By James DeGiulio --
Last year we reported that gene therapy was experiencing a revival of sorts, now that many of the safety concerns raised from early clinical trials have been resolved (see "Gene Therapy Experiencing a Revival"). However, this revival has not yet produced marketable therapeutics, as the FDA has yet to approve a gene therapy therapeutic in the U.S., and in March 2010, the European Medicines Agency (EMA) rejected Europe's first filed gene therapy application. Expectations in the field were that Amsterdam Molecular Therapeutics' (AMT) new Glybera therapy could very well be the first for approval -- but on June 24, AMT announced that the EMA had rejected its application for a gene therapy therapeutic for lipoprotein lipase deficiency (LPLD). AMT moved quickly and has already filed an application for re-examination. However, the reward for the first approved gene therapy therapeutic in a registered market remains unclaimed.
Glybera (alipogene tiparvovec) was developed as a treatment for the rare genetic disorder LPLD. Because of a defective gene, LPLD patients do not produce an enzyme that normally breaks down a certain type of fat carrying particles in the blood. Glybera uses an adeno-associated virus (AAV) vector that carries a gene for lipoprotein lipase, which restores the enzyme's activity required to process the fat carrying particles. LPLD patients have extremely high fat levels in their blood, resulting in recurrent and potentially lethal pancreatitis as well as an increased risk of cardiovascular complications and diabetes. Currently, there exists no effective treatment or cure for the serious disease.
The EMA told AMT that it has not provided enough evidence of the long-term efficacy of the product. LPLD is an extremely rare condition, and the clinical trial data submitted to EMA for approval included only 27 patients. The EMA said at present there are too few patients for whom sufficiently long-term data were available, and as a result, there was insufficient evidence of a reduction in the rate of pancreatitis. Importantly, the EMA did not have any concerns about the safety of Glybera, which supports an emerging inclination that the safety of gene therapy is no longer the roadblock to regulatory approval as it has been in the past. Indeed, the first gene therapy product ever to be filed for approval with EMA was Cerepro, a gene therapy for treating brain cancer, which also presented no concerns about the safety of the product. The EMA refused approval of Cerepro because there was not enough evidence that Cerepro was effective.
AMT believes it can avoid the pitfalls of Cerepro, and has already filed for re-examination of its application. AMT must now collect more data to show that there is a long-term reduction in the incidence of pancreatitis in treated patients. AMT said it will be possible to generate the additional data required from the existing treated patients, and the data will come from a trial which the company had already planned to do as a postmarketing study. AMT hopes to garner the additional data and resubmit the Glybera file by the end of 2011. In addition to its pursuit of Glybera, AMT will also continue development of other gene therapy products in the company's pipeline, such as therapeutics for Parkinson's disease and Huntington's disease. AMT is also preparing to apply for market approval of Glybera in Canada and the U.S.
Remind me why we require efficacy showings in cases like this where safety is not in debate, the patient population is small, under the care of specialists and extremely unlikely to be lead astray by patent medicine flimflam, and the health issues are life-threatening? Other than, of course, regulators sacrificing at the altar of statistics and Government health care systems apoplectic at the costs.
Posted by: max hensley | July 27, 2011 at 09:22 AM