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Shire Announces Launch Of FOSRENOL(R) In Japan - Management Of Hyperphosphataemia In End-Stage Renal Disease Patients

November 18, 2017

Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, today announces the Japanese launch of FOSRENOL(R) (lanthanum carbonate), which is now available to prescribers and patients in Japan through Shire's strategic alliance partner Bayer Yakuhin Ltd.

FOSRENOL is the first commercially available non-calcium, non-resin phosphate binder in Japan and is used in the control of hyperphosphataemia in chronic renal failure patients on dialysis.

Bayer Yakuhin received an exclusive license from Shire in December 2003 to develop FOSRENOL in Japan, completing Phase II and Phase III clinical trials in the Japanese population.

Studies based on widespread screening programs in Japan indicate the country has an extremely high prevalence of chronic kidney disease (CKD), with an estimated 20 per cent of the total adult population of 103.2 million living with some form of the condition(2). The number of dialysis patients in Japan is estimated at approximately 270,000(3), and is increasing by 10,000 per year(4).

A direct consequence of declining kidney function is the inability to adequately control serum phosphate levels, which leads to hyperphosphataemia5. Elevated phosphate causes disruption in the delicate interplay between the body's levels of calcium, parathyroid hormone and vitamin D. This can lead to bone disorders, impaired bone reservoir function (the bone acts as an important reservoir for phosphate and calcium) and, ultimately, vascular calcification(5). This triad of interrelated abnormalities is known as chronic kidney disease-mineral and bone disorder(6).

Improving bone reservoir function through sustained phosphate control is an important component in preventing vascular calcification(7). Vascular calcification scores help predict mortality in CKD patients(8) and improvements in bone turnover are associated with lower progression of calcification scores(9). Currently, the most commonly prescribed phosphate binder in Japan is calcium carbonate. However, calcium-based phosphate binders have been linked with increased calcium load(10) and the progression of vascular calcification(7).

FOSRENOL delivers sustained phosphate control(11) and over two years in CKD5D patients has been shown to improve bone turnover and volume(12). FOSRENOL is generally well-tolerated, with a predictable tolerability profile observed during the course of treatment for up to six years(11).

"There is a clear medical need in Japan for an effective phosphate binder that provides sustained phosphate control and does not directly contribute to calcium load," said Shirley Wakelin, General Manager FOSRENOL, Shire.

"Shire is proud of its ongoing commitment to renal medicine as it makes FOSRENOL available to an increasing number of patients around the world. Launch in Japan is a key step forward for the brand and represents an important new therapy choice for patients living with ESRD. We are delighted to enter into this new phase of partnership with Bayer, a strongly-established healthcare company with expertise across multiple specialty therapy areas."

With the launch in Japan, FOSRENOL is now available in 33 markets worldwide and further launches are planned throughout 2009.

About Phosphate

Phosphate, which is found in nearly all foods, is absorbed from the gastrointestinal (GI) tract into the blood stream. When the kidneys fail, they do not effectively remove sufficient phosphate, even with the help of blood-cleansing dialysis. While the normal adult range for phosphate is 0.8mmol/L (2.5 mg/dL) to 1.4mmol/L (4.5 mg/dL), the blood phosphate levels of many patients on dialysis can exceed 2.1mmol/L (6.5 mg/dL)(13). Such levels have been linked to a significantly higher complications and risk of death for patients who have undergone at least one year of dialysis14 with over 70 per cent of these patients developing hyperphosphataemia(15).

CKD disrupts the delicate interplay between the body's levels of calcium, parathyroid hormone and vitamin D, leading to hyperphosphataemia and chronic kidney disease-mineral and bone disorder(16). Over time, hyperphosphataemia can ultimately lead to calcification in the heart, lung and some arteries(17). Accumulating evidence shows that hyperphosphataemia contributes to cardiovascular disease(18), which accounts for almost half of all deaths among dialysis patients(19). Studies have shown that cardiovascular mortality in dialysis patients aged 25-34 years is more than five times greater than that in people aged 65-74 in the general population(20).

Since dialysis and diet restrictions alone generally cannot control phosphate levels, patients need to manage hyperphosphataemia by taking phosphate binding agents with food. Such binders "soak up" phosphate in the gastrointestinal tract, before it can be absorbed into the blood.

About FOSRENOL(R) (lanthanum carbonate)

FOSRENOL is indicated as a phosphate binding agent for use in the control of hyperphosphataemia in chronic renal failure patients on haemodialysis or continuous ambulatory peritoneal dialysis1.

FOSRENOL works by binding to dietary phosphate in the GI tract; once bound, the lanthanum/phosphate complex cannot pass through the intestinal lining into the blood stream and is eliminated from the body1. As a consequence, overall phosphate absorption from the diet is decreased significantly.

FOSRENOL is available in a broad range of dosage strengths including 500mg, 750mg, and 1000mg tablets1. Patients taking FOSRENOL can achieve sustained phosphate control with as little as one tablet per meal.

FOSRENOL was first approved in Sweden, in March 2004 and by the US FDA in October 2004. FOSRENOL was subsequently approved in all EU markets by the European Mutual Recognition Procedure and is now launched in 33 markets worldwide. It continues to be approved and made available in new markets around the world.

Important Safety Information

Patients with renal insufficiency may develop hypocalcaemia. Serum calcium levels should therefore be monitored at regular time intervals for this patient population and appropriate supplements given.

No data are available in patients with severe hepatic impairment. Caution should, therefore, be exercised in these patients, as elimination of absorbed lanthanum may be reduced.

FOSRENOL should not be used during pregnancy.

Patients with acute peptic ulcer, ulcerative colitis, Crohn's disease or bowel obstruction were not included in clinical studies with FOSRENOL.

The most commonly reported Adverse Drug Reactions are gastrointestinal reactions such as abdominal pain, constipation, diarrhoea, dyspepsia, flatulence, nausea and vomiting. These are minimized by taking FOSRENOL with food and generally abate with time with continued dosing. Hypocalcaemia was the only other commonly reported adverse reaction. Full prescribing information is available on request.

Shire plc

Shire's strategic goal is to become the leading specialty biopharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on attention deficit hyperactivity disorder, human genetic therapies and gastrointestinal diseases as well as opportunities in other therapeutic areas to the extent they arise through acquisitions. Shire's in-licensing, merger and acquisition efforts are focused on products in specialist markets with strong intellectual property protection and global rights. Shire believes that a carefully selected and balanced portfolio of products with strategically aligned and relatively small-scale sales forces will deliver strong results.

For further information on Shire, please visit the Company's website: shire.

Shire is proud to be an official partner of World Kidney Day (WKD), Thursday 12 March 2009. For further information on WKD visit worldkidneyday

About Bayer Yakuhin Ltd

Bayer Yakuhin Ltd., headquartered in Osaka, is a healthcare company which combines business activities of Bayer Schering Pharma (pharmaceuticals), Consumer Care (OTC product), Diabetes Care (Diabetes care product), and Animal Health (companion and food animal products). Bayer Schering Pharma Division is focused on the following areas: Diagnostic Imaging, Primary Care, Oncology, Speciality care and Women's Healthcare. With innovative products, Bayer Yakuhin aims for leading positions in specialized markets in Japan. Using new ideas, Bayer Yakuhin aims to make a contribution to medical progress and strives to improve the quality of life.

For further information on Bayer Yakuhin Ltd please visit the Company's website: bayer.jp/byl

References

1. Shire plc. FOSRENOL EU summary of product characteristics. Available at emc.medicines. Accessed 03 March 2009

2. Genjiro Kimura. Predicted prevalence in Japan of chronic kidney disease (CKD). Clin Exp Nephrol 2007: 11:188 - 189

3. Yusuke Tsukamoto. End-Stage Renal Disease and its Treatment in Japan; Nephrology Dialysis Transplantation, 2008

4. Enyu Imai et al. Prevalence of chronic kidney disease (CKD) in the Japanese general population predicted by the MDRD equation modified by a Japanese coefficient. Clinical and Experimental Nephrology 2007: 11: 156 - 163

5. Malluche, H.H., H. Mawad and M.C. Monier-Faugere, The Importance of Bone Health in End-Stage Renal Disease: Out of the Frying Pan, Into the Fire? Nephrol Dial Transplant 2004. 19 Suppl 1: pi9-13

6. Danese, et al. Consistent Control of Mineral and Bone Disorder in Incident Haemodialysis Patients. Clin J Am Soc Nephrol, 2008: 3(5) pp1423- 9

7. Block, GA. Prevalence and Clinical Consequences of Elevated Ca x P Product in Hemodialysis Patients. Clin Nephrol 2000; 54(4): 318-324

8. Blacher, J., et al., Arterial Calcifications, Arterial Stiffness and Cardiovascular Risk in End-stage Renal Disease. Hypertension, 2001. 38(4): p. 938-42.

9. Barreto, D.V., et al., Association of Changes in Bone Remodeling and Coronary Calcification in Hemodialysis Patients: A Prospective Study. Am J Kidney Dis, 2008. 52(6): p. 1139-50.

10. Heinrich et al, 2008. Calcium Load During Administration of Calcium Carbonate or Sevelamer in Individuals with Normal Renal Function. Nephrol. Dial Transplant 2008 23 (9): 2861-2867

11. Hutchison, A.J. et al. Long-term Efficacy and Safety Profile of Lanthanum Carbonate: Results for Up to 6 Years of Treatment. Nephron. Clin Practice, 2008. 110(1): pp. c15-23.

12. Malluche, H.H., et al., Improvements in renal osteodystrophy in patients treated with lanthanum carbonate for two years. Clin Nephrol, 2008. 70(4): p. 284-95.

13. E Ritz. The Clinical Management of Hyperphosphatemia. J Nephrol 2005: 18: 221 - 228

14. Block GA et al. Association of Serum Phosphorus and Calcium x Phosphate Product with Mortality Risk in Chronic Hemodialysis Patients: A National Study. Am J Kidney Dis 1998; 31: 607-617

15. Kim J et al. Achievement of Proposed NKF-K/DOQI Bone Metabolism and Disease Guidelines: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). J Am Soc Nephrol 2003; 14: 269A

16. Moe S, et al. Definition, Evaluation, and Classification of Renal Osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006 ;69(11):1945-1953

17. Salusky I.B. and Goodman W.G. Cardiovascular Calcification in End-Stage Renal Disease Nephrol Dial Transplant 2002; 17(2): 336-339

18. Ganesh S.K., et al. Association of Elevated Serum PO(4), Ca x PO(4) Product, and Parathyroid Hormone with Cardiac Mortality Risk in Chronic Hemodialysis Patients. J Am Soc Nephrol 2001;12(10):2131-2138

19. US Renal Data System (USRDS). 2008 ADR/Atlas, Vol 1(5). Available at usrds/2008/pdf/V1_03_2008.pdf. Accessed on 3rd March 2009

20. Foley RN, Parfrey PS, & Sarnak MJ. Clinical Epidemiology of Cardiovascular Disease in Chronic Renal Disease. Am J Kidney Dis 1998; 32 (5 Suppl 3):S112-S119

Shire Plc

View drug information on Fosrenol, lanthanum carbonate.