FDA Pipeline: Designations in Glioblastoma, Neurofibromatosis, Multiple Myeloma, and AML


This week, the U.S. Food and Drug Administration (FDA) granted designations for treatments for recurrent glioblastoma, neurofibromatosis type 1 and plexiform neurofibromas, multiple myeloma, and relapsed or refractory FLT3-ITD acute myeloid leukemia (AML).

Fast Track Designation for Ad-RTS-hIL-12 Plus Veledimex in Recurrent Glioblastoma

The FDA granted Fast Track designation for Ad-RTS-hIL-12 plus veledimex for the treatment of recurrent or progressive glioblastoma multiforme in adults. Ad-RTS-hIL-12 is an inducible adenoviral vector encoding human pro-inflammatory cytokine interleukin-12 (IL-12), which is under the transcriptional control of the RheoSwitch Therapeutic System. Veledixmex is an oral activator ligand.

Data previously presented suggest that Ad-RTS-hIL-12 with 20mg veledimex improves the median overall survival from 6 to 9 months seen with available therapies to 12.7 months, with further improvement in median overall survival to 17.8 months in a subset of subjects with reduced cumulative steroid exposure during the active dosing period of veledimex. 

At the 2018 Annual Meeting of the Society for Neuro-Oncology, data from a phase I dose-escalation trial was presented. It showed that controlled IL-12 had a positive survival benefit, with 15 patients who received 20 mg of veledimex reaching a median overall survival of 12.7 months at a mean follow-up of 13.1 months. A subset of these patients (n = 6) who received low-dose steroids (20 mg or less of dexamethasone cumulatively over 15 days while receiving veledimex) had a median overall survival of 17.8 months compared to a median overall survival of 6.4 months for patients (n = 9) who received more than 20 mg of dexamethasone during the same period. 

Selumetinib Granted Breakthrough Therapy Designation in Neurofibromatosis Type 1

The FDA granted Breakthrough Therapy designation for the investigational MEK1/2 inhibitor and potential new medicine selumetinib. This designation is for the treatment of pediatric patients aged 3 years and older with neurofibromatosis type 1 symptomatic and/or progressive, inoperable plexiform neurofibromas.

The designation is based on phase II data from the SPRINT trial. The results of the trial were presented by Gross et al at the 2018 ASCO Annual Meeting (Abstract 10503). Selumetinib was granted Orphan Drug designation for the treatment of neurofibromatosis type 1 by the FDA in February 2018 and the European Medicines Agency in August 2018.

Investigational New Drug Application Approval for UCARTCS1 in Multiple Myeloma

The FDA approved an investigational new drug (IND) application to initiate a phase I clinical trial for UCARTCS1 in patients with multiple myeloma. The IND for UCARTCS1 was filed on December 28, 2018, and approved by the FDA on January 25, 2019.

UCARTCS1 is an allogeneic, off-the-shelf, gene-edited T-cell product candidate designed for the treatment of multiple myeloma. UCARTCS1 is based on a tailored manufacturing process that removes both the CS1 antigen and the T-cell receptor from the T-cell surface using gene editing technology, before adding the CS1 chimeric antigen receptor (CAR) construct. This approach has both clinical and operational benefits: the UCART is designed to have a lymphodepleting effect, and the CAR T-cell cross-reaction is suppressed, allowing for successful manufacturing.

UCARTCS1 is the first allogeneic CAR-T therapy for multiple myeloma to enter clinical development.

Update on Ongoing FDA Review of Quizartinib for Relapsed or Refractory FLT3-ITD AML

The FDA has extended the review period for the new drug application for quizartinib, an investigational FLT3 inhibitor, currently under Priority review for the treatment of adult patients with relapsed/refractory FLT3-ITD AML. The new Prescription Drug User Fee Act (PDUFA) action date is August 25, 2019. The FDA extended the action date by 3 months to allow time to review additional data submitted in association with an FDA request.

Quizartinib is an oral selective type II FLT3 inhibitor currently under regulatory review with the FDA, the European Medicines Agency, and the Japan Ministry of Health, Labour, and Welfare for the treatment of adult patients with relapsed or refractory AML that is FLT3-ITD positive.

Regulatory submissions in the United States, European Union, and Japan are based on the results of the pivotal phase III QuANTUM-R study of quizartinib, which was the first randomized phase III study to show that a FLT3 inhibitor prolonged overall survival as an oral, single agent compared to chemotherapy in patients with relapsed/refractory FLT3-ITD AML.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.