Krystexxa, a potential therapy for treatment-failure gout patients

[Admin]

Press Release:
Savient Pharmaceuticals gets $31M injection

Savient Pharmaceuticals Inc. (Nasdaq: SVNT) , a specialty biopharmaceutical company in East Brunswick, raised $31 million through a direct offering of shares.
The company said select new and existing institutional investors agreed to purchase 5.93 million units at $5.23 each. Each unit consists of one share of common stock and one warrant to purchase 0.85 shares of common stock. The names of the institutional investors were not disclosed.

Lazard Capital Markets LLC is the placement agent for the offering, which is slated to close by April 8.

Savient said the exercise price of the warrants is $10.46. That price may change, though, based on the Food and Drug Administration’s response to the company’s biologics license application for Krystexxa, a potential therapy for treatment-failure gout patients. These are gout patients who have not responded to other forms of treatment aimed at normalizing uric acid levels.

[Admin]

Press Release:
Gout treatment fails to win approval

WASHINGTON - Savient Pharmaceuticals Inc., a money-losing biotechnology company whose only drug lost patent protection in 2006, has failed to win US approval to sell a new gout treatment because regulators need more information.

The Food and Drug Administration issued a so-called complete-response letter, raising issues including the manufacturing process for the medicine, Krystexxa, and guidelines on evaluating its safety and efficacy, the company said.

While 3 million Americans have gout, this drug was developed for the tens of thousands whose disease does not respond to conventional therapy.

Gout is a form of arthritis in which deposits of uric acid build up around joints, causing pain, swelling, and stiffness. It was historically known as a disease of kings because obesity, alcohol, and protein-rich diets increase the risks.

Krystexxa is derived from an animal hormone that rids the body of uric acid by converting it into a form that is easily excreted.

“We are committed to work diligently to address these issues with a goal of obtaining final approval,’’ Savient president Paul Hamelin said in a prepared statement.

The company expects to complete its resubmission in early 2010, Hamelin said. East Brunswick, N.J.-based Savient said it plans to request a meeting with the FDA to discuss and clarify the issues in the regulator’s response.

Savient must include an update of safety data from all ongoing studies in its refiling, the company said in the statement. An inspection report of the drug-substance manufacturing plant is also required, it said.

An FDA advisory panel voted 14 to 1 in favor of approval of Krystexxa, also known as pegloticase, on June 16

Press Release:
Savient Pharmaceuticals Receives Complete Response Letter from U.S. Food and Drug Administration for KRYSTEXXA(TM)

EAST BRUNSWICK, N.J., Aug 02, 2009 /PRNewswire-FirstCall via COMTEX News Network/ -- Savient Pharmaceuticals, Inc. (Nasdaq: SVNT) today announced that the Company has received a complete response letter from the U.S. Food and Drug Administration (FDA) stating that the FDA can not at this time approve the Company's Biologics License Application (BLA) for KRYSTEXXA(TM) (pegloticase) as a treatment for chronic gout in patients refractory to conventional therapy.

The complete response letter from the FDA cites deficiencies with the chemistry, manufacturing and controls (CMC) section of the BLA and also provided the current draft of the proposed labeling and further guidance regarding a Risk Evaluation and Mitigation Strategy (REMS) (Medication Guide and Communication Plan). The Company intends to immediately request a meeting with the FDA to discuss and clarify the issues raised in the complete response letter. Under FDA regulations, the Company believes that this meeting is deemed a "Type A" meeting, meaning that the FDA would meet with the Company within 30 days of its receipt of the meeting request.

One of the issues raised by the FDA in the complete response letter addresses a change made by the Company in the proposed process for manufacturing KRYSTEXXA for commercial use. The FDA has 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 3 clinical trials. The FDA stated that the Company has the option of either reverting to and validating the manufacturing process used to produce KRYSTEXXA for the Phase 3 clinical trials or conducting additional comparability clinical trials to support the use of KRYSTEXXA manufactured using the proposed commercial manufacturing process. The Company currently expects that it will seek to address this issue by reverting to and revalidating the manufacturing process used to produce KRYSTEXXA for the Phase 3 clinical trials.

The complete response letter also stated that the FDA has determined that a REMS is necessary for KRYSTEXXA consisting of:

-- A Medication Guide to ensure the safe and effective use of KRYSTEXXA by
patients,
-- A Communication Plan directed to healthcare providers likely to
prescribe KRYSTEXXA to support the dissemination of information about
the risks of severe infusion reactions and possible anaphylaxis, the
risk of severe adverse reactions in administering KRYSTEXXA to patients
with glucose-6-phopshate dehydrogenase (G6PD) deficiency and major
cardiovascular events, and

-- An Assessment Plan to monitor and assess the effectiveness of the
Medication Guide and Communication Plan in communicating to patients and
physicians an understanding of the risks of KRYSTEXXA treatment.

The complete response letter included additional CMC comments focused on tightening manufacturing parameters and narrowing analytical specifications associated with commercial production. The Company was also informed that its resubmission to the FDA in response to the complete response letter must include an update of safety data from all on-going studies. Additionally, the Company's drug substance manufacturer BTG-Israel has already provided a work plan to remediate observations arising from the FDA pre-approval inspection of BTG-Israel's manufacturing facility and 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."

The Company believes that its resubmission will respond to all of the deficiencies cited in the compete response letter and would lead to a new Prescription Drug User Fee Act expected action date of either two or six months after the date of the Company's resubmission, depending on the FDA's classification of the resubmission.

[Admin]

Press Release:
Company Confirms Early 2010 Target for KRYSTEXXA Resubmission

Savient Pharmaceuticals, Inc. today announced that on September 14, 2009, the Company completed a Type A meeting with the U.S. Food and Drug Administration (FDA) to discuss the Complete Response Letter (CRL) received by Savient on July 31, 2009 regarding the Company's Biologics License Application (BLA) for KRYSTEXXA(TM) (pegloticase) as a treatment for chronic gout in patients refractory to conventional therapy.

Based on the results of this meeting with the FDA, Savient believes that the FDA supports its approach to resolve all issues cited in the CRL. The meeting also confirmed that the FDA does not expect further clinical trials to be required as a result of Savient's reversion to the original manufacturing process to produce the Phase 3 clinical trial material for KRYSTEXXA, provided that no significant differences are observed between the material produced with the validated Phase 3 process and the Phase 3 clinical trial material. Savient, therefore, continues to believe that it can meet its previously discussed timeline of filing the resubmission in response to the CRL in early 2010.

"We are encouraged by the FDA's continuing collegial and collaborative dialogue in providing guidance to assist us in establishing the path forward to our resubmission for KRYSTEXXA," stated Paul Hamelin, President of Savient Pharmaceuticals. "We are grateful to the FDA for granting us this meeting so quickly and appreciate the considerable time and effort devoted by the FDA reviewers in evaluating our pre-meeting package and in providing very valuable feedback and guidance."

In response to the CRL, Savient requested and was granted the Type A meeting with the FDA to discuss, clarify and reach alignment on a resubmission plan to fully address all deficiencies and issues identified in the CRL. The FDA indicated that, in its view, Savient's plan to revert to and validate the original manufacturing process used to produce the Phase 3 clinical trials material, together with the inclusion of additional 0.22 micron filters in the manufacturing process, is a reasonable approach that the FDA expects will produce drug substance that is representative of that used in the pivotal Phase 3 clinical trials. The FDA stated that it also expects that the comparability between material produced with the validated Phase 3 process and the Phase 3 clinical trial material used in the replicate clinical trials to establish safety and efficacy can be sufficiently established by quality criteria alone without the need to conduct additional clinical studies, provided no significant differences between products are observed.

The FDA also agreed at this meeting with the methods and criteria proposed by Savient to tighten manufacturing analytical methods and acceptance criteria for all manufacturing steps in the final commercial production process. However, some of these final analytical methods and acceptance criteria are subject to being set based upon the data from historical manufacturing and validation batches that will be included in the resubmission. The meeting outcomes confirm Savient's belief that it is on track to meet its previously discussed timeline of filing the resubmission in response to the CRL in early 2010.

The FDA also provided additional clarity relating to the steps necessary for Savient's drug substance manufacturer, Bio-Technology General (Israel) Ltd (BTG), a subsidiary of Ferring Pharmaceuticals, to satisfactorily correct the observations cited by the FDA during its pre-approval inspection of the BTG manufacturing facility. Savient believes that BTG's remediation of these observations can be corrected ahead of its resubmission to the FDA in response to the CRL.

The FDA also stated that the format and content of Savient's proposed safety update, which will include additional data collected from the KRYSTEXXA Open Label Extension study, is acceptable to the FDA.

During the meeting, the Company was informed that the review cycle for the resubmission would include the review of all data to fully address all issues identified in the CRL, including the final product labeling and the REMS materials. Since the resubmission will include REMS materials, this is subject to a Class 2 review cycle, meaning simultaneous approval of all components of our filing within six months of the date of our resubmission.

"We look forward to continuing to work with the FDA and executing on our resubmission strategy to the Complete Response Letter so that we can move forward with delivering this important therapy to treat chronic gout patients who are suffering from this crippling, debilitating disease and who have no other treatment options," commented Mr. Hamelin.

Savient also stated that the official minutes of this Type A meeting with the FDA will be made available to the Company within approximately 30 days from the date of the meeting.

Conference Call Information

Savient's management team will host a live conference call and Webcast today at 9:00 a.m. Eastern Time/6:00 a.m. Pacific Time to further discuss the results of the Type A meeting with the FDA. To participate by telephone, please dial 888-349-9587 from the U.S. or 719-457-2640 for international callers. The conference identification number is 8540659. The live and archived Webcast can be accessed on the investor relations section of the Savient Website at www.savient.com. Please log on to Savient's website 15 minutes prior to the start of the call to ensure adequate time for any downloads that may be necessary.