The US Food and Drug Administration (FDA) has granted orphan designation for the drug CB-5083 to treat multiple myeloma (MM).
CB-5083 works by inhibiting p97, an enzyme that controls various aspects of protein homeostasis.
Inhibiting p97 function in cancers has been shown to generate irresolvable endoplasmic reticulum stress that induces a lethal unfolded protein response, which leads to apoptosis and antitumor activity.
CB-5083 has exhibited anticancer activity in preclinical research, and the drug is currently under investigation in two phase 1 studies—one in MM and one in solid tumor malignancies.
Research in MM
Preclinical research presented at ASH 2014 showed that CB-5083 inhibits MM cell viability in vitro. The drug also inhibited tumor growth in xenograft models of MM and in an orthometastatic model of MM.
In addition, CB-5083 demonstrated synergy with carfilzomib, bortezomib, and combination lenalidomide-dexamethasone.
CB-5083 is now under investigation in a phase 1 dose-escalation/dose-expansion trial of MM patients.
Researchers are evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of the drug in patients who have relapsed/refractory or refractory MM after receiving 2 or more lines of therapy, including an immunomodulatory agent and a proteasome inhibitor.
The goal is to enroll up to 60 patients in this trial at multiple US cancer centers that are part of the Multiple Myeloma Research Consortium. More information about the trial is available at www.clinicaltrials.gov (NCT02223598).
About orphan designation
The FDA grants orphan designation to drugs that are intended to treat diseases or conditions affecting fewer than 200,000 patients in the US. Orphan designation provides the sponsor of a drug with various development incentives.
The orphan designation for CB-5083 provides Cleave Biosciences with opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, 7 years of US marketing exclusivity if the drug is approved, and other benefits.
