- |||||||||| zetomipzomib (KZR-616) / Kezar
Enrollment change, Trial completion date, Trial termination, Trial primary completion date: A Study of Zetomipzomib (KZR-616) in Patients with Active Lupus Nephritis (PALIZADE) (clinicaltrials.gov) - Nov 19, 2024 P2, N=84, Terminated, N=279 --> 84 | Trial completion date: Jul 2026 --> Nov 2024 | Suspended --> Terminated | Trial primary completion date: May 2026 --> Nov 2024; Sponsor Decision.
- |||||||||| zetomipzomib (KZR-616) / Kezar
Trial completion date, Trial initiation date: A Study of Zetomipzomib (KZR-616) in Patients With Autoimmune Hepatitis (PORTOLA) (clinicaltrials.gov) - Apr 11, 2023 P2a, N=24, Recruiting, These results further support the potential activity of zetomipzomib in hard-to-treat LN patients. Trial completion date: Sep 2024 --> Mar 2025 | Initiation date: Jan 2023 --> Apr 2023
- |||||||||| zetomipzomib (KZR-616) / Kezar
Impact of Immunoproteasome Inhibition in Preclinical Studies of Hemophagocytic Lymphohistiocytosis (ENMCC - 295-296) - Nov 4, 2022 - Abstract #ASH2022ASH_1300; The anti-inflammatory effect of immunoproteasome inhibition in our model of pHLH is summarized in the Figure, whereby KZR-616 is proposed to decrease presentation of LCMV antigens leading to less T cell activation, proliferation and IFNg production. The lack of impact on TNF production might explain why some disease manifestations are not improved in these studies.
- |||||||||| ONX 0914 / Protalex, zetomipzomib (KZR-616) / Kezar
Preclinical, Journal: Effective therapy of polymyositis in mice via selective inhibition of the immunoproteasome. (Pubmed Central) - Sep 10, 2022 In conclusion, selective inhibition of the immunoproteasome displays therapeutic efficacy in a pre-clinical mouse model of PM with suppression of muscle inflammation and preservation of muscle strength. Positive results from this study support the rationale for using KZR-616 in clinical studies.
- |||||||||| Clinical, Review, Journal: Current and new targets for treating myositis. (Pubmed Central) - Jul 28, 2022
Further studies are needed to assess the role of newer therapies such as abatacept (inhibition of T cell co-stimulation), sifalimumab (anti-IFNα), Janus kinase [JAK] inhibitors, apremilast (phosphodiesterase 4 inhibitor), and KZR-616 (selective inhibitor of the immunoproteasome) given their biological plausibility and encouraging recent small-case series results. The future of IIM therapy will depend on exploring biomarkers implicated in the etiopathogenesis of IIM, improvements in myositis classification based on serological and histopathological features, and well-designed controlled clinical trials using validated consensus outcome measures.
- |||||||||| zetomipzomib (KZR-616) / Kezar
Trial completion date, Trial primary completion date: MISSION: A Study of KZR-616 in Patients With SLE With and Without Lupus Nephritis (clinicaltrials.gov) - Mar 14, 2022 P1b/2, N=68, Active, not recruiting, The study also demonstrates a robust source of in vitro metabolism identification that correlated very well with in vivo PK metabolism for peptide epoxyketones. Trial completion date: Jun 2022 --> Aug 2022 | Trial primary completion date: Jan 2022 --> Aug 2022
- |||||||||| KZR-616 / Kezar
Clinical, Review, Journal: Discovery and Early Clinical Development of Selective Immunoproteasome Inhibitors. (Pubmed Central) - Feb 25, 2022 The discovery that selective inhibitors of the immunoproteasome possess broad anti-inflammatory activity in preclinical models has led to the progression of multiple compounds to clinical trials. This review focuses on the anti-inflammatory potential of immunoproteasome inhibition and the early development of KZR-616, the first selective inhibitor of the immunoproteasome to reach clinical testing.
- |||||||||| zetomipzomib (KZR-616) / Kezar
Enrollment closed: MISSION: A Study of KZR-616 in Patients With SLE With and Without Lupus Nephritis (clinicaltrials.gov) - Jan 19, 2022 P1b/2, N=68, Active, not recruiting, This review focuses on the anti-inflammatory potential of immunoproteasome inhibition and the early development of KZR-616, the first selective inhibitor of the immunoproteasome to reach clinical testing. Recruiting --> Active, not recruiting
- |||||||||| Ninlaro (ixazomib) / Takeda, KZR-616 / Kezar
PK/PD data, Review, Journal: Proteasome Inhibitors and Their Pharmacokinetics, Pharmacodynamics, and Metabolism. (Pubmed Central) - Dec 30, 2021 Here, we compare and contrast the pharmacokinetics (PK), pharmacodynamics (PD), and metabolism of these 2 classes of compounds in preclinical models and clinical studies. The distinct metabolism of peptide epoxyketones, which is primarily mediated by microsomal epoxide hydrolase, is highlighted and postulated as a favorable property for the development of this class of compound in chronic conditions.
- |||||||||| KZR-616 / Kezar
Review, Journal: A Nut for Every Bolt: Subunit-Selective Inhibitors of the Immunoproteasome and Their Therapeutic Potential. (Pubmed Central) - Dec 16, 2021 These promising findings led to the identification of natural and synthetic iCP inhibitors with distinct chemical structures, varying potency and subunit selectivity. This review presents the most prominent iCP inhibitors with respect to possible scientific and medicinal applications, and discloses recent trends towards pan-immunoproteasome reactive inhibitors that cumulated in phase II clinical trials of the lead compound KZR-616 for chronic inflammations.
- |||||||||| Journal: Research progress in proteasome inhibitor resistance to multiple myeloma. (Pubmed Central) - Sep 28, 2021
However, the drug resistance of PIs in MM is still a problem. The mechanisms for PIs resistance to MM include ubiquitin-proteasome pathway, autophagy lysosome pathway, endoplasmic reticulum stress pathway, cell survival signal pathway, exosome-mediated resistance, and bone marrow microenvironment-mediated resistance.
- |||||||||| zetomipzomib (KZR-616) / Kezar
Enrollment closed: PRESIDIO: A Phase 2 Study of KZR-616 to Evaluate Safety and Efficacy in Patients With Active Polymyositis or Dermatomyositis (clinicaltrials.gov) - Aug 24, 2021 P2, N=24, Active, not recruiting, The mechanisms for PIs resistance to MM include ubiquitin-proteasome pathway, autophagy lysosome pathway, endoplasmic reticulum stress pathway, cell survival signal pathway, exosome-mediated resistance, and bone marrow microenvironment-mediated resistance. Recruiting --> Active, not recruiting
- |||||||||| Orencia (abatacept) / BMS
Clinical, Journal: Clinical trials and novel therapeutics in Dermatomyositis. (Pubmed Central) - Feb 4, 2021 At the forefront of these are immunoglobulin, Lenabasum, and Abatacept for which phase III clinical trials are ongoing. In addition, promising clinical studies are ongoing or reported for KZR-616, anti-B cell therapy, anti-interferon drugs, and Repository Corticotrophin Injection (RCI).
- |||||||||| Review, Journal: Proteasome Inhibitors: Harnessing Proteostasis to Combat Disease. (Pubmed Central) - Nov 19, 2020
However, the constant development of new applications for proteasome inhibitors and deeper insights into the intricacies of protein homeostasis suggest that proteasome inhibitors might have novel therapeutic applications. Herein, we summarize the latest advances in proteasome inhibitor development and discuss the future of proteasome inhibitors and other proteasome-based therapies in combating human diseases.
- |||||||||| zetomipzomib (KZR-616) / Kezar
Enrollment change, Trial completion date, Trial primary completion date: MISSION: A Study of KZR-616 in Patients With SLE With and Without Lupus Nephritis (clinicaltrials.gov) - Nov 16, 2020 P1b/2, N=68, Recruiting, Trial completion date: Jun 2021 --> Apr 2022 | Trial primary completion date: Dec 2020 --> Feb 2022 N=124 --> 68 | Trial completion date: Sep 2021 --> Jun 2022 | Trial primary completion date: Jun 2021 --> Jan 2022
- |||||||||| KZR-616 / Kezar, Amgen
[VIRTUAL] KZR-616, a First-in-class Selective Inhibitor of the Immunoproteasome, Ameliorates Polymyositis in a Murine Model () - Oct 8, 2020 - Abstract #ACRARHP2020ACR_ARHP_2624; P2 Selective immunoproteasome inhibition shows therapeutic efficacy in a preclinical mouse model of PM with suppression of muscle inflammation and prevention of muscle weakness. These results strengthen the hypothesis that KZR-616, currently under evaluation in PRESIDIO (KZR-616-003, NCT: NCT04033926), a Phase 2 placebo-controlled, cross-over study of KZR-616 for patients with PM and DM evaluating safety, tolerability, and exploratory efficacy such as muscle function and disease activity over a 32 week treatment period, will elicit similar results.
- |||||||||| zetomipzomib (KZR-616) / Kezar
Enrollment change, Trial completion date, Trial withdrawal, Trial primary completion date: A Phase 2 Study to Evaluate the Safety and Efficacy of KZR-616 in Patients With AIHA and ITP (clinicaltrials.gov) - Aug 7, 2020 P2, N=0, Withdrawn, KZR-616 demonstrated early signals of efficacy as evidenced by improvement in multiple disease activity and serologic markers, including reduction in proteinuria in 2 of 2 patients with LN. N=40 --> 0 | Trial completion date: Jun 2021 --> Aug 2020 | Recruiting --> Withdrawn | Trial primary completion date: Dec 2020 --> Aug 2020
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