FDA Clears Samus Drug for Glioma Phase Ib Study

FDA_Sarah Silbiger/Getty Images

Sarah Silbiger/Getty Images

The U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application for PU-AD (icapamespib), an epichaperome inhibitor for recurrent malignant glioma developed by privately held biopharmaceutical company Samus Therapeutics

Clearance of the IND allows Samus to proceed with a Phase Ib trial to assess the safety, tolerability and pharmacokinetics of PU-AD in a small group of patients with recurrent malignant glioma. The two-stage study will be conducted at several U.S. sites and will be spearheaded by Dr. John de Groot of the University of Texas M.D. Anderson Cancer Center, and Dr. Howard Colman of the Huntsman Cancer Institute at the University of Utah. 

Dose escalation in the study will rely on daily PU-AD administration in patients with either a first, second or third isocitrate dehydrogenase (IDH) wild type glioblastoma recurrence, or grade 3 or 4 IDH mutant astrocytoma.

In a statement, President and Chief Executive Officer of Samus Therapeutics, Dick Bagley, said the expansion stage of the study will seek to “confirm safety of the Phase II dose” and “investigate the biology of recurrent disease through biomarker analysis and evidence of target engagement."

The American Cancer Society says glioblastoma represents the most common and aggressive primary brain tumor in adults, contributing to half of primary brain cancers. While extensive research has been funneled into this field, available therapies have not improved survival, which currently sits at 14 to 16 months. 

The current standard of care for recurrent malignant glioma includes surgery, chemotherapy and radiation.

Glioblastomas demonstrate high levels of epichaperomes, according to work led by Gabriela Chiosis, Ph.D., Samus Therapeutics’ Scientific Founder. 

“Epichaperome-driven glioblastoma cells respond well to icapamespib treatment in xenograft mouse models and ex vivo studies even when resistant to Temodar® (temozolomide) and Avastin® (bevacizumab), giving us a signal that icapamespib could have a clinical impact on this devastating disease," explained Barbara Wallner, Ph.D., the company’s Chief Scientific Officer. 

PU-AD, an orally bioavailable small molecule inhibitor of epichaperomes, shows little to no effect on normal cell proteostasis. Some researchers believe epichaperomes maintain and drive forth a pathologic cellular phenotype, thereby prevent and sometimes aid in aberrant protein degradation. 

Previously, the investigational PU-AD has demonstrated benefits in animal studies, showing it could reduce pathological tau levels and improve spatial memory/learning. 

If early and late-stage trial findings from Samus are promising, PU-AD could hold important practice-changing implications for clinical care. 

Phase 1 study results presented at last year’s Alzheimer's Association International Conference (AAIC 2020) showed PU-AD, when delivered at single doses of 10, 20, and 30 mg in healthy volunteers, was well-tolerated and showed strong blood brain barrier penetration and a favorable pharmacokinetic profile. 


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