FDA Grants Orphan Drug Designation to OPN-6602 for R/R Multiple Myeloma

The FDA has granted orphan drug designation (ODD) to OPN-6602, an oral small molecule inhibitor of the E1A binding protein (EP300) and CREB-binding protein (CBP), for the treatment of patients with relapsed or refractory multiple myeloma.1

The agent, which is currently under evaluation in a phase 1 trial (NCT06433947) in patients with multiple myeloma, previously demonstrated preclinical antitumor activity in mouse xenograft models of the disease.2 Specifically, data presented at the 2024 ASH Annual Meeting demonstrated that 71% of models experienced tumor suppression with OPN-6602 alone and 100% saw tumor regression and sustained duration of response when the agent was combined with mezigdomide, pomalidomide (Pomalyst), and dexamethasone.

Additionally, RNA sequencing of treated tumors revealed that OPN-6602 downregulated key multiple myeloma driver and signature genes, suggesting a potential role in overcoming resistance to standard-of-care therapies.

“We are pleased to have received ODD for OPN-6602 for the treatment of multiple myeloma, a further validation of the drug’s therapeutic potential in patients with this disease who have limited treatment options once they have relapsed,” Gideon Bollag, PhD, chief scientific officer of Opna Bio, stated in a news release.1

Phase 1 Trial Design and Patient Enrollment Criteria

The open-label, phase 1 study is evaluating the safety, tolerability, and pharmacokinetic and pharmacodynamic activity of OPN-6602, as well as its preliminary efficacy in patients with relapsed or refractory multiple myeloma.3 The trial consists of three cohorts: a dose-escalation monotherapy arm, a dose-escalation arm combining OPN-6602 with dexamethasone, and a dose-expansion cohort.

In the combination arm, patients will receive OPN-6602 daily along with dexamethasone at 40 mg on days 1, 8, and 15 of each cycle. Enrollment is ongoing across multiple sites.

The trial is enrolling patients with relapsed or refractory multiple myeloma whose disease has progressed after at least three prior therapies, including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody. Eligible patients must also have adequate organ function and be intolerant to or ineligible for established treatments known to provide clinical benefit.

Exclusion criteria include monoclonal gammopathy of undetermined significance, smoldering myeloma, Waldenström macroglobulinemia, IgM myeloma, active plasma cell leukemia, POEMS syndrome, prior Stevens-Johnson syndrome, and central nervous system involvement. Patients who received radiation or chemotherapy within 2 weeks prior to the first study dose, or allogeneic stem cell transplantation or solid organ transplantation within 12 months of screening are also ineligible. Patients who are on immunosuppressive therapy for active graft-versus-host disease will also be excluded.

Additionally, patients with secondary malignancies will be generally excluded, except for those with certain early-stage or adequately treated cancers. Patients with an ongoing systemic infection requiring parenteral therapy, or those with poorly controlled type 2 diabetes are also ineligible.

The primary outcomes of the study include the number and type of dose-limiting toxicities, treatment-emergent adverse effects, and clinical laboratory test abnormalities.

References

1. Opna Bio receives orphan drug designation for OPN-6602, an oral EP300/CBP bromodomain inhibitor, for multiple myeloma. News release. Opna Bio. February 12, 2025. Accessed February 13, 2025. https://www.businesswire.com/news/home/20250212175926/en
2. Opna Bio announces interim data from phase 1 combination study of OPN-2853 with ruxolitinib in patients with advanced myelofibrosis. News release. Opna Bio. December 9, 2024. Accessed February 13, 2025. https://www.opnabio.com/opna-bio-announces-interim-data-from-phase-1-combination-study-of-opn-2853-with-ruxolitinib-in-patients-with-advanced-myelofibrosis
3. Study to assess safety and tolerability of OPN-6602 in subjects with relapsed and/or refractory multiple myeloma. ClinicalTrials.gov. Updated December 10, 2024. Accessed February 13, 2025. https://clinicaltrials.gov/study/NCT06433947