uniQure’s Glybera (alipogene tiparvovec) gene therapy for lipoprotein lipase deficiency (LPLD) is just one step removed from becoming the first gene therapy sanctioned in Europe or the U.S. following a recommendation of approval for its use, though only under exceptional circumstances, by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP). If the European Commission decides to go with the recommendation and sanction Glybera, a registry will have to be set up to monitor patient outcomes, and results reported back to the EMA.

Although the EC could still refuse to approve the drug, uniQure remains optimistic that regulatory clearance is now just matter of time. “We expect final approval from the EC within three months after the CHMP decision,” comments Jörn Aldag, uniQure CEO. “After today’s positive recommendation, Glybera is poised to become the first in a class of gene therapy products approved in Europe to treat orphan diseases.”

CHMP’s recommendation of approval for Glybera is a complete turnaround from the negative opinions metered out by the committee over more than a year. “The evaluation of this application has been a very complex process, but the use of Glybera in a more restricted indication than initially applied for, which targets the patient population with greatest need for treatment, and additional analyses by the Committee for Advanced Therapies (CAT), have added to the robustness of the data provided and allowed the CHMP to conclude that the benefits of Glybera are greater than its known risks,” states Tomas Salmonson, M.D., acting chair of the CHMP.

“Our established ways of assessing the benefits and risks of Glybera were challenged by the extreme rarity of the condition and also by uncertainties associated with data provided. In close cooperation with the CAT we have worked out a way to ensure robust and close follow-up of the quality, safety, and efficacy of Glybera while giving patients who have to live with this rare disease access to a medical treatment.”

Getting Glybera successfully through CHMP scrutiny has not only been a real battle, but ultimately ended up in the demise of Amsteram Molecular Therapeutics, which originally developed the gene therapy. In early April AMT’s assets were passed on to uniQure, a firm established to take on the AMT gene therapy technologies and pipeline. For most of the last year, however, AMT had battled to overturn CHMP’s repeated recommendation against approving Glybera on risk/benefit grounds. This continued refusal to recommend was reiterated despite a positive recommendation by the expert Scientific Advisory Group for the product, and the EMA’s Committee for Advanced Therapies (CAT), which concluded that any concerns could be addressed by postmarketing studies. The last nonapproval recommendation by CHMP was in April, and was particularly cruel given that its members voted of 16–15 in favor of recommending Glybera. Unfortunately, at least 17 positive votes are required to enable a positive recommendation. Fewer than 17 means a negative opinion has to be recorded.

“CAT has worked closely with the CHMP throughout the procedure,” adds Christian Schneider, M.D., the committee’s chair. “I was concerned about reports in the public domain of differences between the two committees during the approval process, since the scientific assessment of the CAT and the CHMP were not far apart. The dossier is maybe a unique case where the ultra-rarity of the disease, its fluctuating rather than continuously progressing clinical course, and the complexity of the scientific data led to difficult scientific decision-making.”

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