FDA Grants Orphan Drug Designation to Irinotecan Delivery Implant for High-Grade Glioma

The FDA has granted orphan drug designation (ODD) to a locally delivered formulation of irinotecan (ChemoSeed) for the treatment of malignant glioma. The designation covers all high-grade gliomas (WHO grade III and IV tumors), a scope broader than the original application, which had been limited to glioblastoma (GBM) alone.¹

The designation confers several regulatory and commercial incentives, including up to 7 years of US market exclusivity upon product approval, tax credits for qualified clinical trial expenses, and exemption from FDA application fees. ODD is awarded to therapies targeting conditions affecting fewer than 200,000 individuals in the United States.

Background and Unmet Need

GBM, the most common and lethal primary malignant brain tumor, carries a national incidence rate of approximately 3.19 per 100,000 individuals in the US. Despite multidisciplinary treatment including surgery, chemotherapy, and radiotherapy, median survival time for patients with GBM is approximately 14.6 months. Five-year survival for GBM has increased only modestly, from approximately 4% to 7%, over several decades, largely reflecting the limited progress in early detection and treatment.

A central obstacle in GBM pharmacotherapy is the blood-brain barrier (BBB), which restricts systemic drug delivery to tumor tissue. ChemoSeed is designed to address this constraint by delivering irinotecan directly into the tumor or the surgical resection margin at the time of craniotomy, thereby circumventing the BBB and sustaining local cytotoxic drug concentrations at the site of residual disease.

The implant consists of a biodegradable polymer approximately the size of a grain of rice. The open-label phase 2 study, conducted at leading UK neuro-oncology centers, is designed to evaluate the safety, tolerability, and efficacy of the implant, which delivers sustained-release irinotecan directly into the tumor resection margin after surgery.

Regulatory History and Current Trial Status

This FDA designation follows a series of regulatory milestones. The UK Medicines and Healthcare Products Regulatory Agency (MHRA) previously granted an Innovation Passport to the ChemoSeed platform under the Innovative Licensing and Access Pathway (ILAP), a designation intended to facilitate accelerated access to innovative medicines.

CRISM Therapeutics, the manufacturer, received both regulatory approval from the MHRA and a favorable ethical opinion from a UK Research Ethics Committee to initiate the open-label, registration-grade phase 2 trial of irinotecan-ChemoSeed in patients with surgically resectable GBM. The trial was confirmed to initiate in the first quarter of 2026 at selected UK neuro-oncology centers.

The phase 2 study is structured in 2 parts: an initial dose-escalation component enrolling 12 patients with recurrent GBM, followed by a randomized component enrolling 135 patients.² The primary end point is progression-free survival, with median overall survival as a secondary end point; interim results are anticipated in the first quarter of 2027.¹

"Receiving [ODD] from the FDA is a strong validation of the potential of irinotecan-ChemoSeed. From a strategic perspective, this designation enhances the regulatory profile and potential commercial attractiveness of the program and supports our strategy of advancing differentiated oncology assets that address significant unmet medical needs. When combined with our Innovation Passport and participation in the UK's ILAP program, we believe irinotecan-ChemoSeed is well positioned for constructive regulatory engagement as we progress with our registration-grade phase 2 clinical trial of irinotecan-ChemoSeed in surgically resectable [GBM],” said Chris McConville, chief scientific officer of CRISM Therapeutics, in a news release.

REFERENCES

1. Awarding of Orphan Drug Designation by the FDA. News release. CRISM Therapeutics. March 17, 2026. Accessed March 19, 2026. https://tinyurl.com/3wcbmp86

2. Irinotecan-ChemoSeed in Surgically Resectable Glioblastoma (OPTICAL). ClinicalTrials.gov. Updated January 26, 2026. Accessed March 19, 2026. https://clinicaltrials.gov/study/NCT07356973