An orphan drug designation has been granted to DSP-0390 by the FDA as treatment in patients with brain cancer.
The FDA has granted orphan drug designation (ODD) for DSP-0390, an investigational emopamil-binding protein inhibitor, for the treatment of patients with brain cancer, according to Sumitomo Pharma Oncology, Inc.1
Currently, a phase 1 clinical trial (NCT05023551) is evaluating the safety and efficacy of DSP-0390 in patients with recurrent, high-grade glioma. This study, which is being conducted in the United States and Japan, is the basis of the ODD.
An ODD was also announced for another product of Sumitomo Pharma Oncology, Inc., TP-3654, for the treatment of patients with myelofibrosis.
"This designation for DSP-0390 underscores the profound need for novel brain cancer treatment options," said Patricia S. Andrews, chief executive officer and global head of oncology of Sumitomo Pharma Oncology, Inc. "We are excited to contribute to advancing critical research in brain cancer."
Within the dose-escalation, phase 1 study examining DSP-0390 in patients with recurrent high-grade gliomas, the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of the orally administered product will be evaluated. Following the first portion, a part 2 expansion of the trial will take place.2
The study will be split into 28-day cycles to examine safety and response assessments. Patients enrolled in the study will receive DSP-0390 orally once a day and will continue treatment until progression of disease, unacceptable toxicity, withdrawal of consent, loss to follow-up, or discontinuation of the patient by the investigator, whichever comes first.
Enrollment is open to patients aged 18 and older with an estimated life expectancy over 3 months and adequate organ function. For those on an antiepileptic drug, the dose administered must be stable and patients must have had no seizures 14 days prior to study. For the dose expansion part of the study, the dose must be ≤ 4 mg dexamethasone per day (or equivalent dose if other corticosteroids are used). Additionally, females of childbearing potential are required to have a negative serum or urine pregnancy test.
The study also aims to evaluate increasing dose levels of DSP-0390 in order to determine the maximum tolerated dose (MTD) and/or a suitable lower dose for expansion in patients with recurrent WHO grade 3 or 4 malignant glioma. When the MTD is established, part 2 of the study, the dose-escalation portion, will focus on evaluating the preliminary clinical activity, safety and tolerability of DSP-0390 in patients with recurrent WHO Grade 4 glioblastoma multiforme.
Primary end points of the dose-escalation portion of the study include to assess safety of DSP-0390 by incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events, and to determine the MTD and/or recommend dose for expansion of DSP-0390. In the dose-expansion portion of the trial, primary end points are to evaluate the change in baseline tumor activity of DSP-0390 using radiologic assessments, evaluate the safety of the recommended phase 2 dose by assessment of incidence and severity of TEAEs and SAEs.
Secondary outcome measures of the dose-escalation part of the trial include to characterize the PK profile, evaluate preliminary antitumor activity, objective response, and duration of response assessed by RANO criteria. Another exploratory end point is to assess the PD effect of DSP-0390 in this patient population.
"DSP-0390 is an emopamil-binding protein inhibitor that mediates de novo cholesterol synthesis for cell membrane structure and signaling, enabling aberrant growth of tumors," added Jatin J. Shah, MD, chief medical officer of Sumitomo Pharma Oncology, Inc., in the press release. "Notably, in patients with glioblastoma multiforme, a form of high-grade glioma, increased de novo cholesterol synthesis is correlated with poor survival and preclinical evidence has shown that DSP-0390 has cytotoxic activity against glioblastoma multiforme cell lines."