uniQure Expands Neurological Gene Therapy Pipeline With Epilepsy Program Acquisition


Corlieve Therapeutics’ lead program, AMT-260, previously demonstrated proof-of-concept in preclinical studies of temporal lobe epilepsy.

uniQure has expanded its efforts to investigate gene therapy strategies for the treatment of temporal lobe epilepsy (TLE) through acquiring Corlieve Therapeutics and its lead program, AMT-260.1

The acquisition expands uniQure’s gene therapy pipeline in neurological disorders, specifically therapies that employ miRNA silencing technology. The AMT-260 program has previously demonstrated proof-of-concept in preclinical studies that show clear suppression of chronic spontaneous epileptic seizures.

“The acquisition of Corlieve provides an extraordinary opportunity to transform the lives of hundreds of thousands of patients around the world suffering from epilepsy and aligns with our vision of pursuing unmet medical needs for disorders that impact large populations and can be addressed with gene therapies directed to the CNS and liver,” Matt Kapusta, chief executive officer, uniQure, said in a statement.

“The groundbreaking work of the Corlieve team, in collaboration with Drs Mulle and Crepel, has led to compelling preclinical results in TLE that we believe can strategically leverage uniQure’s leading position in developing and delivering gene therapies that employ miRNA silencing technology. We look forward to welcoming the Corlieve team into the uniQure family as we join forces to advance this important and potentially transformative therapy into clinical studies,” he continued.

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AMT-260 uses miRNA silencing to target suppression of aberrantly expressed kainate receptors in the hippocampus in patients with TLE. It was originally developed by Corlieve in collaboration with Christophe Mulle, PhD, CNRS Research Director, Interdisciplinary Institute of Neurosciences, CNRS, University of Bordeaux, and Valerie Crepel, PhD, Inserm Research Director, Institut de Neurobiologie de la Méditerranée, INSERM, Aix-Marseille University, as well as REGENXBIO.

“With the dedication and focus of our team and our collaboration partners, we have taken a promising therapeutic approach discovered by our scientific founders and created a potential transformative therapeutic opportunity for patients with refractory TLE,” said Richard Porter, PhD, founder and chief executive officer, Corlieve. “As leaders in the field for miRNA gene therapy for neurological conditions, uniQure is the ideal long-term partner for us, and we look forward to working together to advance our program rapidly to the clinic for the benefit of the patients we serve.”

uniQure also recently announced positive data from their phase 3 HOPE-B study (NCT03569891) of etranacogene dezaparvovec for the treatment of hemophilia B. The multinational, open-label, single-arm study enrolled 54 participants with severe or moderately severe hemophilia B (no more than 2% Factor IX [FIX] activity) that required prophylactic FIX replacement therapy.2

Participants treated with etranacogene dezaparvovec exhibited sustained increases in FIX activity as measured by a one-stage APTT-based clotting assay, with an increase from 39.0% of normal mean FIX activity at 26-weeks of follow-up to 41.5% of normal mean FIX activity at 52 weeks. No significant correlation was seen between pre-existing neutralizing antibodies to adeno-associated virus serotype 5 (AAV5; NAbs) and FIX activity in patients with NAb titers up to 678.2.

Investigators found a 96% reduction in use of FIX replacement therapy in all patients during the interventional period. Fifty-two (96%) discontinued the therapy entirely. Of the 2 non-responders, 1 received a partial dose due to an infusion reaction and the second had an unusually high pre-existing NAb titer of 3,212. No treatment-related serious adverse events were observed. No inhibitors to FIX have been reported and no significant association between safety and pre-existing NAb titers has been observed.

“The 52-week data show mean FIX activity in the normal range and increase our confidence in the potential durability and long-term benefits of etranacogene dezaparvovec, bringing us one step closer to our goal of delivering this groundbreaking therapy to fulfill an unmet medical need for patients living with hemophilia B,” Ricardo Dolmetch, PhD, president, research and development, uniQure, said in another statement.

The data come shortly after the FDA lifted the clinical hold on the trial, which was placed in December 2020, following a report of hepatocellular carcinoma in a single patient receiving treatment in the trial. 

The company said that they intend to seek approval for the gene therapy in the first quarter of 2022.

1. uniQure to acquire Corlieve Therapeutics and advance its gene therapy program to treat temporal lobe epilepsy (TLE). News release. UniQure. June 22, 2021. https://www.globenewswire.com/news-release/2021/06/22/2251226/0/en/uniQure-to-Acquire-Corlieve-Therapeutics-and-Advance-its-Gene-Therapy-Program-to-Treat-Temporal-Lobe-Epilepsy-TLE.html
2. uniQure announces positive 52-week clinical data from HOPE-B pivotal trial of etranacogene dezaparvovec gene therapy in patients with hemophilia B and provides regulatory update. News release. UniQure. June 22, 2021. https://www.globenewswire.com/news-release/2021/06/22/2251227/0/en/uniQure-Announces-Positive-52-Week-Clinical-Data-from-HOPE-B-Pivotal-Trial-of-Etranacogene-Dezaparvovec-Gene-Therapy-in-Patients-with-Hemophilia-B-and-Provides-Regulatory-Update.html
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