Savient Pharmaceuticals Announces Publication of Pivotal Phase III Krystexxa Data in JAMA Demonstrating Significant Benefits in Refractory Chronic Gout Patients

-- Pooled data from two Phase III studies demonstrated that 42 percent of refractory chronic gout (RCG) patients treated with KRYSTEXXA every two weeks achieved statistically significant reductions in uric acid levels that were sustained for at least 6 months, compared to zero percent of RCG patients on placebo

-- Results also showed that a statistically significant 40 percent of RCG patients with tophi who received KRYSTEXXA every two weeks experienced complete resolution of one or more tophi, compared to seven percent of patients on placebo

-- Improved patient-reported outcomes in physical function, pain and quality of life were also observed in KRYSTEXXA-treated patients

-- KRYSTEXXA is the first and only FDA-approved treatment for RCG

EAST BRUNSWICK, N.J., Aug. 16, 2011 /PRNewswire/ -- Savient Pharmaceuticals, Inc. (NASDAQ: SVNT) today announced that results from two pivotal KRYSTEXXA® (pegloticase) Phase III clinical studies in patients with refractory chronic gout (RCG) have been published in The Journal of the American Medical Association (JAMA). The data demonstrated that treatment with KRYSTEXXA resulted in significant and sustained reductions in uric acid levels along with clinical improvements in a substantial proportion of RCG patients for six months, a timeframe for demonstrating clinical improvement that is unique in randomized controlled studies of urate-lowering therapies.

The two replicate, randomized, double-blind, placebo-controlled Phase III studies were designed to evaluate the efficacy and tolerability of treatment with KRYSTEXXA 8 mg every two weeks or every four weeks compared to placebo for the management of RCG patients. Pooled results from these studies demonstrated that treatment with KRYSTEXXA every two weeks, the U.S. Food and Drug Administration (FDA)-approved dose, resulted in a statistically significant and sustained reduction in uric acid levels below 6 mg/dL in 42 percent of patients, compared to zero percent of patients receiving placebo (p<0.001).

In addition, 40 percent of patients with tophi receiving KRYSTEXXA every two weeks experienced complete resolution of one or more tophi, which are deposits of crystalline urate in joints, skin or cartilage, by the final study visit, compared to seven percent of patients on placebo (p=0.002). A tophus complete response was defined as 100 percent reduction in the measured area of at least one tophus without growth of any baseline tophus or appearance of any new tophus.

"When effective lowering of uric acid levels cannot be achieved with oral medications, many gout patients progress to a severe form of the condition known as refractory chronic gout, which is characterized by frequent arthritic flares, chronic pain, physical disability and poor quality of life," said Michael A. Becker, M.D., Professor Emeritus of Medicine at The University of Chicago. "The data from these studies demonstrated that significant and rapid clinical benefits can be shown in such severely affected patients during KRYSTEXXA treatment."

Improved patient-reported outcomes in physical function, pain and quality of life were also observed in KRYSTEXXA-treated patients.

"The availability of KRYSTEXXA has brought hope to refractory chronic gout patients who have not responded to conventional therapies and is the first and only FDA approved treatment for RCG," said John H. Johnson, Chief Executive Officer and President of Savient Pharmaceuticals. "We are proud to have results from the Phase III clinical program published in a prestigious peer-reviewed journal, which further demonstrates that KRYSTEXXA represents an important advancement in the treatment of this severe and debilitating disease."

The most commonly reported adverse events, occurring in at least five percent of KRYSTEXXA-treated patients, were gout flare, infusion reaction, nausea, contusion or ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis and vomiting. During the first three months of treatment, the incidence of gout flares was higher in patients treated with KRYSTEXXA every two weeks compared to placebo; however, with continued treatment during months four through six, reductions in gout flares were observed in the proportion of patients with gout flare in the KRYSTEXXA every two-week versus placebo-treated groups.

Infusion-related reactions (IRs) occurred in 26 percent, 42 percent and five percent of the every two-week, every four-week and placebo-treated study groups, respectively. Resolution of all IRs began within minutes of slowing or discontinuing the infusion and/or initiating supportive treatment, and all IRs resolved completely.

In a retrospective analysis of IRs, five patients experienced anaphylaxis, including two patients each in the KRYSTEXXA every two-week and every four-week cohorts, and one additional patient assigned every two-week treatment who experienced anaphylaxis during the first infusion. All signs and symptoms resolved completely in these five patients, and three of these patients continued participating in the studies and receiving treatment with KRYSTEXXA.

As previously reported, seven deaths occurred between randomization and database closure in the KRYSTEXXA clinical development program; however, none were believed to be drug related. Four deaths occurred in the treatment group and three occurred in the placebo group. Of the four deaths in the treatment groups, two were attributed to cardiac events and occurred in patients with four or more cardiovascular risk factors at baseline. Of the two non-cardiovascular related deaths, one was attributed to renal failure after the patient's voluntary withdrawal from renal dialysis, and the other was attributed to methicillin-resistant Staphylococcus aureus sepsis.

ABOUT THE KRYSTEXXA® PIVOTAL STUDIES

The two replicate, randomized, six-month, double-blind, placebo-controlled KRYSTEXXA® Phase III trials were conducted in centers in the United States (U.S.), Canada and Mexico between June 2006 and October 2007 and evaluated 212 patients with severe gout, allopurinol intolerance/refractoriness, and serum uric acid concentration > 8.0 mg/dL. Patients were randomly assigned to receive 12 two-week intravenous infusions containing either KRYSTEXXA 8 mg at each infusion every two-weeks or KRYSTEXXA alternating with placebo at successive infusions (every four-week treatment group) or placebo (every two-week placebo group).

ABOUT KRYSTEXXA®

KRYSTEXXA® (pegloticase) is a PEGylated uric acid specific enzyme for administration by intravenous infusion for the treatment of refractory chronic gout (RCG) in adult patients. KRYSTEXXA became commercially available in the U.S. by prescription on December 1, 2010, and is the only U.S. Food and Drug Administration approved product specifically indicated for the treatment of RCG. KRYSTEXXA is not recommended for the treatment of asymptomatic hyperuricemia. For more information about KRYSTEXXA, please visit: http://www.krystexxa.com/.

IMPORTANT SAFETY INFORMATION ABOUT TREATMENT WITH KRYSTEXXA®

KRYSTEXXA is not indicated for the treatment of asymptomatic hyperuricemia. Patients who are at risk of having a condition known as G6PD deficiency should be screened by their physician prior to starting therapy with KRYSTEXXA.

Possible side effects of KRYSTEXXA include:

Anaphylaxis which occurred in some patients treated with KRYSTEXXA. KRYSTEXXA should be administered in healthcare settings and by healthcare providers prepared to manage anaphylaxis. Patients should be pre-medicated with antihistamines and corticosteroids. Patients should be closely monitored for an appropriate period of time for anaphylaxis after administration of KRYSTEXXA.


Infusion reactions which occurred in some patients treated with KRYSTEXXA. The risk of an infusion reaction is higher in patients who have lost therapeutic response. Because the risk of infusion reactions is higher in patients who lose therapeutic response to KRYSTEXXA, monitor serum uric acid before each infusion and consider discontinuing treatment if levels rise above 6mg/dL, particularly when two consecutive levels above 6 mg/dL are observed.


As with other urate-lowering therapies, an increase in gout flares was seen in some patients treated with KRYSTEXXA. Gout flare prophylaxis with a non-steroidal anti-inflammatory drug (NSAID) or colchicine is recommended starting at least 1 week before initiation of KRYSTEXXA therapy and lasting at least 6 months, unless medically contraindicated or not tolerated.


KRYSTEXXA has not been formally studied in patients with congestive heart failure, but some patients in clinical trials experienced exacerbation. Exercise caution when using KRYSTEXXA in patients who have congestive heart failure and monitor patients closely following infusion.

Patients receiving re-treatment may be at increased risk for anaphylaxis and infusion reactions and should be monitored carefully.

ADVERSE REACTIONS

The most commonly reported serious adverse reactions are anaphylaxis, infusion reactions and gout flares. Most common adverse reactions: gout flares (77%), infusion reactions (26%), nausea (12%), contusion or ecchymosis (11%), nasopharyngitis (7%), constipation (6%), chest pain (6%), anaphylaxis (5%), and vomiting (5%).

Please see the Full Prescribing Information and Medication Guide at http://www.krystexxa.com/.

ABOUT REFRACTORY CHRONIC GOUT

Gout is a painful, debilitating form of arthritis and affects approximately eight million people in the U.S. alone. A significant sub-population of gout patients, approximately 120,000, are burdened with a difficult-to-treat form of the condition, known as refractory chronic gout (RCG). Symptoms of gout are caused by the body's response to the presence of uric acid crystals in the joints and surrounding tissue, which form when uric acid levels in the blood are elevated (a condition called hyperuricemia). The longer hyperuricemia persists, the higher the risk of developing gout. Symptoms of gout may include painful flares, pain or swelling in the joints (known as "gouty arthritis") or deposits of uric acid crystals under the skin, called "tophi." In cases of RCG, these symptoms may have a major influence on patient health-related quality of life due to the frequency and severity of episodes, the recurrent pain and the disfigurement associated with this condition. Although most cases of gout can be controlled with conventional urate-lowering therapy, when uric acid levels remain high and symptoms persist despite treatment efforts, chronic gout may be defined as refractory.

ABOUT SAVIENT PHARMACEUTICALS, INC.

Savient Pharmaceuticals, Inc. is a specialty biopharmaceutical company focused on developing and commercializing KRYSTEXXA® (pegloticase) for the treatment of chronic gout in adult patients refractory to conventional therapy. Savient has exclusively licensed worldwide rights to the technology related to KRYSTEXXA and its uses from Duke University ("Duke") and Mountain View Pharmaceuticals, Inc. ("MVP"). Duke developed the recombinant uricase enzyme and MVP developed the PEGylation technology used in the manufacture of KRYSTEXXA. MVP and Duke have been granted U.S. and foreign patents disclosing and claiming the licensed technology and, in addition, Savient owns or co-owns U.S. and foreign patents and patent applications, which collectively form a broad portfolio of patents covering the composition, manufacture and methods of use and administration of KRYSTEXXA. Savient also manufactures and supplies Oxandrin® (oxandrolone tablets, USP) CIII in the U.S. For more information, please visit the Company's website at www.savient.com.

FORWARD-LOOKING STATEMENTS

All statements other than statements of historical facts included in this press release are forward-looking statements that are subject to certain risks, trends and uncertainties that could cause actual results and achievements to differ materially from those expressed in such statements. These risks, trends and uncertainties are in some instances beyond our control. Words such as "anticipate," "believe," "estimate," "expect," "intend," "plan," "will" and other similar expressions identify forward-looking statements, although not all forward-looking statements contain these identifying words. In particular, any statements regarding the safety and efficacy of KRYSTEXXA®, status of our KRYSTEXXA® marketing efforts and additional plans related thereto, market demand and reimbursement for KRYSTEXXA, our view of the refractory chronic gout (RCG) market size based on the completion of our recent comprehensive study, and our market expansion plans including our MAA filing before the EMA are forward-looking statements. These forward-looking statements involve substantial risks and uncertainties and are based on our assessment and interpretation of the currently available data and information, current expectations, assumptions, estimates and projections about our business and the biopharmaceutical and specialty pharmaceutical industries in which we operate. Important factors that may affect our ability to achieve the matters addressed in these forward-looking statements include, but are not limited to, our ability to commercialize KRYSTEXXA®; the risk that the market for KRYSTEXXA is smaller than we have anticipated; our ability to retain the personnel whom we have hired and to hire the remaining personnel necessary to complete the build out of our commercial team; our reliance on third parties to manufacture KRYSTEXXA; competition from existing therapies and therapies that are currently under development, including therapies that are significantly less expensive than KRYSTEXXA; our ability to gain market acceptance for KRYSTEXXA among physicians, patients, health care payers and others in the medical community; whether we are able to obtain financing, if needed; economic, political and other risks associated with foreign operations; risks of maintaining protection for our intellectual property; risks of an adverse determination in intellectual property litigation; and risks associated with stringent government regulation of the biopharmaceutical industry and other important factors set forth more fully in our reports filed with the Securities and Exchange Commission, to which investors are referred for further information. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements, which speak only as of the date of publication of this press release. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. Our forward-looking statements do not reflect the potential impact of any future acquisitions, mergers, dispositions, joint ventures or investments that we may make. We do not have a policy of updating or revising forward-looking statements and, except as required by law, assume no obligation to update any forward-looking statements.

SVNT-G


SOURCE Savient Pharmaceuticals, Inc.
 

Posted: August 2011

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