FDA Clears IND of VNX-101 in CD19+ Acute Lymphoblastic Leukemia

• The FDA has cleared an investigational new drug (IND) application for VNX-101 for the treatment of CD19-positive acute lymphoblastic leukemia (ALL).
• VNX-101 is the first gene therapy product candidate from Vironexis Biotherapeutics.
• Enrollment of a phase 1/2 trial (NCT06533579) evaluating VNX-101 is expected to begin in the fourth quarter of 2024.

The FDA has cleared an IND application for the gene therapy VNX-101 in treating CD19-positive ALL, and a phase 1/2 study of the agent will commence later in 2024.¹

This study marks the first-ever clinical trial of an adeno-associated virus (AAV)-delivered cancer immunotherapy.

Previously, VNX-101 has been granted both a fast track designation and a rare pediatric disease designation from the FDA.

“We’re excited to launch Vironexis from stealth and reveal our noteworthy progress advancing AAV-delivered T-cell immunotherapy,” said Samit Varma, co-founder and chief executive officer of Vironexis, in a press release. “Our novel technology builds on the power of T-cell immunotherapy while overcoming key shortcomings and challenges of existing approaches such as CAR [chimeric antigen receptor] T and bispecific antibodies.”

“We believe we have the opportunity to dramatically improve upon the safety, efficacy and durability of these drug classes, while streamlining manufacturing and significantly lessening the burden of treatment for patients. Our focus on execution has yielded an expansive pipeline and a clinic-ready lead program in just three years. We’re working as quickly as possible to transform the future of cancer treatments for patients,” continued Varma.

VNX-101 is an investigational AAV gene therapy made to express a secreted anti-CD19/anti-CD3 scFv diabody.²

Microscopic images of blood cells as a result of leukemia: © AkuAku - stock.adobe.com

In the 2-part phase 1/2 study, dose-finding data from part 1 will be used to determine the dose for part 2. Part 1 is a pharmacokinetic (PK) study where an estimated 12 patients with marrow blasts <5% will be included. Patients must be aged 18 years or older for enrollment in this part of the trial. Before being treated with VNX-101, patients are eligible to undergo standard-of-care chemotherapy to meet dosing criteria.

In part 2, approximately 14 patients at higher disease burden (marrow blasts <50%) will be evaluated to determine the safety and PK of VNX-101 at the recommended phase 2 dose. In this part, enrollment will be expanded to include subjects 13 years of age and older. Patients will be followed, and safety and efficacy will be evaluated for up to 5 years post-VNX-101 dosing. Additionally, long-term follow-up assessments for safety are expected to be conducted for 6 to 15 years following treatment with VNX-101.

The primary end point of the trial is to evaluate treatment-emergent adverse events and treatment-emergent serious events. Secondary end points include change from baseline in B-cell counts, change from baseline in immunoglobulin levels, change from baseline in antitumor activity, and the proportion and duration of patients achieving hematological response, progression-free survival, and disease-free survival.

“AAV is a proven delivery technology with multiple approvals since 2017. Recognizing the pivotal impact of AAV delivery for the treatment of rare diseases, we believed its unique ability to enable long-term, continuous expression of a therapeutic protein could be the missing link to overcome the myriad challenges associated with first-generation T-cell immunotherapies like CAR T. We subsequently demonstrated the potential of this approach in the preclinical setting,” said Timothy Cripe, MD, PhD, chief of the Division of Pediatric Hematology/Oncology/Bone and Marrow Transplant at Nationwide Children’s Hospital, in the press release.¹ “It’s thrilling to now be on the cusp of seeing how this technology translates in the clinical setting. Our ultimate goal is to help a vastly broader population of patients realize the tremendous benefits of T-cell immunotherapy.”

REFERENCES:

1. Vironexis biotherapeutics launches with FDA clearance of IND application for first-ever clinical trial of an AAV-delivered cancer immunotherapy. News release. Vironexis Biotherapeutics. September 12, 2024. Accessed September 12, 2024. https://tinyurl.com/5cefb6dh

2. Gene therapy for B-cell acute lymphoblastic leukemia. ClinicalTrials.gov. Updated August 1, 2024. Accessed September 12, 2024. https://clinicaltrials.gov/study/NCT06533579