Date: 2014-10-27
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the European Society of Gene and Cell Therapy (ESGCT) and Netherlands Society of Gene and Cell Therapy (NVGCT)
Company: uniQure (The Netherlands) AIPGENE Consortium
Product: AAV5-AAT-PBGD (AMT-021)
Action
mechanism: AAV5-AAT-PBGD (AMT-021) is a gene therapy.The candidate consists of the PBGD (porphobilinogen deaminase) gene encapsulated in uniQure’s proprietary AAV5 viral vector and is designed to enable transfection of the PBGD gene into patient’s liver cells through a single therapeutic intervention.
Disease: acute intermittent porphyria (AIP)
Therapeutic area: Rare diseases
Country: Spain
Trial
details: The Phase I will enroll eight patients with severe acute intermittent porphyria (AIP) at two centers: the Clinical University of Navarra, Pamplona, Spain, and the 12 de Octubre University Hospital, Madrid, Spain. The study's primary objective is the assessment of safety and determination of the maximum tolerated dose. Secondary objectives include tolerability of treatment, pharmacokinetics, changes in the levels of surrogate markers of activity including porphobilinogen (PBG) and delta-aminolevulinic acid (ALA), and assessment of symptom control, neuro-psychological changes and quality of life.
Latest
news: * On October 27, 2014, the AIPGENE Consortium, a pan-European collaboration supported by the Seventh Framework Programme, and uniQure announced the top-line one year follow-up analysis of a completed Phase I dose-escalation clinical trial testing an AAV5-PBGD gene therapy candidate (AMT-021) in Acute Intermittent Porphyria (AIP) patients. The data were presented on Saturday, October 25, at the European Society of Gene and Cell Therapy (ESGCT) and Netherlands Society of Gene and Cell Therapy (NVGCT) Collaborative Congress by Dr. Gloria González-Aseguinolaza, the Scientific Coordinator of the AIPGENE Consortium. The preliminary analysis of the data confirm the safety and successful transduction of patient's liver cells with the porphobilinogen deaminase gene (PBGD) using uniQure's proprietary AAV5 viral vector, as previously indicated in the interim analysis presented in May 2014. In the multicenter, open label, single dose, dose-ranging Phase I clinical trial, a total of eight patients in four dosing cohorts received AMT-021 doses of up to 2 x 1013 gc/kg. The trial reported no safety concerns from any patient; in particular, there was no evidence of cellular immune response against the AAV5 vector or the PBGD transgene. Humoral responses against AAV5 were detected in all patients, as expected. Vector genomes were detected in patients' liver biopsies obtained one year after vector injection indicating that AMT-021 sustainably transduced human liver cells. The Phase I trial was conducted by Digna Biotech as part of the AIPGENE Consortium. In addition to Digna, CIMA and uniQure, the consortium included the Clínica Universidad de Navarra/University of Navarra, Karolinska University Hospital, the National Center for Tumour Diseases, Heidelberg, and Servicio Madrileño de Salud, Madrid. * On May 27, 2014, uniQure announced successful transfection of liver cells with the porphobilinogen deaminase gene (PBGD) from an ongoing Acute Intermittent Porphyria (AIP) dose-escalation Phase I trial conducted in collaboration with the AIPGENE Consortium, a pan-European collaboration. The results, presented Saturday, May 24, at the 17th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT) by Dr. Gloria González-Aseguinolaza from the AIPGENE Consortium also provided evidence that the AAV5 vector from uniQure’s bacculovirus production platform is safe by inducing liver cell transfection in AIP patients without liver enzyme perturbations at the tested dose levels. In the ongoing multicenter, open label, single dose, dose-ranging Phase I clinical trial, a total of eight patients in four dosing cohorts received AMT-021 doses of up to 2 x 1013 gc/kg. The trial reported no safety concerns from any patient based on review at six months post administration. In particular, no liver enzyme perturbations have been noted at any dose level and no administration of corticosteroids has been required. The result of liver biopsies performed between week 42 - 47 in six out of the eight patients show the presence of PBGD DNA in the liver parenchymal cells demonstrating that uniQure’s exclusively licensed AAV5 vectors can be effective in infecting human liver cells and delivering the PBGD gene into liver cells. The Consortium will release full data from the clinical study later in 2014. Based on those results, uniQure will define the next steps for further clinical evaluation of AMT-021. * On December 11, 2012, uniQure has announced the start of its Phase I clinical trial in acute intermittent porphyria (AIP) with the treatment of the first patient. All patients will be followed for one year, and the interim results of the Phase I are expected in Q3 2013.
The study is conducted under the aegis of the AIPGENE consortium, a pan-European collaboration funded in part by the European Commission\'s Seventh Framework Program with the aim to develop a gene therapy for the treatment of AIP, a rare and devastating disease caused by mutations in the porphobilinogen deaminase gene (Grant Agreement number 261506). This consortium was put together with the aim to develop the orphan gene therapy drug AAV5-AAT-PBGD (AMT-021) for the treatment of AIP. The consortium\'s objective is to contribute to alleviating the negative impact of this disease on the quality of life of the patients and their families. Overall coordinator of the project is the Centre for Applied Medical Research (CIMA) at the University of Navarra, Pamplona, Spain. Apart from uniQure, other members of the consortium are the Clinical University of Navarra, Pamplona, Spain; Karolinska University Hospital, Stockholm, Sweden; German Cancer Research Center (NCT-DKFZ), Heidelberg, Germany; DIGNA Biotech, Pamplona, Spain; Servicio Madrileno de Salud, Madrid, Spain.
Last year, the European Union (EU) has finalized a € 3.3 million grantto the AIPGENE consortium, of which AMT(now uniQure) is a member, for the development of this gene therapy product. From the grant, made under the EU’s FP7 program, AMT has receveided € 1.1 million. .
uniQure was granted orphan drug designation for the treatment of AIP in 2009 from the European Medicines Agency. The start of this study also marks the first of the four uniQure programs that will enter clinical trials over the next 12 months. Clinical trials are also expected to be initiated in Parkinson\'s disease, hemophilia B, and Sanfilippo B.
