After more than two decades of dashed expectations, the field of gene therapy appears close to reaching a milestone: a regulatory approval.
The European Medicines Agency, an arm of the European Union, has recommended approval of a gene therapy to treat a rare genetic disease, according to the agency’s website.
If the European Commission follows the advice, as it usually does, this would be the first regulatory approval of a gene therapy drug in the Western world. That could give a boost to the field, which at times has struggled for credibility and financing.
An approval “is really potentially going to change the way the field is looked at,” said Jeffrey Ostrove, chief executive of Ceregene, a gene therapy company in San Diego. Some pharmaceutical companies have been reluctant to invest in the field, he said, because “there are no approved products in the major markets they sell in.”
Gene therapy involves providing the body with genes it needs, such as correct copies of defective genes that cause genetic disorders. Its use in the West so far has been confined to clinical trials.
The therapy recommended for approval in Europe, called Glybera, was developed by uniQure, a Dutch company. It treats lipoprotein lipase deficiency, a disease that affects only several hundred people in the EU and a similar number in North America.
People with the disease have a genetic mutation that prevents them from producing an enzyme needed to break down certain fat-carrying particles that circulate in the bloodstream after meals. Without the enzyme, so much fat can accumulate that the blood looks white rather than red.
“It’s the equivalent of having a 10 percent cream in your bloodstream,” said Dr. Daniel Gaudet, a professor of medicine at the University of Montreal, who led the clinical trials of the drug.
People with the disease are prone to severe bouts of inflammation of the pancreas. There is no good treatment except an extremely low-fat diet.
Glybera provides correct copies of the lipoprotein lipase gene, which allows patients to make some of the needed enzyme. A single treatment, consisting of injections into multiple spots on the leg muscles on the same day, is expected to last for several years, if not longer, said Joern Aldag, chief executive of uniQure.
Aldag said the company hoped to apply for approval of the gene therapy in the United States eventually, but he was not certain of the timing.
Gene therapy has long been seen as promising way to treat numerous diseases. But hundreds of clinical trials have been conducted since 1990 and most have failed, in part because it has been difficult to deliver the genes and get them to work for a long time. The field has also been set back by some safety issues, particularly the death of a teenager in a 1999 clinical trial at the University of Pennsylvania.
But researchers have been slowly overcoming the obstacles and in the last few years there have been reports of successes in attempts to treat cancer and hemophilia B, as well as certain immune diseases and a condition that causes blindness.
“It didn’t occur as rapidly, I think, as people had kind of promised or suggested 15 or 20 years ago, but we are starting to see success,” said Dr. Mark Kay, a professor of pediatrics and genetics at Stanford.
A gene therapy to treat cancer won approval in China in 2003. But some Western experts have questions about the rigor of the regulatory review in that country.
How effective Glybera is might still be open to some question, in part because the company tested the drug in only 27 patients, and without rigorous controlled clinical trials.
The Committee for Medicinal Products for Human Use, which recommends whether new drugs should be approved in Europe, rejected Glybera three times in the last year or so.
After its third rejection, in April, the committee said that the company had “not provided sufficient evidence” that blood lipids were lowered in a persistent manner and that there was also insufficient evidence of a reduction of the incidence of pancreatitis, the inflammation of the pancreas.
But the committee has now reversed itself. It said the approved population had been narrowed to those with the most severe disease and that the company would be required to monitor the outcomes of patients treated with Glybera and provide that data to regulators.
Gaudet, who has been a paid adviser to uniQure, said the trials showed that after the treatment, patients had fewer bouts of pancreatitis and those bouts tended to be less intense and painful.
The repeated setbacks took its toll on the company, which was once known as Amsterdam Molecular Therapeutics. That company ran out of money this year and is now being liquidated. UniQure, which is privately held, was formed with new investment and took on the people and assets of Amsterdam Molecular.