FDA Grants Orphan Drug Designation to Silmitasertib To Treat Medulloblastoma

The FDA’s orphan designation for silmitasertib for medulloblastoma marks the drug’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 from Senhwa Biosciences.1

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

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

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

The study has 3 experimental arms. Arm 1 is made from immature children with refractory or relapsing medulloblastoma. Arm 2 consists of adult patients with refractory or recurrent medulloblastoma. Arm 3 consists of patients who qualify for arm 1 or 2 and are candidates for surgery. Each arm is given 200 mg of the drug orally.

“We are happy to receive [orphan drug designation] for silmitasertib for medulloblastoma, a rare, serious pediatric disease for which there are no approved targeted therapies. [Orphan drug designation] represents an important regulatory milestone that has the potential to accelerate 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

To participate in the study, patients must also have received prior therapy, including radiation therapy, must have received the last dose of another study or biologic agent 7 days or less prior to therapy, must have received the last dose of myelosuppressive therapy 21 days before enrollment are 6 months or more since allogeneic stem cell transplant, and 3 months or more since the last autologous stem cell transplant. Patients must also be cleared of all colony-forming growth factors at least 1 week prior to enrollment.

Nursing mothers, patients with a history of other malignancy, difficulty swallowing, active malabsorption, uncontrolled diarrhea, gastritis, ulcerative colitis, Crohn’s disease or hemorrhagic, clinically significant unrelated systemic disease, or patients taking 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.

REFERENCES:1. Senhwa’s silmitasertib receives FDA orphan drug designation from us for the treatment of medulloblastoma. news item. senhwa. December 16, 2021. Accessed December 20, 2021. https://bit.ly/3J5oCSB2. Testing the safety and tolerability of CX-4945 in patients with recurrent or nonoperative medulloblastoma. ClinicalTrials.gov. Accessed on December 20, 2021. https://bit.ly/3mjWIZv

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