European Guidelines on Biosimilars to be Released in November

The European Medicines Agency (EMA) announced that it has finalized its requirements for biosimilar antibodies, and that these requirements will be made public in November ¹ . Once the guidelines are released, they will be open to external consultation for three to six months before being formally adopted, and will likely go into effect in the second half of 2011.

European regulators remain a few steps ahead of their U.S. counterparts with regard to biosimilar regulations. While the FDA is still gathering information on how to implement the new biosimilar approval pathway of the Biologics Price Competition and Innovation Act of 2010 (see October Regulator Wire) ² , thirteen biosimilars have already been approved in Europe. These include generic versions of human growth hormone, erythropoietin, and G-CSF. As with the 13 existing biosimilar drugs approved by the EMA, generic companies will have to conduct clinical trials to prove their antibody is similar to the original product on which it is based. It is likely that FDA officials and drug companies will be paying close attention to the November guidelines put forth by the EMA, as they could serve as a template for future U.S. guidance on antibody biosimilars. (sk)

NIH RAC and CliniGene to Co-host a Scientific Symposium on Retroviral and Lentiviral Vectors

The NIH recombinant DNA advisory committee (RAC) has previously reviewed clinical and molecular data concerning leukemias caused by insertional mutagenesis at or near oncogenes in two trials for X-linked Severe Combined Immunodeficiency Disease (X-SCID) involving transduction of CD34+ hematopoietic stem cells by retroviral vectors ¹ . Since these discussions, investigators have reported advances in the field, including clinical benefits in trials studying other clinical indications (e.g., adenosine deaminase deficient-SCID, adrenoleukodystrophy). In addition, research has focused on alternative vectors, either lentiviral vectors or modified retroviral vectors designed to decrease the risk of enhancer-mediated insertional mutagenesis.

Given these developments, as well as recent reports of myelodysplasia in a trial for chronic granulomatous disease ² and the finding of a relative clonal population of cells in a trial for thalassemia ³ , the RAC and the European Network for the Advancement of Clinical Gene Transfer and Therapy (CliniGene) are holding a two-day symposium to review:

1) Developments in retrovirus and lentivirus integration and insertional mutagenesis research, including non-enhancer mediated mechanisms of insertional mutagenesis.

The symposium, entitled “Retroviral and Lentiviral Vectors for Long-Term Gene Correction: Clinical Challenges in Vector and Trial Design,” will be held December 9–10, 2010 in Bethesda, Maryland. The meeting is open to the public and free of charge. A draft agenda can be found here ⁴ .

NIH Launches Genotype-Tissue Expression Project

The National Institutes of Health has launched an initiative to understand how genetic variation may control gene activity and its relationship to disease. Launched as a pilot phase, the Genotype-Tissue Expression (GTEx) aims to provide to the scientific community a resource with which to study human gene expression and regulation and its relationship to genetic variation. This project will collect and analyze multiple human tissues from donors who are also densely genotyped, to assess genetic variation within their genomes. By analyzing global RNA expression within individual tissues and treating the expression levels of genes as quantitative traits, variations in gene expression that are highly correlated with genetic variation can be identified as expression quantitative trait loci, or eQTLs.

According to NIH Director, Dr. Francis Collins, "GTEx will begin to provide researchers with a comprehensive view of genetic variation and a more precise understanding of how it affects genes critical to the normal function of tissues and organs. This resource will add a new dimension to our understanding of human biology and the mechanisms that lead to disease ¹ ."

The initial phase of GTEx will test the feasibility of collecting high-quality ribonucleic acid (RNA) from 30 to 50 tissue sites in the body, including the brain, lung, heart, and muscle. Samples will come from approximately 160 deceased donors identified through autopsy or organ and tissue transplant programs. In addition, a small subset of normal tissues will be collected from living surgery patients as a comparison group. Extensive clinical and medical information for all GTEx donors will also be collected.

The GTEx pilot project comprises three biospecimen source sites, and a laboratory data analysis and coordinating center. Led by the National Cancer Institute's cancer Human Biobank (caHUB), http://cahub.cancer.gov/initiative, the biospecimen source sites will recruit donors and collect the tissues. (sk)