JNJ-2056, Targeting Tau Protein, Receives FDA Fast Track Designation for Alzheimer Disease

The FDA has granted a fast track designation to JNJ-2056, previously known as ACI-35.030, which can target the pathological form of the Tau protein—phosphorylated Tau (pTau)—and potentially reduce the effects of Alzheimer disease (AD), according to a news release from AC Immune SA.¹

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Currently, the phase 2b ReTrain clinical trial is recruiting individuals with preclinical AD where individuals have not yet shown any clinical symptoms. The trial is intended to analyze whether JNJ-2056 has a disease-modifying effect that can prevent the onset of the disease.^1,2

“The Phase 2b ReTain study is the first time any active immunotherapy is being tested in a preclinical AD population,” Andrea Pfeifer, CEO of AC Immune SA, said in the news release. “We believe this modality has the potential to offer therapeutic advantages, as well as benefits in terms of convenience and access.”¹

The multicenter, double-blind, placebo-controlled study includes 500 patients, randomly assigned 1:1 to a single dose of JNJ-2056 immunization or placebo for a maximum of 4 years.²

The primary end point of the study measures cognitive decline, assessed by the Preclinical AD Cognitive Composite 5 (PACC-5) score. A secondary efficacy end point will analyze the effect that JNJ-2056 has on the accumulation of Tau pathology compared to placebo, which is measured by Tau PET imaging.¹

JNJ-2056 has been designed to enhance the creation of broad-spectrum protective antibodies against pTau. It has the potential to reduce pTau spreading in the early stages of AD, and therefore could reduce the progression of the disease before becoming too severe.¹

Prior to this, a phase 1b/2a trial indicated that the immunization could activate patients’ immune systems with a “robust polyclonal antibody response” against pTau and its aggregated form. In the trial, both vaccinations of JNJ-2056 and another anti-tau vaccine from AC Immune, JACI-35.054, were determined to be safe and led to a strong, sustained anti-pTau response.²

The potential vaccine and the phase 1b/2a trial details were initially presented at the 2022 Clinical Trials on Alzheimer Disease conference. Patients included in the study population were 50- to 75-year-old men and women with mild AD or mild cognitive impairment, based on guidelines from the National Institute of Aging.²

“We believe this modality has the potential to offer therapeutic advantages, as well as benefits in terms of convenience and access,” Pfeifer continued. “Fast Track designation offers opportunities for more efficient development and regulatory review.”¹

JNJ-2056 is being jointly developed, pursuant to a global license, development and commercialization agreement, with Janssen Pharmaceuticals. The ReTrain trial is being fully conducted and funded by Janssen.¹

“More importantly, this underscores and validates the potential therapeutic impact of an active immunotherapy specifically targeting pTau, the key pathologic species of Tau protein,” Pfeifer concluded.¹

REFERENCES

1. AC Immune. AC Immune’s ACI-35.030 (now “JNJ-2056”) granted FDA Fast Track Designation for Alzheimer’s disease. News release. Released July 25, 2024. Accessed July 25, 2024. https://ir.acimmune.com/news-releases/news-release-details/ac-immunes-aci-35030-now-jnj-2056-granted-fda-fast-track#:~:text=ACI%2D35.030%20is%20designed%20to,reduce%20or%20prevent%20disease%20progression.

2. Meglio M. AC Immune advances anti-Tau vaccine ACI-35.030 to phase 2 trial. NeurologyLive. Published December 21, 2023. Accessed July 25, 2024. https://www.neurologylive.com/view/ac-immune-advances-anti-tau-vaccine-aci-35-030-phase-2-trial