Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Sebelipase Alfa · 4 trials · 4 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 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).
The primary efficacy endpoint was the percentage of participants (%) in the PES who survived to at least 12 months of age.
| 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. |
| 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. |
| Open-Label Sebelipase Alfa | EXPERIMENTAL | Participants were administered sebelipase alfa once weekly (qw) as an intravenous (IV) infusion at the same dose received in Study LAL-CL01 (0.35, 1, or 3 milligrams per kilogram \[mg/kg\]) for 4 weeks. After the initial 4 qw doses, participants transitioned to dosing every other week (qow) at either 1 mg/kg (participants who initiated treatment at 0.35 or 1 mg/kg qw) or 3 mg/kg (participants who initiated dosing at 3 mg/kg qw). Subsequent modifications to the dose and dosing frequency were permitted for individual participants based on observed safety, tolerability, and clinical response to treatment. Participants could continue to receive treatment with sebelipase alfa for up to 5 years. |
| 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. |
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 an investigational enzyme replacement therapy being developed for lysosomal acid lipase deficiency, a rare genetic condition. It is studied in patients with cholesterol ester storage disease (CESD), Wolman disease, and related forms of LAL deficiency. The drug is administered to address the underlying enzyme deficiency in these conditions.
Sebelipase Alfa is developed by AstraZeneca PLC, which trades under the ticker AZN. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with lysosomal acid lipase deficiency, including those with cholesterol ester storage disease.
Sebelipase Alfa has completed Phase 3 clinical development. The pivotal Phase 3 trial, known as ARISE (NCT01757184), enrolled 66 participants with lysosomal acid lipase deficiency. The drug remains investigational and is not yet approved by regulatory authorities.
Sebelipase Alfa has completed four clinical trials. These include a Phase 1 study (NCT01307098) in adults, a Phase 2 study (NCT01371825) in children with growth failure, the Phase 3 ARISE trial (NCT01757184), and a Phase 2 study (NCT02112994) in patients as young as 8 months.
Sebelipase Alfa is designed to replace the deficient lysosomal acid lipase enzyme in patients with LAL deficiency. By providing the missing enzyme, the drug aims to restore the breakdown of cholesteryl esters and triglycerides within lysosomes, addressing the underlying metabolic defect in conditions like cholesterol ester storage disease.
Yes, Sebelipase Alfa was previously known as SBC-102. The Phase 1 clinical trial NCT01307098 used the SBC-102 designation in its title, confirming that both names refer to the same investigational drug for lysosomal acid lipase deficiency.