快樂小藥師 Im pharmacist nichts glücklich

The European Medicines Agency has for the first time recommended approval of a gene therapy, for the treatment of lipoprotein lipase (LPL) deficiency. The agency's Committee for Medicinal Products for Human Use (CHMP) recommended marketing authorization under "exceptional circumstances" for alipogene tiparvovec (Glybera, uniQure). The drug was designated an "orphan medicine" on March 8, 2004, and is recommended for use in a restricted group of adults with familial LPL deficiency who have severe or multiple pancreatitis attacks despite dietary fat restrictions.

歐洲藥品管理局EMA批准了首例基因療法藥物

這種基因療法藥物主要適用於那些患有脂蛋白脂酶缺乏(lipoprotein lipase deficiency )的患者，脂蛋白酯酶缺乏是一種極為罕見的遺傳缺陷病。患有脂蛋白脂酶缺乏症之後，患者體內的血液無法承受任何脂肪顆粒，而且這類患者在飲食方面禁食正常餐飲，因為患者容易出現各種急性胰腺癌病症。

　　脂蛋白脂酶缺乏(lipoprotein lipase deficiency )病症十分罕見，每百萬人中約有一到兩例患者，這種症狀極易引致急性胰腺癌甚至會導致患者死亡。

Glybera為單次注射劑，適用於嚴格限制脂肪飲食卻仍然發生嚴重或反復胰腺炎發作的脂蛋白脂酶缺乏症(LPLD)患者。

目前，唯一對LPLD患者有幫助的是採取嚴格限制脂肪飲食，使每日通過脂肪獲得的熱量不超過總熱量的20％。但要堅持這樣的飲食習慣並不容易，因此許多患者因危及生命的胰腺炎而住院。 

基因治療通過以有活性的基因取代患者DNA中有缺陷的基因而發揮療效。Glybera利用一種腺相關病毒將有活性的LPL基因插入肌細胞中，從而使這些細胞能產生正常數量的酶。

LPL deficiency is a rare genetic disease that results from a defect in the gene for LPL, an enzyme that breaks down fats. This causes excessive fat particles to accumulate in the blood, leading to pancreatitis attacks. Glybera is made from an adeno-associated viral vector (AAV1) that has been modified so that it carries a gene for LPL but does not replicate. It is injected into a muscle, where it corrects the LPL deficiency by enabling muscle cells to produce LPL.

Immunosuppressant drugs are typically given as well to reduce the immune system's response against the medication.

James Wilson, MD, PhD, a professor of pathology and laboratory medicine at the University of Pennsylvania in Philadelphia, commented on this development for Medscape Medical News. Dr. Wilson's laboratory discovered the vector (AAV) that was used. The vector is owned by the University of Pennsylvania and was licensed to another company that then provided it to the manufacturer, he explained, adding that he has no relationship with uniQure.

"What the clinical trials have shown is that the number of pancreatitis episodes are decreased, and pancreatitis can be fatal, so it's a potentially fatal disease for which it may help these patients," Dr. Wilson said.

The CHMP has worked in consultation with the European Medicines Agency's Committee for Advanced Therapies (CAT). The CHMP initially issued a negative opinion about the drug on June 23, 2011, recommending refusal of marketing authorization because of insufficient evidence of long-term benefit in the patients studied.

After re-examination in October 2011, the CAT determined that additional postmarketing studies would have adequately addressed concerns about the medication's long-term benefits, but the CHMP again recommended refusal of marketing authorization.

After a request from the European Commission, the CHMP considered the medication for use in a restricted group of patients with more severe illness, and in April 2012 the committee reiterated its position that marketing authorization should be denied.

The CHMP then decided to conduct a second evaluation of this restricted group, with input from the CAT. Several factors were considered, including data that showed a reduction in the number of pancreatitis episodes and the extreme rarity of the disease, and the CHMP concluded that the medicine's benefits outweigh the risks in patients with severe disease, a group whose medical need is largely unmet.

In addition, the committee recommended that marketing authorization be granted under exceptional circumstances, which means that the company that markets the gene therapy will need to set up a registry to monitor patient outcomes and provide ongoing data to the agency.

A restricted access program will also be in place to ensure appropriate use of the medication.

"I don't believe they have approached the [US Food and Drug Administration] yet, but I know that they're speaking to potential partners to do that," said Dr. Wilson.

"This is the first approved gene therapy product in a Western country, and I believe that it's going to be an important impetus with investors in the biopharmaceutical industry to get in the game. One of the concerns of biopharm has been regulatory uncertainty over whether a European or US regulator would actually approve a product, and what the barriers would be, and apparently this group has overcome that," said Dr. Wilson.

"I believe it's a true milestone, because the ultimate development of an emerging new technology is whether it can be commercialized, and this shows that it can, so I'm sure there will be many more," Dr. Wilson said.

Dr. Wilson has disclosed no relevant financial relationships.