Amsterdam Molecular Therapeutics Holding NV (AMT; in liquidation) (www.amtbiopharma.com) lost its appeal to the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP), which maintained a previous recommendation that the company's gene therapy Glybera (alipogene tiparvovec) should not be granted marketing authorization in Europe for lipoprotein lipase deficiency. CHMP reevaluated Glybera in patients with severe or multiple pancreatitis attacks, concluding that the drug's benefits did not outweigh its risks. The CHMP said evidence of Glybera's efficacy was not convincing because data from only 12 patients were available, and the reduced risk of pancreatitis seen in some patients could have been due to other factors. Despite favorable recommendations from the Committee for Advanced Therapies and Scientific Advisory Group, the CHMP voted 16 to 15 for Glybera “under exceptional circumstances,” but 17 votes were required. Publicly traded AMT said it will liquidate and delist itself by summer, following completion of its sale to privately held uniQure BV.
The EMA (www.ema.europa.eu) released for public consultation its “Reflection Paper on Classification of Advanced Therapy Medicinal Products.” The paper clarifies the legal basis for the classification of medicines as advanced therapies and provides information on how these medicines are classified—as gene therapy, somatic cell therapy, tissue-engineered, or combined medicines. It also gives details on the types of information applicants need to submit to the EMA when applying for classification of their medicine as an advanced therapy, and discusses some borderline cases, as well as areas where scientific knowledge is limited or evolving rapidly. The reflection paper is open for comments until July 31. Comments should be sent to advancedtherapies@ema.europa.eu.
ReGenX Biosciences, LLC (www.regenxbio.com) received an orphan drug product designation from the U.S. Food and Drug Administration (FDA) for its program to treat homozygous familial hypercholesterolemia (HoFH). ReGenX uses an NAV rAAV8 vector expressing a normal copy of the human low-density lipoprotein receptor (hLDLR) gene. Research from ReGenX academic collaborators James M. Wilson, M.D., Ph.D., and Daniel J. Rader, M.D., both from the University of Pennsylvania, had shown in a mouse model of HoFH that delivery of functional hLDLR to the liver via NAV rAAV8-mediated gene delivery results in dramatic decreases in circulating LDL-derived cholesterol. ReGenX is working with academic partners to develop a clinical program intended to support licensure of an HoFH treatment.
A single administration of an adeno-associated virus (AAV)-based anticocaine vaccine dramatically reduced the need for proactive engagement by individuals abusing the drug. In a study published in GEN sister journal Human Gene Therapy (http://online.liebertpub.com/hum), researchers from Weill Cornell Medical College, the Scripps Research Institute, and Cornell University found that nonhuman primate serotype AAVrh.10 can serve as a vehicle for the expression of an anticocaine antibody, enabling the vaccine to stimulate the body's own immune system to block cocaine molecules from reaching the brain, thus preventing the drug's effects before it could produce pleasurable sensations. The approach represents an important addition to the future toolbox of therapeutic interventions for cocaine addiction, where current alternatives remain only behavioral therapies, the research team concluded. In March, Weil Cornell signed an agreement with Immunovaccine (http://imvaccine.com) to advance the vaccine.
A phase I trial using a single intranodal injection of Ad-ISF35 in 15 patients with chronic lymphocytic leukemia (CLL) showed that the gene immunotherapy is feasible and safe. The replication-defective adenoviral vector expresses chimeric humanized CD154, the ligand for CD40, which is expressed on CLL cells. Binding of the ligand enhanced the ability of Ad-ISF35-treated CLL cells to function as antigen-presenting cells, generating an anti-leukemia immune response. Six patients did not require additional therapy for more than 6 months, and three achieved partial remission. The results from the first-in-human trial, published in Cancer Research, provide the rationale for future phase II studies in CLL, lymphomas, and CD40-expressing solid tumors, according to the team of researchers from the University of California, San Diego, and the CLL Research Consortium.
