Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication KANUMA ® is indicated for the treatment of patients with a diagnosis of Lysosomal Acid Lipase (LAL) deficiency. KANUMA ® is a hydrolytic lysosomal cholesteryl ester and triacylglycerol-specific enzyme indicated for the treatment of patients with a diagnosis of Lysosomal Acid Lipase (LAL) deficiency. ( 1 ) FDA label
Also known as Sebelipase alfa (SBC-102), SBC-102, Kanuma®
Sebelipase Alfa · 5 trials · 5 indications
Alanine aminotransferase (ALT) normalization was defined as an abnormal baseline value (ALT \> the age- and gender-specific upper limit of normal \[ULN\] provided by the central laboratory performing the assay) that becomes normal (\< ULN). Alanine aminotransferase normalization was evaluated at the end of the Double-blind Period (the last double-blind assessment) and at the end of the Open-label Period (last open-label assessment). Baseline for the Open-label Period was defined relative to the first infusion of sebelipase alfa, which occurred at Week 0 for participants in the sebelipase alfa/sebelipase alfa group and Week 22 for participants in the placebo/sebelipase alfa group. The last open-label assessment varied by participant, depending on whether a participant completed treatment through Week 256 or discontinued prior to this timepoint to transition out of clinical study settings.
The primary efficacy endpoint was the percentage of participants (%) in the PES who survived to at least 12 months of age.
The number of participants experiencing severe TEAEs is presented for participants who received sebelipase alfa in this open-label study. Adverse events (AEs) information was obtained at each scheduled contact with the participant (or participant's parent or legal guardian). An AE was defined as any untoward medical occurrence that did not require a causal relationship with study drug administration. An AE could have been any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug. Pre-existing conditions that worsened in severity during the study were reported as AEs. A summary of all serious and other non-serious AEs regardless of causality is located in the Reported AE module. Severity assessed using Clinical Data Interchange Standards Consortium Study Data Tabulation Model standard terminology v3.1.1. Data presented only according to age group, not dose of study drug received.
Safety and tolerability of sebelipase alfa was primarily assessed by monitoring the number of participants reporting treatment-emergent adverse events (TEAEs), including serious adverse events, and infusion-associated reactions (IARs). The number of participants who discontinued from the study due to a TEAE is also presented. An IAR was defined as any adverse event that occurred during the 2-hour infusion or within 4 hours after the end of the infusion and was assessed by the investigator as at least possibly related to study drug. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. TEAEs that occurred after the first dose administration at Week 1 through the End of Study (EOS) are presented. End of study was 30 days (+ 7 days) after the last dose of study drug (at Week 260).
Safety and tolerability of sebelipase alfa was primarily assessed by monitoring the number of participants reporting treatment-emergent adverse events (TEAEs), including serious adverse events, and infusion-related reactions (IRRs). The number of participants who discontinued from the study due to a TEAE is also presented. An IRR was defined as any adverse event that occurred between the start of the infusion and 4 hours after completion of the infusion and was assessed by the Investigator as at least possibly related to study drug. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
| Arm | Type | Description |
|---|---|---|
| Double-blind Sebelipase Alfa | EXPERIMENTAL | Double-blind Period: IV infusions of sebelipase alfa at a dose of 1 mg/kg administered qow for 20 weeks. |
| Double-blind Placebo | PLACEBO_COMPARATOR | Double-blind Period: IV infusions of matched placebo administered qow for 20 weeks. |
| Open-label Sebelipase Alfa/Sebelipase Alfa | EXPERIMENTAL | Participants who were randomized to receive sebelipase alfa during the Double-blind Period and received sebelipase alfa in the Open-label Period. All participants received sebelipase alfa at a dose of 1 mg/kg qow, irrespective of treatment received in the Double-blind Period. Dose modifications were permitted during the Open-label Period. |
| Open-label Placebo/Sebelipase Alfa | EXPERIMENTAL | Participants who were randomized to receive placebo during the Double-blind Period and received sebelipase alfa in the Open-label Period. All participants received sebelipase alfa at a dose of 1 mg/kg qow, irrespective of treatment received in the Double-blind Period. Dose modifications were permitted during the Open-label Period. |
| Open-Label Sebelipase Alfa | EXPERIMENTAL | Participants received intravenous (IV) infusions of sebelipase alfa during the open-label treatment. Participants initially received 0.35 milligrams (mg)/kilogram (kg) qw and escalated to 1 mg/kg qw after demonstrating acceptable safety and tolerability during at least 2 infusions. One participant initiated treatment under a Temporary Use Authorization prior to enrollment, wherein the participant's dose was gradually escalated from 0.2 to 1 mg/kg over 4 weeks; the participant started the study at this dose. Participants on treatment for 96 weeks and on stable qw dosing for 24 weeks could be switched to an every other week (qow) dosing schedule. In the event of protocol-defined disease progression at any time during treatment, a participant could receive a dose increase from 1 to 3 mg/kg qw and, if necessary, a dose increase to 5 mg/kg qw with Safety Committee approval. Participants dosed qow who met dose-escalation criteria were reverted to qw dosing or escalated to 1 or 3 mg/kg qow. |
| Sebelipase Alfa | EXPERIMENTAL | Pediatric and adult participants initiated IV treatment with sebelipase alfa at a dose of 1 mg/kg qow. Participants were considered for a dose adjustment at the discretion of the Investigator and in consultation with the Sponsor. Dose escalation to 3 mg/kg qow was considered if pre-defined dose-escalation criteria were met. If these criteria continued to be met, a subsequent dose escalation to 3 mg/kg every week (qw) was considered. Dose decreases as low as 0.35 mg/kg qow were permitted based upon evidence of intolerance to sebelipase alfa treatment. Participants who completed the 96-week treatment period were permitted to continue receiving sebelipase alfa in an expanded treatment period for up to 48 weeks, pending local drug availability and study participation status. |
| Sebelipase alfa 0.35 mg/kg | EXPERIMENTAL | Cohort 1: Participants were administered once weekly (qw) infusions of 0.35 mg/kg sebelipase alfa. |
| Sebelipase alfa 1 mg/kg | EXPERIMENTAL | Cohort 2: Participants were administered qw infusions of 1 mg/kg sebelipase alfa. |
| Sebelipase alfa 3 mg/kg | EXPERIMENTAL | Cohort 3: Participants were administered qw infusions of 3 mg/kg sebelipase alfa. |
| Name | Type | Description |
|---|---|---|
| Sebelipase Alfa | DRUG | IV infusions of sebelipase alfa |
| Placebo | DRUG | IV infusions of matched placebo |
| Sebelipase alfa (SBC-102) | DRUG | Sebelipase alfa is a recombinant human lysosomal acid lipase enzyme. The investigational medicinal product is an enzyme replacement therapy intended for treatment of participants with LAL Deficiency. Dosing occurred qw for up to 5 years. |
| Sebelipase alfa 0.35 mg/kg | DRUG | Sebelipase alfa is a recombinant human lysosomal acid lipase. |
| Sebelipase alfa 1 mg/kg | DRUG | Sebelipase alfa is a recombinant human lysosomal acid lipase. |
| Sebelipase alfa 3 mg/kg | DRUG | Sebelipase alfa is a recombinant human lysosomal acid lipase. |
Inclusion Criteria: * Participant and/or participant's parent or legal guardian provided informed consent. * Participant was ≥ 4 years of age on the date of informed consent. * Deficiency of LAL enzyme activity confirmed by dried blood spot testing at screening. * Alanine aminotransferase ≥ 1.5x up...
Sebelipase alfa is used to treat lysosomal acid lipase deficiency, including cholesterol ester storage disease (CESD). It is an enzyme replacement therapy studied in adults and children, including infants with growth failure due to the condition. It is given as a weight-based dose, such as 0.35 mg/kg.
Sebelipase alfa is developed by AstraZeneca PLC, which trades under the ticker AZN. The company sponsored the clinical trial program for the drug in lysosomal acid lipase deficiency, including the ARISE study and a long-term extension study in adults with cholesterol ester storage disease.
Sebelipase alfa has been studied across Phase 2 and Phase 3 clinical trials in lysosomal acid lipase deficiency, and all of its listed trials are completed. The program includes a Phase 3 study (ARISE) and several Phase 2 studies, with no trials currently active.
Sebelipase alfa has been evaluated in completed trials including NCT01757184 (the Phase 3 ARISE study, 66 participants), NCT02112994 (Phase 2, 31 participants), NCT01488097 (a Phase 2 adult extension study, 8 participants), and NCT01371825 (Phase 2/Phase 3 in children with growth failure, 9 participants).
Yes, sebelipase alfa is the same drug as SBC-102. It is also written as sebelipase alfa 0.35 mg/kg when referring to a weight-based dose. These names all refer to the same enzyme replacement therapy developed by AstraZeneca for lysosomal acid lipase deficiency and cholesterol ester storage disease.
Across the four listed sebelipase alfa trials, 114 participants were enrolled in total. Enrollment ranged from 8 participants in the adult long-term extension study to 66 participants in the Phase 3 ARISE trial, with the remaining Phase 2 studies enrolling 31 and 9 participants.