Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as KZR-616, KZR-616 Lyophile
zetomipzomib · 4 trials · 5 indications
The number of patients who achieve complete biochemical response (CR), defined as normal ALT, AST, and IgG values (if IgG level is elevated at Baseline) with glucocorticoid dose not higher than starting dose (at Baseline), by Week 24 of the Double-Blind Treatment Period. Analyses were also conducted at Week 12, Week 16, and Week 20.
Proportion of participants who experience AEs (adverse events) and SAEs (serious adverse events) during the double-blind treatment period (DBTP) and the open-label extension (OLE).
Proportion of participants experiencing a disease flare among the participants who achieved a complete biochemical response (CR) during the double-blind treatment period.
The mean Total Improvement Score (TIS) at OLE Week 48, which ranges from 0 to 100 \[low of 0 to high of 100, where higher scores are better\]. The timeframe of 48 weeks was selected because it represented the maximum timeframe of dosing for the last patient enrolled as the study drug administration ended when the last patient enrolled completed 48 weeks of dosing.
The primary efficacy endpoint was mean change from start to end of zetomipzomib (KZR-616) Treatment Periods in the Total Improvement Score (TIS), which ranges from 0 to 100 \[low of 0 to high of 100, where higher scores are better\]. Mean change in TIS was calculated by comparing the Baseline and post Baseline observations for patients in both KZR-616 treatment periods combined. Note: TIS scores for placebo treatment periods are presented in this outcome measure but were not included in the primary outcome measure analysis.
The safety and tolerability of zetomipzomib (KZR-616) when administered as a subcutaneous injection weekly for 13 weeks in adult patients with systemic lupus erythematous (SLE) with and without nephritis, as assessed by number of patients who experienced at least one treatment-related treatment-emergent adverse event. For additional information about the safety and tolerability of KZR-616, please reference the adverse events section of this posting.
To assess the number of patients with lupus nephritis with a 50% reduction in UPCR after 24 weeks of weekly SC injections with KZR-616 when compared to baseline.
| Arm | Type | Description |
|---|---|---|
| zetomipzomib + standard-of-care (glucocorticoids) | EXPERIMENTAL | Initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period. |
| placebo + standard-of-care (glucocorticoids) | PLACEBO_COMPARATOR | Initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period. |
| zetomipzomib + standard-of care (glucocorticoids) open-label extension period | EXPERIMENTAL | Initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment. |
| KZR-616 45 mg + standard therapy (open-label) | EXPERIMENTAL | All patients received a SC injection of 30 mg KZR-616 at Visit 1 (Day 1), followed by weekly SC injections of 45 mg KZR-616 up to a maximum of 96 weeks. Study drug administration ended for all patients in Study KZR-616-003E when the last patient enrolled completed 48 weeks of dosing. |
| Arm A | OTHER | * Treatment Period 1: KZR-616 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks * Treatment Period 2: Placebo SC weekly for 16 weeks |
| Arm B | OTHER | * Treatment Period 1: Placebo SC weekly for 16 weeks * Treatment Period 2: KZR-616 30 mg SC weekly for 2 weeks, then 45 mg SC weekly for 14 weeks |
| KZR-616 45 mg + standard of care therapy (Phase 1b) | EXPERIMENTAL | Dose escalation cohort of patients with SLE with and without nephritis to receive 45 mg dose level of KZR-616 in combination with standard of care therapy. Two Phase 1b cohorts received 45 mg at some point during the study. Cohort 1 received 45 mg zetomipzomib frozen maleate weekly for 13 weeks. Cohort 2a followed a step-up dosing procedure. Patients received zetomipzomib frozen maleate, 30 mg weekly for 2 weeks, followed by 45 mg weekly for 2 weeks then followed by 60 mg weekly for 9 weeks. KZR-616 was administered as a SC injection. |
| KZR-616 60 mg + standard of care therapy (Phase 1b) | EXPERIMENTAL | Dose escalation cohort of patients with SLE with and without nephritis to receive 60 mg dose level of KZR-616 in combination with standard of care therapy. Four Phase 1b cohorts received 60 mg at some point during the study. Cohort 2 received 60 mg zetomipzomib frozen maleate weekly for 13 weeks. Cohorts 2a, 2b, and 2c all followed a step-up dosing procedure. Patients in Cohort 2a received zetomipzomib frozen maleate, 30 mg weekly for 2 weeks, followed by 45 mg weekly for 2 weeks then followed by 60 mg weekly for 9 weeks. Patients in Cohort 2b received zetomipzomib lyophile, 30 mg weekly for 1 week, followed by 60 mg weekly for 12 weeks. Patients in Cohort 2c (tolerability strategies cohort) received zetomipzomib lyophile, 30 mg weekly for 1 week, followed by 60 mg weekly for 12 weeks. KZR-616 was administered as a SC injection. |
| KZR-616 75 mg + standard of care therapy (Phase 1b) | EXPERIMENTAL | Dose escalation cohort of patients with SLE with and without nephritis to receive 75 mg dose level of KZR-616 in combination with standard of care therapy. One Phase 1b cohort received 75 mg at some point during the study. Cohort 3 followed a step-up dosing procedure. Patients in Cohort 3 received zetomipzomib lyophile, 30 mg weekly for 1 week, followed by 75 mg weekly for 12 weeks. KZR-616 was administered as a SC injection. |
| KZR-616 60 mg + standard therapy (Phase 2) | EXPERIMENTAL | 60 mg dose level of KZR-616 selected based on data from the phase 1b dose escalation and administered to patients with active lupus nephritis in combination with standard therapy including at least one immunosuppressive agent. KZR-616 was administered as a SC injection weekly at a dose of 60 mg for 24 weeks (including a step-up from an initial Week 1 dose of 30 mg). \*\* See Limitations/Caveats for additional information |
| Name | Type | Description |
|---|---|---|
| zetomipzomib | DRUG | Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly |
| placebo | DRUG | Subcutaneous injection of placebo |
| zetomipzomib in open-label extension | DRUG | Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly |
| KZR-616 | DRUG | Subcutaneous 30 mg for 1 week, then 45 mg weekly |
Key Inclusion Criteria for the Double-blind Treatment Period: * Must be aged ≥18 years. * Must have a clinical diagnosis of AIH and signs of active disease despite standard-of-care therapy for ≥3 months or disease flare after experiencing complete remission induced by standard-of-care treatment,...
Zetomipzomib is an investigational small molecule developed by Kezar Life Sciences, Inc. (ticker KZR) for autoimmune hepatitis, an immune-mediated liver disease. It is a Phase 2 candidate and has not been approved by the FDA. It belongs to the -zomib class of proteasome-targeting compounds.
Zetomipzomib is being studied as a treatment for autoimmune hepatitis, a condition in which the immune system attacks liver cells. Its development is focused on this immunology indication. The program remains investigational, and the drug is not approved for any use.
Zetomipzomib targets the proteasome, the cellular complex that degrades proteins. It is a small molecule in the -zomib class, a group of compounds that act on proteasome activity. This mechanism is being evaluated in autoimmune hepatitis, where immunoproteasome modulation may affect inflammatory pathways.
Zetomipzomib is made by Kezar Life Sciences, Inc., a biotechnology company that trades under the ticker KZR. Kezar is the developer responsible for the clinical program evaluating the drug in autoimmune hepatitis.
Zetomipzomib is in Phase 2 development. It is an investigational drug and is not FDA approved. The clinical program in autoimmune hepatitis consists of one completed Phase 2 trial, with no trials currently listed as active.
Zetomipzomib has been evaluated in the PORTOLA study, registered as NCT05569759, a Phase 2 trial in patients with autoimmune hepatitis. The trial was completed, enrolled 24 participants, and was randomized, double-blind, and placebo-controlled. It was conducted in the United States in adults aged 18 years and older.