Savient Receives Complete Response Letter for Gout Drug

Despite a 14-1 advisory panel recommendation, the FDA has issued a Complete Response letter to Savient Pharmaceuticals for its gout treatment Krystexxa. The letter cites deficiencies with the CMC section of Krystexxa’s BLA and also provided the current draft of the proposed labeling and further guidance regarding a Risk Evaluation and Mitigation Strategy (REMS).

Savient plans to immediately request a meeting with the FDA to discuss and clarify the issues raised in the letter. The company contends that, under FDA guidelines, this meeting is deemed a “Type A” meeting, meaning that the FDA would meet with Savient within 30 days of its receipt of the meeting request. The company plans to resubmit the BLA in early 2010.

One of the issues raised by the FDA in the complete response letter addressed a change made by the company in the proposed process for manufacturing Krystexxa for commercial use. The FDA concluded that “the comparability data submitted for the material manufactured using the proposed commercial manufacturing process was not adequate to demonstrate that it was representative of the material used to establish the safety and efficacy of KRYSTEXXA in its Phase III clinical trials,” according to a Savient statement. The agency stated that Savient has the option of either reverting to and validating the manufacturing process used to produce Krystexxa for the Phase III trials or conducting additional comparability clinical trials to support the use of Krystexxa manufactured using the proposed commercial manufacturing process. Savient currently expects to revert to and revalidate the earlier manufacturing process.

The letter included additional CMC comments focused on tightening manufacturing parameters and narrowing analytical specifications associated with commercial production. Savient will also have to include an update of safety data from all ongoing studies when it resubmits its BLA.

Savient’s drug substance manufacturer, BTG-Israel, has provided a work plan to remediate observations arising from the FDA pre-approval inspection of its manufacturing facility. A satisfactory inspection report is required prior to the approval of Krystexxa.

“While our timeline for resubmission to the FDA is subject to a number of uncertainties, we currently believe that we can target completion of our resubmission for early 2010. We hope to have more clarity on the expected timeline after we meet with the FDA to discuss the complete response letter,” stated Paul Hamelin, president of Savient Pharmaceuticals. “While we believe we have made substantial progress toward the potential final approval of Krystexxa, we also have more work to do with the FDA to resolve these open issues. We are committed to work diligently to address these issues with a goal of obtaining final approval for Krystexxa so we can provide this therapy to those chronic gout patients who are suffering from this crippling, debilitating disease and have no other treatment options.”

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