FDA Grants Orphan Drug Designation to Silmitasertib To Treat Medulloblastoma


The FDA’s orphan drug designation granted to silmitasertib for medulloblastoma marks the agent’s second such designation.

Silmitasertib (CX-4945), a casein kinase 2 (CK2) inhibitor, has been granted an orphan drug designation by the FDA for the treatment of patients with medulloblastoma, according to a press release by Senhwa Biosciences.1

Silmitasertib is a small molecule drug that targets the CK2 pathway. In addition to medulloblastoma, the agent is being investigated for tolerability and efficacy in COVID-19, along with adult and pediatric patients with recurrent/advanced or metastatic cancer. Silmitasertib previously received an orphan drug designation in 2016 for the treatment of cholangiocarcinoma; a rare pediatric disease designation in 2020 for the treatment of medulloblastoma; and a fast track designation in August 2021 for the treatment of recurrent Sonic Hedgehog-driven medulloblastoma.

The agent is currently being evaluated in a phase 1/2 study (NCT03904862) in patients with recurrent Sonic Hedgehog medulloblastoma who may or may not have surgery. The non-randomized, open-label study has a target enrollment of 60 participants and an estimated study completion date of May 2022.2

The primary end points of the study are maximum tolerated dose, pharmacokinetics, intertumoral pharmacokinetics concentrations, and sustained objective response rate. Secondary end points include progression-free survival, relative frequency of genomic alteration in archival tissue, and reduction of CK2-mediated signaling in tumor.

The study has 3 experimental arms. Arm 1 is made of skeletally immature children with refractory or recurrent medulloblastoma. Arm 2 is made up of skeletally mature subjects with refractory or recurrent medulloblastoma. Arm 3 is made up of patients who are eligible for arm 1 or 2 and are candidates for surgery. Each arm will receive 200 mg of the agent orally.

"We are pleased to receive [orphan drug designation] for silmitasertib for medulloblastoma, a rare, severe pediatric disease for which there are no approved targeted therapies. [Orphan drug designation] represents an important regulatory milestone that has the potential to expedite the clinical development of silmitasertib, a potent and selective CK2 inhibitor," said John Soong, MD, FACP, chief medical officer of Senhwa Biosciences, in a press release.1

In order to participate in the study, patients must also have received prior therapy that included radiation therapy, must have received the last dose of another investigation or biologics agent 7 days or less prior to therapy, have received the last dose of myelosuppressive therapy 21 days prior to enrollment, be 6 months or more since allogenic stem cell transplant, and must be 3 months or more since last autologous stem cell transplant. Patients must also be off all colony-forming growth factors at least 1 week prior to enrollment.

Nursing mothers, patients with a history of any other malignancy, difficulty swallowing, active malabsorption, uncontrolled diarrhea, gastritis, ulcerative colitis, Crohn’s disease, or hemorrhagic, clinically significant unrelated systemic illness, or patients who are on warfarin or statins are not eligible to participate.

The study is currently recruiting in California, the District of Columbia, Georgia, Illinois, New York, Ohio, Pennsylvania, Tennessee, and Texas.

1. Senhwa’s silmitasertib receives us fda orphan drug designation for the treatment of medulloblastoma. News release. Senhwa. December 16, 2021. Accessed December 20, 2021. https://bit.ly/3J5oCSB
2. Testing the safety and tolerability of CX-4945 in patients with recurrent medulloblastoma who may or may not have surgery. ClinicalTrials.gov. Accessed December 20, 2021. https://bit.ly/3mjWIZv

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