EMA Grants Orphan Drug Designation to CAN-2409 for Glioma

The European Medicines Agency Committee for Orphan Medical Products has granted an orphan drug designation to CAN-2409 for the treatment of patients with glioma.

The European Medicines Agency (EMA) Committee for Orphan Medical Products has granted an orphan drug designation (ODD) to CAN-2409 for the treatment of patients with glioma, according to an announcement from Candel Therapeutics.1

CAN-2409 is a genetically modified adenovirus designed to encode the herpes simplex virus thymidine kinase (HSV-tk) gene. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills infected and nearby cancer cells.

“Glioma, while mercifully rare, is a devastating disease with significant morbidity and mortality. The EMA’s ODD recognizes the high unmet need and the potential of CAN-2409 in this patient population,” Paul Peter Tak, MD, PhD, FMedSci, president and chief executive officer of Candel Therapeutics, stated in a press release. “We look forward to working with the EMA and FDA in an effort to bring our investigational medicine to patients as we initiate our phase 3 clinical trial of CAN-2409 in high-grade glioma this year.”

Intratumoral administration of CAN-2409 leads to immunogenic cell death and the release of tumor-specific neoantigens in the tumor microenvironment. Additionally, the adenoviral vector elicits a strong pro-inflammatory effect in the tumor microenvironment to induce a specific CD8-positive cytotoxic T-cell–mediated immune response against the injected tumor and uninjected distant metastases.

This dual mechanism could allow CAN-2409 to generate a powerful and lasting immune response against a variety of the patient’s tumor-associated neoantigens, minimizing the possibility for immune escape and development of tolerance.

CAN-2409 is under investigation in multiple ongoing clinical trials in high-grade glioma, non–small cell lung cancer, pancreatic cancer, and prostate cancer. A phase 1 trial (NCT03576612) evaluating CAN-2409 in combination with nivolumab (Opdivo) and standard-of-care radiation and temozolomide (Temodar) in newly diagnosed patients with high-grade gliomas completed enrollment in April 2021.2

The trial enrolled patients with an operable brain tumor presumed to be high-grade glioma based on clinical and radiologic evaluation, and pathologic confirmation of high-grade glioma was required at the time of surgery prior to CAN-2409 injection, if not previously determined.3 Patients were also required to have a Karnofsky performance status of at least 70%, an absolute neutrophil count of 1500/μL, platelets of at least 100,000/μL, and hemoglobin of at least 9 g/dL.

Previous treatment with radiation, chemotherapy, immunotherapy, therapy with a biologic agent, and hormonal therapy was not permitted. Prior glucocorticoid therapy was allowed. Key exclusion criteria included a history of hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition to valacyclovir, acyclovir, or temozolomide, a history of severe hypersensitivity reaction to any monoclonal antibody, the need for systemic immunosuppressive drugs except corticosteroids, or a history of active autoimmune disease requiring treatment within 2 years of study enrollment.

Once enrolled, patients underwent tumor resection and received a CAM-2409 injection into the wall of the resection cavity. Oral valacyclovir was then administered 3 times per day for 14 days, and on day 8, patients began radiation therapy 5 days per week for 6 weeks. Treatment with temozolomide began on day 15 after the completion of valacyclovir and was continued until a patient’s MGMT methylation status was determined.

Patients found to be unmethylated discontinued temozolomide, and these patients were classified as cohort 1. Cohort 2 consisted of patients with methylated MGMT, and they continued temozolomide. Those with undetermined MGMT methylation status were classified into cohort 2 and continued temozolomide.

All patients received intravenous nivolumab every 2 weeks for up to 52 weeks or until disease progression or unacceptable toxicity.

The primary end point of the trial is the incidence of adverse effects. Secondary outcomes included overall survival, progression-free survival, immune profiling, tumor mutation, peripheral blood mononuclear cells, and immune characterization.

In June 2021, the FDA granted a fast track designation to CAN-2409 in combination with valacyclovir following standard-of-care treatment in newly diagnosed high-grade glioma.1


  1. Candel Therapeutics receives orphan drug designation from the European Medicines Agency for CAN-2409 in glioma. News release. Candel Therapeutics. September 15, 2022. Accessed September 16, 2022. https://yhoo.it/3eZ2Cyx
  2. Candel Therapeutics completes enrollment in phase 1 clinical trial of CAN-2409 in combination with Opdivo® (nivolumab) for the treatment of high-grade gliomas. News release. Candel Therapeutics. April 22, 2021. Accessed September 16, 2022. https://bit.ly/3BMkVjm
  3. GMCI, nivolumab, and radiation therapy in treating patients with newly diagnosed high-grade gliomas (GMCI). ClinicalTrials.gov. Updated August 8, 2022. Accessed September 16, 2022. https://clinicaltrials.gov/ct2/show/NCT03576612