Oprozomib (ONX-0912) is a next-generation analog of carfilzomib, developed by Amgen to possibly treat multiple myeloma.

Oprozomib has been designated an orphan drug by the U.S. Food and Drug Administration (FDA) for the treatment of another and rare type of blood cancer called Waldenstrom’s macroglobulinemia.

How does oprozomib work?

Oprozomib belongs to a class of treatments known as proteasome inhibitors. Cellular components known as proteasomes are required for the breakdown and recycling of damaged proteins in a cell. The excessive division of cancer cells results in the accumulation of a higher number of damaged proteins. By blocking proteasomes, oprozomib works to prevent the recycling of these proteins, which ultimately kills cancer cells.

Oprozomib is a smaller molecule than carfilzomib and as such is more easily absorbed via the small intestines.

Oprozomib in clinical trials

Pre-clinical animal studies have shown that oprozomib has good anti-tumor activity that is comparable to carfilzomib, and is well-tolerated.

A Phase 1/2 clinical trial (NCT02072863) assessed the maximum tolerated dose (MTD), overall response rate (ORR), and complete response rate (CRR) of oprozomib in combination with Alkeran (melphalan) and prednisone in newly diagnosed multiple myeloma patients ineligible for autologous hematopoietic stem cell transplant (AHSCT). The study, which ended in September 2015, showed that ORR among trial participants was 42.9%, with one patient showing complete response and two achieving partial responses.

Another Phase 1/2 clinical trial (NCT01881789) evaluated the MTD, ORR, and CRR of a combination of oprozomib and dexamethasone administered together with Revlimid (lenalidomide) or oral cyclophosphamide in newly diagnosed multiple myeloma patients. The ORR in this study was found to be 71.4%, with two patients achieving a complete response and about 38% having a greater than partial response. All patients achieved stable disease with no evidence of disease progression; none died during the study’s follow-up period. It concluded in September 2019.

The safety and efficacy of oprozomib in combination with Pomalyst (pomalidomide) and dexamethasone was evaluated in a Phase 1 clinical trial (NCT01999335) in patients with primary refractory or relapsed/refractory multiple myeloma (RRMM). Initial results indicated that this combination is well-tolerated in these people and has “encouraging anti-myeloma activity,” with the most adverse effects being diarrhea and anemia.

The same combination treatment is currently being evaluated in another Phase 1 clinical trial (NCT02939183), called INTREPID-1, in 61 patients with RRMM. This study is expected to finish in December 2020.

A Phase 1/2 clinical trial (NCT01832727) to determine the MTD and ORR of a combination of oprozomib and dexamethasone in 65 RRMM patients was completed in June 2019. Its results are yet to be published.

An open-label Phase 1/2 study (NCT01416428) assessing the safety and efficacy of oprozomib in blood cancers such as multiple myeloma and Waldenstrom’s macroglobulinemia in 210 people ended in August 2019. The results of this study are still awaited.

 

Last updated: Nov. 21, 2019

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Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.