FDA Grants Orphan Drug Status to Irinotecan-ChemoSeed for Malignant Glioma

The FDA has granted orphan drug designation to irinotecan for the treatment of malignant gliomas, expanding beyond the original designation request for glioblastoma to include all high-grade—grade III and IV—gliomas, according to a press release from the developer, CRISM Therapeutics Corporation.¹

The designation follows the UK’s Medicines and Healthcare products Regulatory Agency awarding an Innovation Passport to the ChemoSeed platform under the Innovative Licensing and Access Pathway (ILAP) in August 2024.²

ChemoSeed is a drug delivery system capable of delivering chemotherapy directly into cancer tissues; each ChemoSeed consists of a biocompatible and biodegradable polymer that contains a chemotherapeutic drug. The developers claim they can be multilayers; thus, up to 4 drugs can be delivered at once, with different release rates and dosing enabling personalized treatment.

According to the investigators, having both ILAP participation in the UK and orphan drug designation in the US puts irinotecan-ChemoSeed in a “strong” position for regulatory interaction across major jurisdictions.

Currently, the registrational, open-label phase 2 OPTICAL trial (NCT07356973) is underway, which is evaluating irinotecan-ChemoSeed in patients with surgically resectable glioblastoma.³

Professor Chris McConville, of Ulster University, as well as the chief scientific officer of CRISM Therapeutics, stated, “Receiving Orphan Drug Designation 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 glioblastoma.”

The OPTICAL trial is structured in 2 distinct parts to address both recurrent and newly diagnosed patient populations. Part 1 of the study focuses on patients with radiologically relapsed, neuropathologically verified glioblastoma. This phase is primarily concerned with safety and determining the maximum tolerated dose and the recommended phase 2 dose of the local treatment. Investigators will initiate dose escalation at a starting dose of 72 mg of irinotecan, concurrent to standard-of-care treatment, while evaluating the feasibility of the delivery method when implanted directly following the removal of the tumor.

In part 2 of the investigation, 135 patients with newly diagnosed, radiologically suspected glioblastoma will be enrolled to assess the therapeutic efficacy of the treatment. The amount of irinotecan-ChemoSeed administered into the resected tumor margin of the tumor cavity will be at the discretion of the neurosurgical consultant, up to the maximum tolerated dose. Patients will also be randomly assigned in a 2:1 ratio to arm 1, where patients receive irinotecan-ChemoSeed plus standard of care starting 4 to 6 weeks after surgery, or arm 2, where patients receive standard of care starting 4 to 6 weeks after surgery.

The primary end point for part 2 of the study is progression-free survival, evaluated over a 39-month period. Secondary efficacy measures include the overall response rate at 6 months and the disease control rate at 12 months, both assessed via MRI using RANO 2.0 criteria through independent central review and investigator assessment. Additionally, researchers will compare the median overall survival between the treatment arms to further define the clinical benefit of localized chemotherapy delivery.

To be eligible for the trial, patients must be at least 18 years of age and present with glioblastoma amenable to maximal safe surgical resection. Inclusion criteria require a Karnofsky performance status of 70 or higher and a life expectancy of at least 6 months. Patients must also demonstrate adequate organ and marrow function, defined by an absolute neutrophil count of at least 1.5 k/µL, a platelet count of at least 100 k/µL, and a hemoglobin level of 9 g/dL or higher. Renal and hepatic function must also meet specific thresholds, including a serum creatinine level of 1.8 mg/dL or less or a creatinine clearance greater than 50 mL/min.

Patients are excluded if they present with multicentric disease, defined by tumors in multiple discrete areas without connecting signal abnormalities, or diffuse leptomeningeal disease. Other exclusion criteria include a known hypersensitivity to irinotecan and prior active malignancy except for non-melanoma skin cancer and carcinoma in situ, unless diagnosed more than 3 years prior to surgical resection.

References

1. Awarding of orphan drug designation by the FDA. News release. CRISM Therapeutics Corporation. March 17, 2026. Accessed March 18, 2026. https://tinyurl.com/3eepmp95
2. ChemoSeed. CRISM Therapeutics. Accessed March 18, 2026. https://tinyurl.com/mpvpnauv
3. Irinotecan-ChemoSeed in surgically resectable glioblastoma (OPTICAL). ClinicalTrials.gov. Updated January 26, 2026. Accessed March 18, 2026. https://tinyurl.com/2h65v4c8