FDA Grants Orphan Drug Designation for Rhenium (186Re) Obisbemeda in Pediatric Brain Cancer

The FDA has granted orphan drug designation (ODD) to rhenium (186Re) obisbemeda (Reyobiq) for the treatment of malignant glioma in pediatric patients.¹ This regulatory milestone also extends to the treatment of pediatric ependymoma, addressing a critical need for novel therapeutic options in rare and aggressive pediatric central nervous system (CNS) malignancies.

“Receiving orphan drug designation for [186Re obisbemeda] 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,” said Marc Hedrick, MD, president and CEO of Plus Therapeutics, in a news release. “We believe [186Re obisbemeda’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 [186Re obisbemeda] across a wider range of CNS tumor indications and our continued advancement of [186Re obisbemeda] across multiple CNS cancer indications.”

Clinical Context and Pediatric CNS Malignancies

Pediatric high-grade gliomas (pHGG) and pediatric ependymomas represent some of the most challenging tumors in pediatric oncology. While relatively rare, they are characterized by rapid progression and a poor prognosis. The current standard of care for these tumors typically involves maximal safe surgical resection followed by external beam radiation therapy (EBRT) and systemic chemotherapy. However, survival rates remain low, with 5-year survival for pHGG often cited at less than 20%.²

The therapeutic window for treating pediatric brain tumors is particularly narrow due to the risk of long-term neurocognitive and endocrine sequelae associated with conventional radiation and systemic agents. The blood-brain barrier further complicates treatment by limiting the intracranial penetration of many cytotoxic therapies.

Pharmacological Profile and Mechanism of Action

186Re obisbemeda is an investigational radiotherapeutic composed of the radionuclide rhenium-186 encapsulated within nanoliposomes. This formulation is designed to deliver highly targeted, high-dose radiation directly to the tumor site while minimizing exposure to surrounding healthy brain tissue.¹

The choice of rhenium-186 is strategically significant for CNS applications. As a dual emitter, it provides both therapeutic and diagnostic capabilities. It emits beta particles with a maximum energy of 1.07 MeV, which have a tissue path length of approximately 2 mm, sufficient for localized tumor destruction with minimal collateral damage. Additionally, its gamma emission (137 keV) allows for real-time scintigraphic imaging, enabling clinicians to confirm drug distribution and perform precise dosimetry.³ The isotope’s physical half-life of approximately 90.6 hours supports a sustained therapeutic effect within the tumor microenvironment.

Direct Delivery via CED and the ReSPECT-PBC Trial

To bypass the blood-brain barrier and ensure optimal intratumoral distribution, 186Re obisbemeda is administered via convection-enhanced delivery (CED). This method utilizes a pressure gradient to drive the therapeutic agent through the interstitial spaces of the brain, allowing for a more uniform and concentrated distribution compared to simple diffusion.⁴

The safety, tolerability, and efficacy of this approach are being evaluated in the ReSPECT-PBC clinical trial (NCT07061626).⁵ This phase 1/2a study is a dose-escalation and -expansion trial enrolling pediatric patients aged 6 to 21 years with supratentorial recurrent, refractory, or progressive HGG or ependymoma. The trial, supported by a $3 million grant from the US Department of Defense, seeks to determine the maximum tolerated dose and the recommended phase 2 dose in the pediatric population.¹

Implications of Orphan Drug Designation

The ODD status granted by the FDA provides significant incentives to support the development of therapies for rare diseases affecting fewer than 200,000 individuals in the United States. These incentives include:

• 7 years of market exclusivity following FDA approval.
• Exemption from Prescription Drug User Fee Act (PDUFA) application fees.
• Tax credits for clinical trial expenses.
• Eligibility for federal grants to support clinical research.⁶

This latest designation for 186Re obisbemeda complements previous FDA designations for the same compound in other indications, including adult recurrent glioblastoma and leptomeningeal metastases secondary to breast and lung cancer.¹

Future Outlook

The advancement of 186Re obisbemeda into pediatric trials reflects a growing trend in neuro-oncology toward precision radiopharmaceuticals. By combining local delivery with short-range radiotherapy, investigators aim to provide a more potent treatment for aggressive, recurrent or refractory pediatric brain cancer while sparing the developing brain from the deleterious effects of systemic toxicity and broad-field radiation.

REFERENCES

1. Plus Therapeutics Granted U.S. FDA Orphan Drug Designation for Rhenium (186Re) Obisbemeda for the Treatment of Pediatric Brain Cancer. News release. Plus Therapeutics. April 8, 2026. Accessed April 8, 2026. https://tinyurl.com/5ffhb3d3

2. Jones C, Karajannis MA, Huang PP, et al. Pediatric high-grade glioma: biologically and clinically distinct from adult tumors. Nat Rev Clin Oncol. 2017;14(6):350-362.

3. Brenner AJ, Phillips WT, Bao A, et al. Convection enhanced delivery of rhenium (186Re) obisbemeda (186RNL) in recurrent glioma: A multicenter, single arm, phase 1 clinical trial. Nat Commun. 2025;16(1):2079.

4. Vogelbaum MA, Aghi MK. Convection-enhanced delivery for the treatment of glioblastoma. Neuro Oncol. 2015;17 Suppl 2(Suppl 2):ii3-ii8.

5. 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 8, 2026. https://clinicaltrials.gov/study/NCT07061626

6. Designating an Orphan Product: Drugs and Biological Products. US FDA. Updated August 12, 2024. Accessed April 8, 2026. https://tinyurl.com/5ckfaxtv