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Approved nov 30 2012
A SLAMF7-directed immunostimulatory antibody used to treat multiple myeloma.
Elotuzumab (brand name Empliciti, previously known as HuLuc63) is a humanized monoclonal antibody used in relapsed multiple myeloma. The package insert denotes its mechanism as a SLAMF7-directed (also known as CD 319) immunostimulatory antibody.
Approvals and indications
In May 2014, it was granted “Breakthrough Therapy” designation by the FDA.  On November 30, 2015, FDA approved elotuzumab as a treatment for patients with multiple myeloma who have received one to three prior medications. Elotuzumab was labeled for use with lenalidomide and dexamethasone. Each intravenous injection of elotuzumab should be premedicated with dexamethasone, diphenhydramine, ranitidine and acetaminophen.
Elotuzumab is APPROVED for safety and efficacy in combination with lenalidomide and dexamethasone.
Monoclonal antibody therapy for multiple myeloma, a malignancy of plasma cells, was not very clinically efficacious until the development of cell surface glycoprotein CS1 targeting humanized immunoglobulin G1 monoclonal antibody – Elotuzumab. Elotuzumab is currently APPROVED in relapsed multiple myeloma.
Elotuzumab (HuLuc63) binds to CS1 antigens, highly expressed by multiple myeloma cells but minimally present on normal cells. The binding of elotuzumab to CS1 triggers antibody dependent cellular cytotoxicity in tumor cells expressing CS1. CS1 is a cell surface glycoprotein that belongs to the CD2 subset of immunoglobulin superfamily (IgSF). Preclinical studies showed that elotuzumab initiates cell lysis at high rates. The action of elotuzumab was found to be enhanced when multiple myeloma cells were pretreated with sub-therapeutic doses of lenalidomide and bortezomib. The impressive preclinical findings prompted investigation and analysis of elotuzumab in phase I and phase II studies in combination with lenalidomide and bortezomib.
Elotuzumab As Part of Combination Therapy: Clinical Trial Results
Elotuzumab showed manageable side effect profile and was well tolerated in a population of relapsed/refractory multiple myeloma patients, when treated with intravenous elotuzumab as single agent therapy. Lets’ take a look at how elotuzumab fared in combination therapy trials,
In phase I trial of elotuzumab in combination with Velcade/bortezomib in patients with relapsed/refractory myeloma, the overall response rate was 48% and activity was observed in patients whose disease had stopped responding to Velcade previously. The trial results found that elotuzumab enhanced Velcade activity.
A phase I/II trial in combination with lenalidomide and dexamethasone in refractory/relapsed multiple myeloma patients showed that 82% of patients responded to treatment with a partial response or better and 12% of patients showed complete response. Patients who had received only one prior therapy showed 91% response rate with elotuzumab in combination with lenalidomide and dexamethasone.
Phase I/II trials of the antibody drug has been very impressive and the drug is currently into Phase III trials. Two phase III trials are investigating whether addition of elotuzumab with Revlimid and low dose dexamethasone would increase the time to disease progression. Another phase III trial (ELOQUENT 2) is investigating and comparing safety and efficacy of lenalidomide plus low dose dexamethasone with or without 10mg/kg of elotuzumab in patients with relapsed/refractory multiple myeloma.
Elotuzumab is being investigated in many other trials too. It is being evaluated in combination with Revlimid and low-dose dexamethasone in multiple myeloma patients with various levels of kidney functions, while another phase II study is investigating elotuzumab’s efficacy in patients with high-risk smoldering myeloma.
The main target of multiple myeloma drug development is to satisfy the unmet need for drugs that would improve survival rates. Elotuzumab is an example that mandates much interest in this area and should be followed with diligence.
Empliciti will be sold in the U.S. in two vials sizes: A smaller vial that contains 300 mg of the drug, and a larger vial that contains 400 mg.
Bristol-Myers Squibb has informed The Beacon that the wholesale price per vial of Empliciti will be $1,776 for the 300 mg vial and $2,368 for the 400 mg vial.
Using these prices and an assumed patient weight of between 154 and 176 pounds, Empliciti will cost $18,944 per four-week cycle for each of the first two cycles of treatment, and $9,472 per cycle thereafter. This means, in turn, that Empliciti’s cost per year will be $142,080 in the first year and $123,136 in subsequent years.
In comparison, Velcade costs between $4,800 and $8,500 per four-week cycle, depending on how often it is dosed. Ninlaro costs $8,670 per four-week cycle. And Kyprolis costs $10,500 per four-week cycle at the standard (20 – 27 mg/m2) dose.
Additional details about the FDA approval of Empliciti can be found in this press release from the FDA, a related press release from Bristol-Myers Squibb and AbbVie, and the full Empliciti prescribing information.
The results of the ELOQUENT-2 trial were published in Lonial, S. et al., “Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma,” The New England Journal of Medicine, June 2, 2015 (abstract). Slides from the ASCO presentation summarizing the ELOQUENT-2 results can be viewed here (PDF, courtesy of Dr. Lonial). This Beacon news article provides an in-depth look at the trial results.
|Molecular mass||145.5 kDa|
1 “Press Announcement—FDA approves Empliciti, a new immune-stimulating therapy to treat multiple myeloma”. U.S. Food and Drug Administration. Retrieved 3 December 2015.
2“Empliciti (elotuzumab) for Injection, for Intravenous Use. Full Prescribing Information” (PDF). Empliciti (elotuzumab) for US Healthcare Professionals. Bristol-Myers Squibb Company, Princeton, NJ 08543 USA.
3 “Bristol-Myers Squibb and AbbVie Receive U.S. FDA Breakthrough Therapy Designation for Elotuzumab, an Investigational Humanized Monoclonal Antibody for Multiple Myeloma” (Press release). Princeton, NJ & North Chicago, IL: Bristol-Myers Squibb. 2014-05-19. Retrieved 2015-02-05.