Kowa Pharmaceuticals America, Inc. Announces Court Decision to Uphold Patent Protection for LIVALO^® (pitavastatin calcium)

MONTGOMERY, AL, October 11, 2017 (BUSINESS WIRE) – Kowa Pharmaceuticals America, Inc. announced today that the U.S. District Court, Southern District of New York, has found that the U.S. Patent 8,557,993 (the “’993 patent") protecting LIVALO^® (pitavastatin calcium) is valid, and that generic drug manufacturer Apotex, Inc. and Apotex Corp. ("Apotex")’s proposed Abbreviated New Drug Application (ANDA) product would infringe the ‘993 patent.

Kowa Company, Ltd., Kowa Pharmaceuticals America, Inc., and Nissan Chemical Industries, Ltd. (collectively, "Plaintiffs"), manufacturers of the cholesterol-lowering drug LIVALO, brought suit against Defendants Amneal Pharmaceuticals LLC, and Apotex, Inc. and Apotex Corp., for alleged patent infringement based on the filing of the Defendants’ ANDAs seeking Food and Drug Administration (FDA) approval to market 1 mg, 2 mg, and 4 mg pitavastatin calcium tablets, generic to LIVALO. In response to these suits, the Defendants had contended that the '993 patent is invalid as (1) anticipated based on prior art, under 35 U.S.C. § 102(b); and/or (2) obvious in view of prior art, under 35 U.S.C. § 103. Only Apotex asserted non-infringement; Amneal conceded infringement.

The Court concluded that the Plaintiffs proved that Apotex's proposed ANDA product literally infringes, or contributes to the infringement of, certain claims of the '993 patent. The Court further concluded that Amneal and Apotex failed to prove invalidity of the ‘993 Patent. The Plaintiffs are directed to submit a proposed judgment by October 6, 2017.

In addition to the Court’s decision on the ‘993 patent, the Court also recently upheld the validity of another patent which covers LIVALO, U.S. Patent 5,856,336, in a separate decision in April, 2017, relating to the same trial. Both Amneal and Apotex conceded infringement of the ‘336 Patent, and Apotex conceded its validity. The Court concluded that Amneal failed to prove invalidity of the ‘336 patent. The U.S. Patent Trial and Appeal Board had also previously rejected three separate petitions by other companies for inter partes review, challenging the ‘336 Patent.

Several additional lawsuits were brought against other generic companies, all of which settled.

"We are very pleased with the Court's rulings upholding the infringement and validity of the patents for LIVALO," said Ben Stakely, Chairman, CEO and President of Kowa Pharmaceuticals America, Inc. "We look forward to continuing to supply this life-saving product to patients, and will continue to actively protect and defend our intellectual property."

Kowa Company, Ltd., Kowa Pharmaceuticals America, Inc., and Nissan Chemical Industries, Ltd. were represented by Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.

About LIVALO

LIVALO is an HMG-CoA reductase inhibitor (statin).

INDICATIONS AND USAGE

Drug therapy should be one component of multiple-risk-factor intervention in individuals who require modifications of their lipid profile. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol only when the response to diet and other nonpharmacological measures has been inadequate.

PRIMARY HYPERLIPIDEMIA AND MIXED DYSLIPIDEMIA

LIVALO (pitavastatin) is indicated as an adjunctive therapy to diet to reduce elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C) in adult patients with primary hyperlipidemia or mixed dyslipidemia.

LIMITATIONS OF USE

• Doses of LIVALO greater than 4 mg once daily were associated with an increased risk for severe myopathy in premarketing clinical studies. Do not exceed 4-mg, once-daily dosing of LIVALO
• The effect of LIVALO on cardiovascular morbidity and mortality has not been determined
• LIVALO has not been studied in Fredrickson Type I, III, and V dyslipidemias

IMPORTANT SAFETY INFORMATION FOR LIVALO^® (PITAVASTATIN) TABLETS

CONTRAINDICATIONS

LIVALO is contraindicated in patients with a known hypersensitivity to product components, in patients with active liver disease (which may include unexplained persistent elevations in hepatic transaminase levels), in women who are pregnant or may become pregnant, in nursing mothers, or in co-administration with cyclosporine.

WARNINGS AND PRECAUTIONS

Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including LIVALO. These risks can occur at any dose level, but increase in a dose-dependent manner.

• LIVALO should be prescribed with caution in patients with predisposing factors for myopathy.
• The risk of skeletal muscle effects (e.g., myopathy and rhabdomyolysis) increases in a dose-dependent manner with advanced age (≥65 years), renal impairment, inadequately treated hypothyroidism, and in combination use with fibrates or lipid-modifying doses of niacin (≥1 g/day).
• LIVALO should be administered with caution in patients with impaired renal function, in elderly patients, or when used concomitantly with fibrates or lipid-modifying doses of niacin.
• Concomitant administration of LIVALO with gemfibrozil should be avoided.
• LIVALO therapy should be discontinued if markedly elevated CK levels occur or myopathy is diagnosed or suspected. LIVALO therapy should also be temporarily withheld in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis; hypotension; dehydration; major surgery; trauma; severe metabolic, endocrine, and electrolyte disorders; or uncontrolled seizures).
• Advise patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever, and to discontinue LIVALO if these signs or symptoms appear.
• Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors coadministered with colchicine, and caution should be exercised when prescribing LIVALO with colchicine.
• There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents. IMNM has not been reported with LIVALO therapy.
• Advise patients to promptly report if muscle signs and symptoms persist after discontinuing LIVALO as this may be a sign of IMNM requiring immediate medical attention.

Liver Enzyme Abnormalities

Increases in serum transaminases have been reported with HMG-CoA reductase inhibitors, including LIVALO.

• It is recommended that liver enzyme tests be performed before the initiation of LIVALO and if signs or symptoms of liver injury occur.
• There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including pitavastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with LIVALO, promptly interrupt therapy. If an alternate etiology is not found do not restart LIVALO.
• Advise patients to promptly report any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.
• LIVALO should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of chronic liver disease.

Endocrine Function

Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including LIVALO.

ADVERSE REACTIONS

In short-term controlled studies, the most frequent adverse reactions reported by ≥2% of patients treated with LIVALO 1 mg, 2 mg, and 4 mg, respectively, and at a rate ≥ placebo were back pain (3.9%, 1.8%, 1.4% vs 2.9%), constipation (3.6%, 1.5%, 2.2% vs 1.9%), diarrhea (2.6%, 1.5%, 1.9% vs 1.9%), myalgia (1.9%, 2.8%, 3.1% vs 1.4%), and pain in extremity (2.3%, 0.6%, 0.9% vs 1.9%). This is not a complete listing of all reported adverse events.

For additional information please see the full Prescribing Information provided, or visit www.LivaloRx.com.

© Kowa Pharmaceuticals America, Inc. (2016) - LIV-RA-0101 PI V-11-2016

About Kowa Company, Ltd. and Kowa Pharmaceuticals America, Inc.

Kowa Pharmaceuticals America, Inc., headquartered in Montgomery, AL, is focused primarily in the area of cardiometabolic diseases. Established in September 2008, Kowa Pharmaceuticals America focuses its efforts on the successful commercialization of its current and near-term portfolio of pharmaceutical products, and business development activities. For more information about Kowa Pharmaceuticals America, visit www.kowapharma.com.

LIVALO is a registered trademark of the Kowa group of companies.