FDA Grants Fast Track Designation to Enzastaurin in Newly Diagnosed Glioblastoma

Enzastaurin (DB102), a first-in-class small molecule, has been granted a Fast Track designation by the FDA for the potential treatment of patients with newly diagnosed glioblastoma multiforme, Denova Biopharma announced in a press release.¹

"This Fast Track designation in glioblastoma is an important milestone in the development of DB102," said Xiao-Xiong Lu, PhD, chief technical officer, Denova, in a statement. "We are pleased that FDA has recognized our innovative biomarker approach to conquer glioblastoma. It potentially accelerates our development of DB102 in glioblastoma, a difficult-to-treat indication with a significant unmet need and adds value to our DB102 franchise."

Enzastaurin was taken into development after the novel DGM1 biomarker was discovered by Denova Biopharma and after multiple attempts to address the lack of survival among patients with glioblastoma, a disease for which physicians continue to rely on temozolomide (Temodar) as the backbone of their treatment. Additionally, the efficacy outcomes associated with anticancer drugs that have become available for the treatment of this disease are not as good as temozolomide. The limited efficacy in the current treatment landscape for glioblastoma warrants further research on novel agents.

To address the need for novel drug, Denova Biopharma plans to launch a pivotal phase 3 clinical trial of enzastaurin plus temozolomide, both during and after radiation therapy in patients with newly diagnosed glioblastoma.

A phase 2B study is already investigating the efficacy enzastaurin plus temozolomide in 200 patients with newly diagnosed glioblastoma with or without the DGM1 biomarker. Permission from the FDA to proceed with this biomarker-guided trial was granted in October of 2019 after the developer submitted an Investigational New Drug Application for enzastaurin. The primary end point of the study is overall survival, an important outcome considering that the 5-year survival rate for patients with glioblastoma is less than 5 years.²

The randomized, double-blind, placebo-controlled, multicenter study randomizes patients to receive either enzastaurin plus temozolomide during or after radiotherapy or placebo plus temozolomide before or after radiotherapy.

To be eligible for the study, patients must be 18 years of age or older with histologically confirmed newly diagnosed glioblastoma, a Karnofsky performance score ≥ 60, a life expectancy of at least 12 weeks, and adequate organ function within 14 days of randomization. Patients who had a prior craniotomy must be healed and free of drainage and cellulitis before starting the trial, and those who have undergone resection must be randomized within 5 weeks of their procedure. Any patients taking corticosteroids must be stable or receiving a decreasing dosage within 5 days of receiving study treatment.

The study excludes individuals who have had previous chemotherapy, immunotherapy, or an investigational drug for glioblastoma. In addition, anyone who has had brain radiotherapy is ineligible to join the study. Patients with active bacterial, fungal, or viral infection, another malignancy, and/or severe acute or chronic medical or psychiatrics conditions are also deemed ineligible to receive enzastaurin plus temozolomide in the study.

In prior research around enzastaurin in glioblastoma, the agent was studied in over 3,000 patients with solid and hematologic malignancies. The agent is known to inhibit the PKC beta, PI3K, and AKT pathways. The most advanced research for enzastaurin is in the diffuse large B-cell lymphoma space, in which the drug received an Orphan Drug designation by the FDA and the European Medicine Agency.

_References:

_{FDA grants Fast Track designation for db102 in patients with newly-diagnosed glioblastoma (GBM). News release. Denova Biopharma. July 17, 2020. Accessed July 17, 2020. https://prn.to/3fEw3RF}

_{Denovo Biopharma receives FDA's Permission to proceed with a biomarker-guided phase 2b clinical trial with db102 (enzastaurin) in first-line treatment of glioblastoma (GBM). News release. Denova Biopharma. October 15, 2019. Accessed July 17, 2020. https://bit.ly/3jb8qlX}