Glybera

Glybera^® (alipogene tiparvovec) overview

Glybera has been developed for the treatment of lipoprotein lipase deficiency (LPLD), a very rare inherited condition that is associated with increased levels of chylomicrons, particles carrying certain fat in the blood. LPLD is caused by alterations in the gene that codes for a protein called lipoprotein lipase (LPL). The LPL protein has an important role in dealing with the fats from the food that we eat. When the LPL protein does not work properly, or there is not enough of it, fat levels in the blood increase dramatically.

Glybera introduces a normal, healthy LPL gene into the body so that it can make functional LPL protein. The LPL gene is packaged in a delivery vector derived from adeno-associated virus (AAV), serotype 1, which has a natural propensity towards muscle cells. As muscle cells are normally the most important tissue contributing to healthy LPL protein production, this particular AAV is very suitable for correction of LPLD. Glybera is administered via a one-time series of small intramuscular injections in the legs.

Glybera Clinical Data

Glybera has been tested in three interventional clinical studies conducted in the Netherlands and in Canada, in which a total of 27 LPLD patients were administered the therapy. One follow-up study is still ongoing. In one of the studies postprandial chylomicron metabolism was studied. In addition, a case note review study of historical data on hospital presentations due to abdominal pain from 17 patients already treated with Glybera and 5 untreated LPLD patients has been concluded.

In all studies conducted the therapy proved to be well tolerated and no material safety concerns were observed. Data from the clinical trials indicates that fat concentrations in blood were reduced after therapy in nearly all patients between 3 and 12 weeks after injection of Glybera. A single dose administration of Glybera resulted in a long-term presence and biological activity of the protein in the injected muscle. Importantly, a single administration of Glybera® resulted in a long-term, clinically important reduction in the occurrence of acute pancreatitis episodes – which represent the most debilitating complication of LPLD. The case note review study showed a significant reduction in the frequency of hospital presentations for pancreatitis and severe abdominal pain related to the pancreas. Chylomicron metabolism, poor prior to Glybera administration, proved to be much improved at 14 and 52 weeks after one-time Glybera administration, indicating sustained LPL activity in blood, which could be taken as a marker of efficacy.

Glybera Regulatory Status EU

On 23 June 2011, the Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion, recommending the refusal of the marketing authorisation for Glybera, intended for use in patients with lipoprotein lipase deficiency. AMT subsequently requested a re-examination of the negative opinion. Because Glybera is an advanced therapy medicine, it was also assessed by the Committee for Advanced Therapies (CAT). During the re-examination, the CAT concluded that the concerns from the initial CAT review could be addressed with additional post-marketing studies. Whilst the CHMP still considered Glybera to be potentially valuable in the treatment of this very rare disease, it took a different view than the CAT and concluded on October 21, 2011 that the benefits of the medicine did not outweigh its risks due to questions over the medicine’s benefits. The initial recommendation that Glybera should not be granted marketing authorisation was therefore maintained by the CHMP.

 

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THE MATERIALS YOU ARE SEEKING TO ACCESS ARE BEING MADE AVAILABLE ON THIS WEBPAGE BY AMSTERDAM MOLECULAR THERAPEUTICS (AMT) HOLDING N.V. IN GOOD FAITH AND FOR INFORMATION PURPOSES ONLY. THE MATERIALS CONTAINED HEREIN ARE NOT FOR RELEASE, PUBLICATION OR DISTRIBUTION, DIRECTLY OR INDIRECTLY, IN WHOLE OR IN PART, OR DIRECTED AT OR ACCESSIBLE BY PERSONS LOCATED IN THE UNITED STATES OR ANY OTHER JURISDICTION WHERE TO DO SO WOULD CONSTITUTE A VIOLATION OF THE RELEVANT LAWS OR REGULATIONS OF SUCH JURISDICTION.

Please read this notice carefully - it applies to all persons who view this webpage. Please note that the disclaimer set out below may be altered or updated. You should read it in full each time you visit the site.

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Viewing the materials made available on this website may not be lawful in certain jurisdictions. In other jurisdictions, only certain categories of person may be allowed to access such materials. Any person resident outside the Netherlands who wishes to access these materials must first satisfy themselves that they are not subject to any local requirements that prohibit or restrict them from doing so.

The materials made available on this website do not contain, constitute or form part of, and should not be construed as, an offer, or the invitation or solicitation to subscribe for or purchase any securities ("Securities") mentioned in the materials and nothing contained herein shall form the basis of, or be relied on in connection with, any offer or commitment whatsoever.

The Securities have not been (nor will be) registered under the US Securities Act of 1933, as amended (the "US Securities Act"), or the securities laws of any state or other jurisdiction of the United States, and may not be offered, sold, resold, taken up, exercised, renounced, transferred or delivered, directly or indirectly except pursuant to an exemption from, or in a transaction not subject to, the registration requirements of the US Securities Act.

No Securities will be offered or allotted directly or indirectly into, or by use of the mails of, or by any means or instrumentality of interstate or foreign commerce of, or any facilities of a national securities exchange of, the United States, unless an exemption from registration under the US Securities Act, is available. This includes, but is not limited to, facsimile transmission, electronic mail, telephone and the internet. Accordingly, copies of materials made available on this website and any related documents will not and must not be mailed or otherwise transmitted, distributed or forwarded in or into the United States.

The materials contained herein have not been submitted to or reviewed by the US Securities and Exchange Commission (the "SEC") or any state securities commission of any other jurisdiction, and neither the SEC nor any such state securities commission of any other jurisdiction has (a) approved or disapproved, (b) passed upon the merits or fairness of, or (c) passed upon the adequacy or accuracy of the disclosure of any materials contained herein. Any representation to the contrary is a criminal offence in the United States.

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