FDA Grants Fast Track Designation to Silmitasertib for SHH-Driven Medulloblastoma

The FDA has granted fast track designation to the highly selective casein kinase 2 (CK2) inhibitor, silmitasertib (CX-4945), for the treatment of patients with recurrent sonic hedgehog (SHH) driven medulloblastoma, announced Senhwa Biosciences, Inc, in a press release.¹

Inhibition of CK2 has been shown to regulate cell growth and survival in many cancers. In medulloblastoma specifically, silmitasertib has the ability to decrease tumorigenesis and growth and increase apoptosis. Further, silmitasertib has synergy with the standard-of-care treatment for medulloblastoma, temozolomide (Temodar).²

“We are delighted to receive fast track designation and look forward to working closely with the FDA to accelerate the development of silmitasertib, aiming to promptly bring a meaningful treatment to patients with recurrent SHH-driven medulloblastoma," said Tai-Sen Soong, chief executive officer of Senhwa Biosciences, in a press release.

A phase 1/2 study of silmitasertib in patients with recurrent medulloblastoma who may or may not have surgery (NCT03904862) is currently recruiting an estimated 60 patients. In 3 arms, silmitasertib treatment will be assessed in patients who are skeletally-immature, skeletally-mature, and those who are candidates for surgery. In all 3 study arms, patients will receive 200 mg capsules of silmitasertib administered orally.³

The phase 1 coprimary end points are maximum-tolerated dose, pharmacokinetics (PK), and intratumoral PK concentrations. The phase 2 primary end point is sustained objective response rate. The secondary end points of the study include progression-free survival, ORR in the skeletally-immature cohort, plasma PK of silmitasertib in skeletally-mature patients, the relative frequency of genomic alteration in archival tissue, and reduction in CK2-mediated signaling in the tumor among the surgery candidates.

Screening in the study is for patients with a diagnosis of recurrent or refractory medulloblastoma with adequate tumor tissue for testing. For inclusion in the skeletally-immature cohort, patients are required to be between the ages of 3 and 18 years old, with a bone age of 14 in females and 16 in males.

For inclusion in the skeletally-mature cohort, patients must have bi-dimensionally measurable disease in addition to meeting the age and bone age requirements. Finally, for the cohort of surgical candidates, the inclusion requirements are clinically indicated surgical resection, minimum age of 3 years, and amenability to receiving silmitasertib for 5 to 7 days prior to surgery.

Nine centers in the United States are recruiting patients for this study.

With a fast track designation, an expediated review of any application for approval is warranted for silmitasertib.¹

_References:

_{1. Senhwa's silmitasertib receives US FDA fast track designation for the treatment of recurrent sonic hedgehog driven medulloblastoma. New Release. Senhwa Biosciences, Inc. August 17, 2021. Accessed August 19, 2021. https://www.senhwabio.com/en/news/20210817}

_{2. Nitta RT, Bolin S, Luo E, et al. Casein kinase 2 inhibition sensitizes medulloblastoma to temozolomide. Oncogene. 2019;38(42):6867-6879. doi: 10.1038/s41388-019-0927-y.}

_{3. Testing the safety and tolerability of CX-4945 in patients with recurrent medulloblastoma who may or may not have surgery. Clinicaltrials.gov. Accessed August 19. 2021.}