Shire to present new data on recombinant human parathyroid hormone and on the management of chronic hypoparathyroidism at the Endocrine Society’s 100th Annual Meeting and Exposition

• Clinical and real-world insights on recombinant human parathyroid hormone (1-84) (rhPTH[1-84]) and the management of chronic hypoparathyroidism to be presented
• Hypoparathyroidism is a rare endocrine disease that can have a significant impact on patients
• New data highlight Shire’s commitment to making a meaningful difference for patients living with this rare disease.

DUBLIN, 13-Mar-2018 — /EuropaWire/ — Shire plc (LSE: SHP, NASDAQ: SHPG), the global biotechnology leader in rare diseases, today announced that it will share new data on recombinant human parathyroid hormone (1-84) (rhPTH[1-84]) and on the management of chronic hypoparathyroidism at the upcoming Endocrine Society’s 100^th Annual Meeting and Exposition (ENDO), on March 17–20 in Chicago, Illinois.

Hypoparathyroidism is a rare endocrine disease that occurs when inadequate levels of parathyroid hormone (PTH) are secreted by the parathyroid glands, resulting in a mineral imbalance in the body expressed by a low concentration of calcium (hypocalcemia) and a high concentration of phosphate (hyperphosphatemia) in the blood.¹ It is estimated that the total number of people with hypoparathyroidism in the United States is about 77,000.² Hypoparathyroidism can have a significant impact on patients through physical and cognitive symptoms.^3,4

“Patients with hypoparathyroidism can experience multiple symptoms and a reduced health-related quality of life,” said Howard Mayer M.D., Senior Vice President and Chief Medical Officer, Shire. “With our continuing program of clinical and real-world insights on the chronic form of this rare endocrine disease, we are committed to expand the understanding of the long-term burden of the disease for patients. At ENDO we will be sharing new data in chronic hypoparathyroidism to help healthcare professionals improve the management of their patients.”

The latest data will reveal clinical and real-world insights into chronic hypoparathyroidism, including effects on renal parameters,⁵ impact on health-related quality-of-life scores,⁶ and an analysis of the latest five-year results from the ongoing RACE study.⁷ These data demonstrate Shire’s long-term commitment to advancing understanding of this rare condition in order to further meet the needs of people living with chronic hypoparathyroidism.

Shire will have two poster presentations and one oral presentation on chronic hypoparathyroidism and will be hosting an exhibit at Booth #4220.

• Comparison of three-year estimated glomerular filtration rates between rhPTH(1-84)-treated patients with chronic hypoparathyroidism and a historical control cohort ⁵ Poster #MON-453 / MON-453
• Symptom burden and HRQoL reported among patients with chronic hypoparathyroidism: impact of treatment with rhPTH (1-84) and with standard therapy ⁶ Poster #MON-452 / MON-452
• Five-year efficacy and safety of rhPTH(1-84) for the treatment of adults with chronic hypoparathyroidism: analysis from the open-label RACE study ⁷ Oral presentation #OR20-3

All abstracts are available on the ENDO website at http://www.abstractsonline.com/pp8/#!/4482.

About Hypoparathyroidism
Chronic hypoparathyroidism is diagnosed in patients with a low concentration of calcium in the blood and inappropriately low PTH levels; for postsurgical hypoparathyroidism, the features of hypoparathyroidism must persist for at least 6 months after surgery to be considered chronic.^3,8

About NATPARA^® (parathyroid hormone) for Injection
NATPARA, available as 25, 50, 75, and 100 mcg per dose strength, is a parathyroid hormone indicated as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism. Because of the potential risk of osteosarcoma, NATPARA is recommended only for patients who cannot be well-controlled on calcium supplements and active forms of vitamin D alone. NATPARA was not studied in patients with hypoparathyroidism caused by calcium-sensing receptor mutations. NATPARA was not studied in patients with acute post-surgical hypoparathyroidism.

Select Important Safety Information
WARNING: POTENTIAL RISK OF OSTEOSARCOMA: In male and female rats, parathyroid hormone caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration. A risk to humans could not be excluded. Because of the potential risk of osteosarcoma, prescribe NATPARA only to patients who cannot be well-controlled on calcium and active forms of vitamin D and for whom the potential benefits are considered to outweigh the potential risk.

Avoid use of NATPARA in patients who are at increased baseline risk for osteosarcoma (including those with Paget’s disease of bone or unexplained elevations of alkaline phosphatase, pediatric and young adult patients with open epiphyses, patients with hereditary disorders predisposing to osteosarcoma or patients with a history of prior external beam or implant radiation therapy involving the skeleton). NATPARA is available only through a restricted program called the NATPARA REMS Program.

NATPARA Warnings and Precautions include: Severe Hypercalcemia — monitor serum calcium when starting or adjusting NATPARA dose and when making changes to coadministered drugs known to raise serum calcium. Severe Hypocalcemia can occur with interruption or discontinuation of NATPARA treatment — Monitor serum calcium and replace calcium and vitamin D. Hypercalcemia increases the risk of digoxin toxicity — in patients using NATPARA concomitantly with digoxin, monitor serum calcium more frequently and increase monitoring when initiating or adjusting NATPARA dose.

The most common adverse reactions associated with NATPARA and occurring in greater than 10% of individuals were: paresthesia, hypocalcemia, headache, hypercalcemia, nausea, hypoaesthesia, diarrhea, vomiting, arthralgia, hypercalciuria and pain in extremity.

For additional safety information, click for the full Prescribing Information:
http://www.shirecontent.com/PI/PDFs/Natpara_USA_ENG.pdf

For further information please contact:

NOTES TO EDITORS

About Shire

Shire is the global leader in serving patients with rare diseases. We strive to develop best-in-class therapies across a core of rare disease areas including hematology, immunology, genetic diseases, neuroscience, and internal medicine with growing therapeutic areas in ophthalmics and oncology. Our diversified capabilities enable us to reach patients in more than 100 countries who are struggling to live their lives to the fullest.

We feel a strong sense of urgency to address unmet medical needs and work tirelessly to improve people’s lives with medicines that have a meaningful impact on patients and all who support them on their journey.

www.shire.com

Forward-Looking Statements

Statements included herein that are not historical facts, including without limitation statements concerning future strategy, plans, objectives, expectations and intentions, projected revenues, the anticipated timing of clinical trials and approvals for, and the commercial potential of, inline or pipeline products, are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire’s results could be materially adversely affected. The risks and uncertainties include, but are not limited to, the following:

• Shire’s products may not be a commercial success;
• increased pricing pressures and limits on patient access as a result of governmental regulations and market developments may affect Shire’s future revenues, financial condition and results of operations;
• Shire depends on third parties to supply certain inputs and services critical to its operations including certain inputs, services and ingredients critical to its manufacturing processes. Any disruption to the supply chain for any of Shire’s products may result in Shire being unable to continue marketing or developing a product or may result in Shire being unable to do so on a commercially viable basis for some period of time;
• the manufacture of Shire’s products is subject to extensive oversight by various regulatory agencies. Regulatory approvals or interventions associated with changes to manufacturing sites, ingredients or manufacturing processes could lead to, among other things, significant delays, an increase in operating costs, lost product sales, an interruption of research activities or the delay of new product launches;
• the nature of producing plasma-based therapies may prevent Shire from timely responding to market forces and effectively managing its production capacity;
• Shire has a portfolio of products in various stages of research and development. The successful development of these products is highly uncertain and requires significant expenditures and time, and there is no guarantee that these products will receive regulatory approval;
• the actions of certain customers could affect Shire’s ability to sell or market products profitably. Fluctuations in buying or distribution patterns by such customers can adversely affect Shire’s revenues, financial conditions or results of operations;
• failure to comply with laws and regulations governing the sales and marketing of its products could materially impact Shire’s revenues and profitability;
• Shire’s products and product candidates face substantial competition in the product markets in which it operates, including competition from generics;
• Shire’s patented products are subject to significant competition from generics;
• adverse outcomes in legal matters, tax audits and other disputes, including Shire’s ability to enforce and defend patents and other intellectual property rights required for its business, could have a material adverse effect on the Shire’s revenues, financial condition or results of operations;
• Shire may fail to obtain, maintain, enforce or defend the intellectual property rights required to conduct its business;
• Shire faces intense competition for highly qualified personnel from other companies and organizations;
• failure to successfully execute or attain strategic objectives from Shire’s acquisitions and growth strategy may adversely affect the Shire’s financial condition and results of operations;
• Shire’s growth strategy depends in part upon its ability to expand its product portfolio through external collaborations, which, if unsuccessful, may adversely affect the development and sale of its products;
• a slowdown of global economic growth, or economic instability of countries in which Shire does business, could have negative consequences for Shire’s business and increase the risk of non-payment by Shire’s customers;
• changes in foreign currency exchange rates and interest rates could have a material adverse effect on Shire’s operating results and liquidity;
• Shire is subject to evolving and complex tax laws, which may result in additional liabilities that may adversely affect the Shire’s financial condition or results of operations;
• if a marketed product fails to work effectively or causes adverse side effects, this could result in damage to Shire’s reputation, the withdrawal of the product and legal action against Shire;
• Shire is dependent on information technology and its systems and infrastructure face certain risks, including from service disruptions, the loss of sensitive or confidential information, cyber-attacks and other security breaches or data leakages that could have a material adverse effect on Shire’s revenues, financial condition or results of operations;
• Shire faces risks relating to the expected exit of the United Kingdom from the European Union;
• Shire incurred substantial additional indebtedness to finance the Baxalta acquisition, which has increased its borrowing costs and may decrease its business flexibility;
• Shire’s ongoing strategic review of its Neuroscience franchise may distract management and employees and may not lead to improved operating performance or financial results; there can be no guarantee that, once completed, Shire’s strategic review will result in any additional strategic changes beyond those that have already been announced; and

a further list and description of risks, uncertainties and other matters can be found in Shire’s most recent Annual Report on Form 10-K and in Shire’s subsequent Quarterly Reports on Form 10-Q, in each case including those risks outlined in “ITEM1A: Risk Factors”, and in Shire’s subsequent reports on Form 8-K and other Securities and Exchange Commission filings, all of which are available on Shire’s website.

All forward-looking statements attributable to us or any person acting on our behalf are expressly qualified in their entirety by this cautionary statement. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof. Except to the extent otherwise required by applicable law, we do not undertake any obligation to update or revise forward-looking statements, whether as a result of new information, future events or otherwise.

References

¹ Shoback D, et al. J Clin Endocrinol Metab. 2016;101(6):2300–12.
² Powers J, et al. J Bone Miner Res. 2013;28(12):2570-6.
³ Bollerslev J, et al. Eur J Endocrinol. 2015;173:G1–G20.
⁴ Hadker N, et al. Endocr Pract. 2014;20(7):671–9.
⁵ Chen K, et al. ENDO, March 2018. Available at: http://www.abstractsonline.com/pp8/#!/4482/presentation/7293
⁶ Chen K, et al. ENDO, March 2018. Available at: http://www.abstractsonline.com/pp8/#!/4482/presentation/7291
⁷ Shoback DM, et al. ENDO, March 2018. Available at: http://www.abstractsonline.com/pp8/#!/4482/presentation/7268
⁸ Brandi ML, et al. J Clin Endocrinol Metab. 2016;101(6):2273–83.

SOURCE: Shire