Savient Pharmaceuticals announces filing of KRYSTEXXA BLA resubmission on track

Jan 9 2010

Savient Pharmaceuticals, Inc. (Nasdaq: SVNT) provided an update on its activities directed toward the resubmission of its Biologics License Application (BLA) for KRYSTEXXA(TM) (pegloticase) as a treatment for chronic gout in patients refractory to conventional therapy and reaffirmed its belief that it continues to be on track for the filing of the BLA resubmission for KRYSTEXXA in the first quarter of 2010.

The Company announced that:

• It has completed the reversion to the manufacturing processes used to manufacture its pegloticase active pharmaceutical ingredient (API) drug substance for the pivotal Phase 3 clinical trials which the Company had committed to pursue during the September 2009 Type "A" meeting as its plan to address the concerns raised by the Food and Drug Administration (FDA) in the July 31, 2009 complete response letter. Three consecutive batches of pegloticase API drug substance were manufactured in late October 2009 at the Company's third party contract manufacturer (CMO) and were then manufactured into final KRYSTEXXA drug product in November 2009. All batches were placed on stability testing by early December 2009. This manufacturing process reversion included the successful return to the PEGylation concentration utilized in the manufacture of pegloticase API for the pivotal replicate Phase 3 clinical trials.

• The Company has received from its third party testing laboratories the majority of the in-process and final release analytical test results performed on the three consecutive batches of pegloticase API drug substance and final drug product. These analytical tests are necessary to validate these batches as being comparable to the drug product used in the Phase 3 clinical trials to establish the safety and efficacy of the drug product for the treatment of gout in patients refractory to conventional therapy. The Company believes that the analytical results to date demonstrate that the manufacturing process is consistent and that the drug substance and drug product produced in this validation campaign is comparable to the material used in the KRYSTEXXA Phase 3 clinical trials. The Company does not believe that the remaining pending analytical tests will alter their current view with respect to the success of the validation campaign and expects to receive these remaining analytical test results from its third party testing laboratories well in advance of its planned resubmission filing.

• The Company's CMO has submitted to the FDA in late December 2009 comprehensive reports and documentation of the steps that they have completed to date with the goal of addressing deficiencies and other observations that have been identified by the FDA. In addition, although not required by the FDA, the submissions by the Company's CMO included their plans and framework for implementing a broad continuous quality improvement plan.

• The safety update data to be included in the BLA resubmission demonstrates a continuing safety profile similar to that seen in the Phase 3 clinical trials. This safety update includes data from the Open Label Extension Study of KRYSTEXXA through the end of September 2009. Ninety five patients were exposed to KRYSTEXXA for at least 18 months and 63 patients were exposed for between 24 and 30 months. In particular, the Company observed no new safety concern signals and there was no evidence of any adverse change in the cardiovascular safety profile or evidence of cumulative toxicity when compared to the data provided in the original BLA or subsequent 120-day safety update to the BLA.

The Company conducted the manufacturing validation campaign following a Type "A" meeting held with the FDA in September 2009 at which the FDA indicated that, in its view, Savient's plan to revert to and validate the original manufacturing process used to produce KRYSTEXXA drug product for the Phase 3 clinical trials, together with certain process revisions such as the inclusion of additional 0.22 micron filters in the manufacturing process, was a reasonable approach that is expected to produce pegloticase API drug substance that is representative of that used to establish safety and efficacy in the pivotal Phase 3 clinical trials. The Company does not expect further clinical trials to be required provided that when the BLA resubmission is reviewed, the FDA does not observe any significant differences in their assessment of comparability results.

The complete response letter also required correction of deficiencies and observations cited by the FDA during its June 2009 pre-approval inspection of the facilities of the Company's CMO. While remediation of the deficiencies and observations arising from the FDA pre-approval inspection had been underway since the June 2009 inspection in accordance with two work plans submitted to the FDA by the CMO in June and July 2009, in October 2009 the FDA provided notification that these original work plans were not adequate and identified additional corrective actions that would be required to successfully remediate the deficiencies and observations noted in their facility, and since October 2009, the CMO has been addressing additional chemistry and manufacturing controls issues with their facility. The reports submitted to the FDA by the Company's CMO in December 2009 detail the remediation steps they have taken to date, additional actions that are currently underway and the plans and programs designed with the goal of remediating the deficiencies and observations cited by the FDA and providing the FDA appropriate comfort with the facility's compliance with current good manufacturing practices, though the FDA may not agree. The FDA may require a reinspection of the manufacturing facility of the Company's CMO as part of its consideration of the KRYSTEXXA BLA resubmission, and that reinspection could result in additional concerns being raised by the FDA. It is also possible that the FDA could require the Company to repeat its manufacturing validation campaign once the FDA determines that the Company's CMO has resolved all of these issues to the satisfaction of the FDA, though Savient does not expect the FDA to take this step.

Based on the progress made to date, the Company believes that it continues to be on track for the filing of the BLA resubmission for KRYSTEXXA within the first quarter of 2010. The resubmission will include all data requested by the FDA with respect to the manufacturing issues identified in the complete response letter and the integrated safety update, as well as drafts of prescribing information and product labeling, REMS program materials and a Medication Guide, which the Company believes are all consistent with the comments provided by the FDA in the complete response letter received by the Company on July 31, 2009 or during the September Type "A" meeting. When resubmitted, Savient expects the BLA to be subject to a Class 2 resubmission review cycle meaning an FDA decision on an action with respect to all components of the BLA resubmission would be expected within six months of the date of the resubmission.