ALS gene therapy targeting TDP-43 protein put on FDA fast track
VectorY treatment aims to clear toxic clumps
- VTx-002, a gene therapy for ALS, received FDA fast-track designation.
- It targets and clears toxic TDP-43 protein clumps, a hallmark of ALS.
- A Phase 1/2 clinical trial (PIONEER-ALS) is evaluating its safety and efficacy.
The U.S. Food and Drug Administration (FDA) has granted fast-track designation to VectorY Therapeutics’ lead investigational therapy, VTx-002, to treat amyotrophic lateral sclerosis (ALS).
The antibody gene therapy is designed to clear toxic TDP-43 protein clumps, a hallmark of ALS.
Fast-track status is designed to expedite the development and review of therapies for serious conditions with a significant unmet medical need. It provides developers with more frequent interactions with the FDA, and it may also make a treatment eligible for priority review or accelerated approval in the future, if certain criteria are met.
“ALS is a devastating and relentlessly progressive disease with profound unmet medical need, and patients urgently need new therapeutic options,” Jim Scibetta, CEO of VectorY, said in a company press release. “The FDA’s decision to grant Fast Track designation to VTx-002 underscores the seriousness of ALS and the importance of advancing new investigational approaches.”
Abnormal TDP-43 protein aggregates are observed in about 97% of ALS patients and are believed to contribute to nerve cell damage. Clearing these toxic clumps is therefore regarded as a promising strategy to slow or prevent disease progression in most patients.
Long-lasting results
VTx-002 is designed to enable nerve cells to produce antibodies that target toxic TDP-43 aggregates, flagging them for clearance by the body’s immune system.
The therapy was developed with VectorY’s vectorized antibody technology, which uses a harmless adeno-associated virus (AAV) to deliver the genetic blueprint for an antibody directly to cells in the brain and spinal cord. This enables those cells to produce the therapeutic antibody on their own.
In VTx-002, the AAV delivers a gene encoding an antibody that binds to the abnormal form of TDP-43 while sparing the protein’s normal form. Because the viral vector remains inside cells until they die, a single administration is expected to result in long-lasting antibody production and potentially durable therapeutic effects.
This contrasts with traditional antibody drugs, which typically require repeated dosing as antibodies degrade over time and lose their effectiveness. Regular antibodies are also often too large and struggle to reach the brain and spinal cord, which can limit their ability to fight neurological conditions.
The FDA recently cleared VectorY’s investigational new drug (IND) application for VTx-002, which opened the door for the therapy to enter clinical testing in ALS.
The company is conducting an open-label Phase 1/2 clinical trial, PIONEER-ALS (NCT07287397), which aims to evaluate the safety, tolerability, and biological activity of VTx-002 in about 12 adults with ALS.
Participants will receive one of two doses of the investigational therapy, administered via an injection into the cisterna magna, a large fluid-filled space at the base of the brain. They will then be followed for about five years.
Enrollment is ongoing at one site in Boston, with sites in the U.S. and Europe expected to open soon.
“This designation enables closer and more frequent interaction with the FDA as we … advance VTx-002 into the … PIONEER-ALS Phase 1/2 clinical study, with the goal of moving as efficiently and responsibly as possible on behalf of patients,” Scibetta said.
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