Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Deferasirox · 22 trials · 29 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.
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 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 | - |
| 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. |
| ICL670 | EXPERIMENTAL | Evaluate the safety and tolerability of deferasirox 20 mg/kg/day over one year in patients with MDS |
| 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. |
| 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. |
| 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. |
| Rifampicin | 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...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Agios Pharmaceuticals, Inc. | AGIO | 5 | PHASE3 | Mitapivat |
| Bristol-Myers Squibb Company | BMY | 6 | PHASE3 | Luspatercept |
| Vertex Pharmaceuticals Incorporated | VRTX | 3 | PHASE3 | CTX001 |
| Novo Nordisk A/S Sponsored ADR Class B | NVO | 2 | PHASE3 | Etavopivat A, Etavopivat B, Etavopivat C |
| Regeneron Pharmaceuticals, Inc. | REGN | 1 | PHASE2 | REGN7999 |
| ICON Plc | ICLR | 1 | PHASE2 | SP-420 |
| Editas Medicine, Inc. | EDIT | 2 | PHASE1 | EDIT-301 |
| Illumina, Inc. | ILMN | 1 | - | Undisclosed |
Deferasirox is an oral iron chelator used to treat transfusional iron overload in beta-thalassemia and other chronic anemias, including sickle cell disease and myelodysplastic syndromes. It is also studied for cardiac iron overload. The drug binds excess iron in the body, allowing its excretion, thereby reducing iron-related organ damage.
Deferasirox targets iron by binding free and labile plasma iron to form a stable complex that is excreted primarily through the feces. This reduces total body iron stores in patients with transfusional iron overload. It is a small molecule iron chelator, not a conventional molecular target like a receptor or enzyme.
Deferasirox is developed by Novartis AG, a multinational pharmaceutical company headquartered in Basel, Switzerland. Novartis trades on the New York Stock Exchange under the ticker symbol NVS. The drug is also known by the brand name Exjade or Jadenu in some markets.
Deferasirox is in Phase 2 clinical development for myelodysplastic syndromes, according to the trial NCT00940602. However, it has completed Phase 3 trials for beta-thalassemia and transfusional iron overload. The drug is investigational for these indications and not yet approved in the studied settings.
Deferasirox has been studied in several completed trials. NCT00171210 evaluated iron chelation in beta-thalassemia patients with transfusional iron overload. NCT00171821 assessed efficacy and safety in transfusion-dependent iron overload. NCT00940602 is a Phase 2 study in myelodysplastic syndromes. All trials are completed.
Yes, Deferasirox is the same as Exjade, a brand name used by Novartis. It is also marketed as Jadenu in some regions. The generic name is deferasirox, and it is an oral iron chelator used to treat chronic iron overload from blood transfusions.