Gene Therapy Files for Approval

An estimated one thousand clinical trials have been conducted for gene therapies in the past 20 years, but to date, not a single drug has made it to FDA approval. However, we may be a step closer as Introgen today announced that it has filed applications with FDA and EMEA for marketing approval of Advexin, its new gene therapy for cancer.

The product, which grew out of research at the M.D. Anderson Cancer Center, uses a modified adenovirus to deliver the TP53 gene to cells in the tumor, causing them to express the tumor-supressing protein P53. The drug, which is delivered into the tumor by injection, recently completed a Phase III trial in end-stage head and neck cancer. In the trial, patients with the right P53 profile showed a strong response to the drug and a good safety profile.

Gene therapies have had a hard row to hoe since 1990, when the first experiments were conducted. Effectiveness was occasionaly spectacular, but safety failures, when they’ve occurred, have been pretty spectacular too. But with significant unmet need, good biomarker support, a well-understood method of action, and strong safety data, Advexin could be the drug that gets FDA to change its mind.

One way or another, gene therapies are obviously attracting a lot of attention. Here’s a small sampling of the news from just the past couple of weeks:

• Researchers speaking at the American Urological Association explained that they had treated erectile dysfunction by injecting naked copies of the Maxi-K gene directly into penile smooth muscle. Safety is currently looking good, but the researchers want to go back with a higher dose to test efficacy.
• A Phase I trial is getting under way to test Celladon’s Mydicar in severe heart failure. The treatment involves injecting the gene that expresses the enzyme SERCA2a into the hearts of patients who underproduce it.
• Amsterdam Molecular Therapeutics announced that it has finished enrolling a pivotal trial for product AMT-011 (Glybera(R: 68.11, -0.77, -1.11%)) for Hyperlipoproteinemia. The disease, which is currently untreatable, causes patients to have a defective HPL gene, and thus fail to produce a key enzyme that breaks down fats. AMT-011 uses an adeno-associated virus to deliver healthy copies of the gene to muscle tissue.
• An Australian researcher who had previously controlled hemophilia with gene therapy, only to have the immune system undo his work far too quickly, announced that he would launch a clinical trial by the end of the year to see if he could use immunosuppression to get the body to accept the new genes.
• And finally, in a sign of just how close some observers think we are to practical gene therapy, sports officials announced that they are already on the lookout for “gene doping,” the latest, and as yet entirely hypothetical form of illegal performance enhancement.