The FDA convened a meeting of the Endocrinologic and Metabolic Advisory Committee on January 15, 2003, to discuss the results of the clinical studies with Aldurazyme. The FDA had received a completed BLA application that included phase-3 data and 6 months of extension data, and these data were reviewed at the committee meeting primarily to assess the clinical meaningfulness of the benefit observed at the primary endpoints. In preparation, the sponsor assembled a briefing document for the panel that included a comprehensive and cogent review of the clinical data and the basis for their interpretation. Most critical to this document was the assessment of the risk-benefit profile for the product and the presentation of the product's profile within the context of the disease being studied. This was particularly important for Aldurazyme given that few physicians have had much more than a just a cursory introduction to the MPS disorders.
The main message of the briefing document from the sponsors was that MPS I was a heterogeneous and complex chronic disease with components of disease that were reversible and others that were not reversible. It is also stated that the treatment effects observed affected multiple systems within the same patients in many cases, and that the totality of the benefit from improved FVC, decreased sleep apnea, increased walk endurance, and improved range of motion must be appreciated as a synthesis of clinical benefits and within the context of a chronic disease without significant therapy.
The FDA produced a briefing document that appropriately intended to question the data and the clinical meaningfulness of the changes observed. The Advisory Committee was asked to vote on whether the change in FVC and the change in the 6-min walk test were clinically meaningful.
In addition to the briefing documents and the presentations, the advisory committee process provided an opportunity for patients on the drug and patient advocacy groups to speak during the public session. The well-prepared and thoughtful presentations by the families of patients about their experience with Aldurazyme for nearly 5 years was compelling testimony as to the value and longevity of the clinical benefit. The families focused on the specific and measurable changes they observed in their children and the importance that these changes had in specific events in their daily lives. Although a public session cannot ever replace an appropriate development plan and good clinical data, a well-prepared and well-expressed public session can be effective in helping the panel appreciate the full story as to how the drug is working from those that know it firsthand. In the case of Aldurazyme, the clinical data and the strong patient support were an important component of the information considered by the panel. The panel voted 12 to 0 that both the FVC and 6-min walk test results were clinically meaningful. Aldurazyme was approved 3 months later.
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