Opaganib Earns FDA Orphan Drug Status in Neuroblastoma

The FDA previously granted orphan drug designation to opaganib as a treatment for patients with cholangiocarcinoma.

The FDA has granted orphan drug designation to opaganib (ABC294640), an investigational SPHK2 selective inhibitor, as a treatment for pediatric patients with neuroblastoma, according to a press release from the developer, RedHill Biopharma Ltd.¹

Investigators hypothesize that the agent’s host-directed action may inhibit multiple pathways, induce autophagy and apoptosis, and disrupt viral replication by simultaneously targeting the sphingolipid-metabolizing enzymes SPHK2, DES1, and GCS. The agent’s mechanism of action has made it a candidate for application across various diseases such as syndromes associated with obesity, prostate cancer, cholangiocarcinoma, gastrointestinal acute radiation syndrome, exposure to Sulfur Mustard, and COVID-19.

According to the press release, the FDA previously granted orphan drug designation to opaganib for cholangiocarcinoma.

“This designation for neuroblastoma—the most common infancy malignancy and for which new options are urgently needed—adds to opaganib's potential as a novel oncological agent,” Mark Levitt, MD, PhD, chief scientific officer at RedHill, said in the press release.¹

“Opaganib has broad oncology potential with promising preliminary clinical data in solid tumor cancers such as prostate cancer and [cholangiocarcinoma], and data from a range of [United States] government supported and Apogee conducted preclinical studies in various indications, including radioprotection, and also in combination with RedHill's RHB-107. We also see such utility extending to the potential for opaganib to have a sensitizing effect in hormone receptor pathway inhibition therapy, which the company expects to test in a planned externally funded phase 2 study,” Levitt added.

Investigators previously assessed treatment with opaganib for patients with cholangiocarcinoma in a phase 2a trial (NCT03377179) and for those with metastatic castration-resistant prostate cancer (CRPC) as part of a phase 2 study (NCT04207255).

Phase 2a Cholangiocarcinoma Trial

Investigators of the single-arm phase 2a trial evaluated opaganib alone and in combination with hydroxychloroquine sulfate for patients with advanced cholangiocarcinoma.² In part 1 of the trial, patients received opaganib at 500 mg twice daily. In part 2, patients received opaganib at 500 mg twice daily in combination with hydroxychloroquine sulfate at a determined level as part of continuous 28-day cycles.

The trial’s primary end points were objective response rate in part 1 and durable disease control rate in part 2. Secondary end points included overall survival, progression-free survival, maximum plasma concentration, treatment-related adverse effects, and quality of life.

Patients 18 years and older with histologically confirmed intrahepatic, perihilar, or extra-hepatic cholangiocarcinoma and no more than 2 prior lines of therapy including systemic anti-neoplastic therapy were eligible for enrollment on the trial. Additional eligibility criteria included having unresectable tumors, 1 or more measurable tumors per RECIST v1.1 guidelines, an ECOG performance status of 0 or 1, and a life expectancy of 3 months or longer.

Phase 2 Metastatic CRPC Trial

In this phase 2 trial, investigators assessed treatment with opaganib for patients with metastatic CRPC following progressive disease on prior therapy with abiraterone (Zytiga) or enzalutamide (Xtandi).³ Across various treatment cohorts, patients were assigned to receive opaganib at 250 mg or 500 mg orally twice a day continuously in combination with enzalutamide or abiraterone intravenously.

The trial’s primary end point was disease control status, defined as the rate of patients with stable disease or better per Prostate Cancer Working Group 3 criteria following 4 treatment cycles.

Patients 18 years and older with metastatic CRPC and documented tissue diagnosis via pathology report; radiographically confirmed metastases; and adenocarcinoma, ductal carcinoma, or a combination of these conditions were able to enroll on the trial. Other requirements for study entry included having an ECOG performance status of 0 to 2 and adequate liver function.

References

1. RedHill's Opaganib granted orphan drug designation by the FDA for childhood cancer, neuroblastoma. News release. RedHill Biopharma Ltd. August 26, 2024. Accessed August 27, 2024. https://tinyurl.com/2n83zxfx
2. A study of ABC294640 (Yeliva ®) alone and in combination with hydroxychloroquine sulfate in treatment of patients with advanced cholangiocarcinoma. ClinicalTrials.gov. Updated April 4, 2023. Accessed August 27, 2024. https://tinyurl.com/45mpmhwe
3. Addition of opaganib to androgen antagonists in patients with mCRPC. ClinicalTrials.gov. Updated June 25, 2024. Accessed August 27, 2024. https://tinyurl.com/wvk6yfre