FDA Grants ODD to Rhenium-186 Obisbemeda for Pediatric Malignant Glioma

The FDA has granted orphan drug designation to rhenium-186 obisbemeda (Reyobiq; 186RNL) for the treatment of patients with pediatric malignant gliomas, according to a news release from Plus Therapeutics.¹ The designation encompasses a broader scope than initially requested, including pediatric ependymoma, a rare and aggressive form of brain cancer. 186RNL is a highly targeted radiotherapeutic that utilizes nanoliposome technology to deliver high-dose, beta-emitting radiation directly to central nervous system (CNS) tumors.

The designation comes in the wake of several advancements for 186RNL across various disease states. Among them is completion of a Type B meeting with the FDA supporting plans for development in leptomeningeal metastases, positive clinical data from the phase 1 ReSPECT-LM trial (NCT07098806), and advancement of phase 1 and phase 2 studies. Furthermore, the FDA has cleared an investigational new drug application for 186RNL in pediatric patients with high-grade glioma and ependymoma.

“Receiving orphan drug designation for [186RNL] in pediatric malignant gliomas, including the broader scope for progressive pediatric ependymoma, is an important milestone and further validates our approach to delivering targeted radiotherapy directly to CNS tumors,” stated Marc Hedrick, MD, president and chief executive officer of Plus Therapeutics, in the press release.¹ “We believe [186RNL’s] ability to deliver high-dose radiation precisely to tumor sites while minimizing exposure to healthy brain tissue has the potential to meaningfully improve outcomes in this underserved patient population. This orphan designation reinforces the potential applicability of [186RNL] across a wider range of CNS tumor indications and our continued advancement of [186RNL] across multiple CNS cancer indications.”

With regards to the agent’s development in pediatric malignant glioma, the phase 1 ReSPECT-PBC trial (NCT07061626) is a multicenter, open-label study evaluating the safety, tolerability, and preliminary efficacy of 186RNL in pediatric patients with recurrent or progressive malignant brain tumors.^2,3

How is the ReSPECT-PBC trial for pediatric brain cancer designed?

The ReSPECT-PBC trial is structured into 2 parts, beginning with a phase 1, dose-escalation portion to determine the maximum tolerated dose (MTD) of 186RNL in this patient population. Phase 1 will also include 2 cohorts of patients: cohort A, which will enroll up to 6 patients with a tumor size with a maximum diameter of 2 cm and a maximum volume of 4.2 mL, and cohort B, which will enroll up to 6 patients with a tumor size with a maximum diameter of 3.5 cm and a maximum volume of 22.4 mL. Additionally, in cohort A, the concentration of 186RNL will be 0.5 mCI/mL, with a corresponding estimated absorbed dose of approximately 87.5 Gy, compared with 1.0 mCi/mL and approximately 176 Gy in cohort B, respectively. Phase 2 of the trial will use the recommended dose to look at preliminary efficacy in these patients.

The treatment regimen involves a single administration of 186RNL via convection enhanced delivery, a technique that uses a pressure gradient to distribute the radiopharmaceutical directly into the tumor interstitial space. Eligible patients for the study were between 6 and 21 years of age with histologically confirmed malignant high-grade glioma that is recurrent, refractory, or progressive ependymoma or high-grade glioma not eligible for resection or standard care. Patients are required to have a Karnofsky performance status of at least 60, adequate organ function, and a minimum life expectancy of at least 2 months.

Exclusion criteria included spinal disease, infratentorial location of tumor, and involvement of the leptomeninges, among others.

The primary end points of the trial were MTD, overall response rate by Radiographic Assessment in Neuro-Oncology in ependymoma criteria, and progression-free survival at 12 months in high-grade glioma. Secondary end points included safety of 186RNL dose, dose distribution, and neuropsychologic outcome.

References

1. Plus Therapeutics granted U.S. FDA orphan drug designation to REYOBIQ™ in pediatric malignant gliomas. News release. Plus Therapeutics, Inc. April 8, 2026. Accessed April 9, 2026. https://tinyurl.com/4uxn43rj
2. Pediatric brain cancer clinical trial - ReSPECT-PBC. Plus Therapeutics, Inc. Accessed April 9, 2026. https://tinyurl.com/32f8n2au
3. Determine maximum tolerated dose, safety, and tolerability of Rhenium (186Re) in pediatric recurrent, refractory or progressive ependymoma and high-grade glioma. ClinicalTrials.gov. Updated July 11, 2025. Accessed April 9, 2026. https://tinyurl.com/47tbsb3w