baseline value of LIC of participants was categorized as \< 7, ≥ 7 to \< 15, and ≥ 15 milligram of iron/tissue dry weight (mg Fe/g dw). A negative change from baseline favored study treatment in reducing LIC.
Cardiac T2\* was measured in the short axis plane at the widest point of a 4-chamber localizer using custom breath-hold R2\* gradient echo sequences modeled after techniques used by Anderson et al (2001) and Westwood et al (2003).
Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the study, whether or not considered related to the participant's participation in the study. Serious Adverse Events include adverse events that result in either of death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect.
The number of participants with Adverse Events (AEs) overall and according to Medical Dictionary for Regulatory Activities (MedDRA) preferred term greater than or equal to 5% participants in any group by treatment in the first 24 weeks.
Safety as assessed by the number of participants with adverse event or death after the start of ICL670.
Safety was assessed using reports of adverse events of all participants in this study. Serious adverse events are those events that resulted in death, were life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.
Safety parameters were measured by the number and type of adverse events (AEs). An adverse event is any untoward medical occurence in a patient administered a medicinal product that does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign ( for example, an abnormal laboratory finding), symptom or disease temporally associated with the use of the medicinal product, whether or not this is associated with the use of this medicinal product.
Change in Liver Iron Concentration \[LIC\] measured by means of SQUID (Superconducting Quantum Interference Device). LIC is expressed in milligrams of iron per gram of liver dry weight (mg Fe/g dw)
The mean percentage change in liver iron content (LIC) as assessed by superconducting quantum interference device (SQUID) was evaluated by comparing the LIC at the start of Deferasirox treatment to the LIC at the end of the 5 year extension study for participants who were treated with Deferasirox for more than 3.5 years. LIC is expressed in milligrams of iron per gram of liver dry weight (mgFe/g dw). Relative change = 1- (Change in LIC from Baseline/Baseline level) x 100.
Mean absolute change in serum ferritin from baseline to the end of the extension study.
| Arm | Type | Description |
|---|---|---|
| Deferasirox | EXPERIMENTAL | Treatment will be administered daily for up to 24 months. For each patient the daily dose is calculated based on the patient's actual body weight. |
| ICL670 (Deferasirox) | EXPERIMENTAL | - |
| ICL670 | EXPERIMENTAL | - |
| Deferoxamine | ACTIVE_COMPARATOR | - |
| Placebo | PLACEBO_COMPARATOR | 10 mg/kg/day (once daily) for the first 2 weeks of treatment, followed by 20 mg/kg/day (once daily) from Week 2 to End of Treatment. After 3 months of treatment at 20 mg/kg/day, the dose was allowed to be adjusted by 5 or 10 mg/kg/day up to 40 mg/kg/day based on serum ferritin responses. When a target serum ferritin level was reached (usually between 500 and 1000 µg/L), the dose could be reduced by 50% to maintain the serum ferritin within the target range. |
| 5 mg/kg/day deferasirox | EXPERIMENTAL | Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks. |
| 10 mg/kg/day deferasirox | EXPERIMENTAL | Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks. |
| 5 mg/kg/day placebo | PLACEBO_COMPARATOR | Placebo tablet matching 5 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks. |
| 10 mg/kg/day placebo | PLACEBO_COMPARATOR | Placebo tablet matching 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks. |
| deferasirox every day for 77 weeks | EXPERIMENTAL | Participants received Deferasirox 30 milligrams per kilogram per day (mg/kg/day) orally once daily (OD), 30 minutes before breakfast, preferably around the same time every morning if possible. Deferasirox tablets were dropped into water or orange juice, or apple juice and stirred until completely dispersed. For doses less than 1 gram (g), tablets were dissolved in at least 100 milliliter (mL) of liquid; for doses of 1 to 3 g, tablets were dissolved in at least 200 mL. After tablets were fully disintegrated, the liquid was promptly consumed. |
| Deferasirox (ICL670) | EXPERIMENTAL | Deferasirox (ICL670) 20 mg/kg orally once daily for 104 weeks. |
| Deferoxamine (DFO) then ICL670 | EXPERIMENTAL | Deferoxamine (DFO) subcutaneously for a weekly dose of 175 mg/kg for 24 weeks then crossed over to receive Deferasirox (ICL670) orally 20 mg/kg for a total of 104 weeks on therapy. |
| ICL670 + deferoxamine | EXPERIMENTAL | - |
| Deferasirox Crossover | EXPERIMENTAL | Deferasirox Crossover group consists of participants who were initially randomized to 40 mg/kg/day deferoxamine (DFO)subcutaneously in the main study and comparative prolongation study and crossed over to 5mg/kg/day to 30 mg/kg/day deferasirox orally daily at the beginning of the 5-year non-comparative extension study |
| Arm 1 | EXPERIMENTAL | - |
| Mild hepatic impaired | EXPERIMENTAL | - |
| Moderate hepatic impaired | EXPERIMENTAL | - |
| Severe hepatic impaired | EXPERIMENTAL | - |
| Healthy volunteers | EXPERIMENTAL | Controlled group |
| Name | Type | Description |
|---|---|---|
| Deferasirox | DRUG | Deferasirox FCT will be provided as 90 mg, 180 mg and 360 mg film-coated tablets for oral use. |
| ICL670 | DRUG | - |
| deferoxamine | DRUG | - |
| Deferasirox and Deferoxamine | DRUG | - |
| Placebo | DRUG | Inactive ingredients used as a placebo comparator, provided as 125 mg, 250 mg, and 500 mg dispersible tablets for oral use |
| Deferasirox (ICL670) | DRUG | The recommended initial daily dose of Deferasirox is 20 mg/kg body weight. |
| Deferoxamine (DFO) | DRUG | Deferoxamine was supplied in vials of 500 mg and 2000 mg administered subcutaneously for a weekly dose of 175 mg/kg. |
| ICL670, deferoxamine | DRUG | - |
Key Inclusion Criteria for subjects: * Completed 24-weeks of study treatment as described in the core protocol (CICL670F2201). * Were deemed to have tolerated deferasirox treatment by the investigator. * Provided written informed consent/assent before any study-specific procedures were performed. F...
Deferasirox is used to treat chronic iron overload in conditions such as beta thalassemia transfusion dependent, cardiac iron overload, chronic anemia, and myelodysplastic syndromes. It is also studied in patients with hepatic impairment. It is a small molecule iron chelator developed by Novartis AG.
Deferasirox is developed by Novartis AG, which trades under the ticker NVS. Novartis is the sponsor of the clinical trials evaluating Deferasirox in iron overload conditions.
Deferasirox is in Phase 2 clinical development according to the available data, with completed trials in iron overload conditions. It is investigational and not approved for the studied indications based on this dataset.
Deferasirox has been studied in four completed trials: NCT02720536 in chronic iron overload, NCT01254227 in cardiac iron overload, NCT01033747 in liver iron overload, and NCT00940602 in myelodysplastic syndromes. These trials enrolled a total of 1,784 participants.
Deferasirox and Deferoxamine are different iron chelators. Deferasirox is also known as ICL670 and has been studied in combination with Deferoxamine in a Phase 2 trial for severe cardiac iron overload. They are distinct agents, though both are used for iron overload.