Hyperparathyroidism - Analysis and Market …Hyperparathyroidism - Analysis and Market Forecasts to 2019 Reference Code: GDHC493PRT Publication Date: October 2012 Hyperparathyroidism:

Hyperparathyroidism - Analysis and Market Forecasts to 2019 GDHC493PRT / Published OCT 2012

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Hyperparathyroidism - Analysis and Market Forecasts to 2019 Reference Code: GDHC493PRT Publication Date: October 2012

Hyperparathyroidism: Key Metrics in Seven Major Pharmaceutical Markets 2011 Epidemiology

Diseased population

Diagnosed population

Prescription population

2011 Market Sales US

EU5

Japan

Total

Pipeline Assessment Number of drugs in Phase I-III

Number of FIC drugs

Key events (2011-2019) Level of Impact

Bundled dialysis payment system in the US in 2011

Hectorol patent expiry in the US in 2014

Sensipar/Mimpara patent expiry in the US and EU5 in 2015

Expected launch of CTAP101 in the US in 2015

Expected launch of KAI-4169 IV in the US in 2016

2019 Market Sales US

EU5

Japan

Total

Source: GlobalData

Hyperparathyroidism Market is forecast to Witness Moderate Growth Until 2019

The hyperparathyroidism therapeutics market is forecast to have moderate growth during the forecast period. GlobalData estimates the global hyperparathyroidism therapeutics market in 2011 was $XX billion, and it is expected to grow at a Compound Annual Growth Rate (CAGR) of XX% to reach $XX billion by 2019.

The key drivers for the market in the forecast period are:

Increase in the hyperparathyroidism patient population, primarily due to increasing Chronic Kidney Disease (CKD) prevalence and an increase in the elderly population

Expected launch of CTAP101 capsules in the US in 2015


Expected launch of KAI-4169 IV in the EU5 (France, Germany, Italy, Spain, and the UK) in 2017

The major barriers for the hyperparathyroidism therapeutics market are:

Inclusion of Zemplar (paricalcitol) and Hectorol (doxercalciferol) in the bundled dialysis payment system in 2011

Patent expiry of Zemplar in 2012

Patent expiry of Hectorol in 2014

Inclusion of Sensipar (cinacalcet) in the US bundled dialysis payment system in 2014

Patent expiry of Sensipar/Mimpara in 2015




1 Table of Contents 1 Table of Contents ............................................................................................................................ 4

1.1 List of Tables ............................................................................................................................. 6 1.2 List of Figures............................................................................................................................ 7

2 Introduction ..................................................................................................................................... 8 2.1 Catalyst ..................................................................................................................................... 8 2.2 Related Reports ........................................................................................................................ 8

3 Disease Overview ............................................................................................................................ 9 3.1 Etiology and Pathophysiology .................................................................................................. 10

3.1.1 Etiology .......................................................................................................................... 10 3.1.2 Pathophysiology ............................................................................................................. 11 3.1.3 Risk Factors ................................................................................................................... 12 3.1.4 Prognosis ....................................................................................................................... 13

3.2 Epidemiology .......................................................................................................................... 13 3.2.1 Prevalence ..................................................................................................................... 13 3.2.2 Diagnosed Prevalence .................................................................................................... 14

3.3 Symptoms ............................................................................................................................... 15 3.4 Diagnosis and Referral ............................................................................................................ 15

3.4.1 Diagnosis ....................................................................................................................... 15 3.4.2 Referral .......................................................................................................................... 16

3.5 Treatment Guidelines .............................................................................................................. 17 3.6 Disease Management .............................................................................................................. 18

3.6.1 Primary Hyperparathyroidism .......................................................................................... 18 3.6.2 Secondary Hyperparathyroidism ..................................................................................... 19 3.6.3 Tertiary Hyperparathyroidism .......................................................................................... 20

4 Competitive Assessment ................................................................................................................ 21 4.1 Overview ................................................................................................................................. 21 4.2 Strategic Competitor Assessment ............................................................................................ 21 4.3 Product Profile - Major Brands ................................................................................................. 23

4.3.1 Sensipar (cinacalcet) ...................................................................................................... 23 4.3.2 Zemplar (paricalcitol) ...................................................................................................... 25 4.3.3 Hectorol (doxercalciferol) ................................................................................................ 27 4.3.4 Oxarol (maxacalcitol) ...................................................................................................... 28

5 Opportunity and Unmet Need ......................................................................................................... 30 5.1 Overview ................................................................................................................................. 30 5.2 Lower Adverse Effect on Serum Calcium and Phosphorus Level ............................................... 31 5.3 New Treatment Options for Primary Hyperparathyroidism ......................................................... 31 5.4 Disease Awareness and Screening Programs in Primary Hyperparathyroidism ......................... 31 5.5 Convenient Dosing Regimen.................................................................................................... 31 5.6 Guidelines for Tertiary Hyperparathyroidism Management ........................................................ 31 5.7 Pricing .................................................................................................................................... 32

6 Pipeline Assessment...................................................................................................................... 33 6.1 Overview ................................................................................................................................. 33 6.2 Strategic Pipeline Assessment ................................................................................................. 33 6.3 Pipeline by Phases of Development ......................................................................................... 33

6.3.1 Phase III Pipeline ............................................................................................................ 33 6.3.2 Phase II Pipeline ............................................................................................................. 34 6.3.3 Phase I Pipeline.............................................................................................................. 34 6.3.4 Preclinical Pipeline.......................................................................................................... 34 6.3.5 Discovery Pipeline .......................................................................................................... 34

6.4 Pipeline by Mechanism of Action .............................................................................................. 35 6.5 Technology Trends Analytic Framework ................................................................................... 36 6.6 Hyperparathyroidism - Promising Drugs in Clinical Development ............................................... 37

6.6.1 CTAP101 ....................................................................................................................... 38 6.6.2 KAI-4169 IV .................................................................................................................... 40

7 Clinical Trials Mapping ................................................................................................................... 42 7.1 Clinical Trials by Country ......................................................................................................... 42 7.2 Clinical Trials by Phase ........................................................................................................... 42 7.3 Clinical Trials by Trial Status .................................................................................................... 43 7.4 Prominent Sponsors ................................................................................................................ 43




8 Current and Future Players ............................................................................................................ 45 8.1 Overview ................................................................................................................................. 45 8.2 Trends in Corporate Strategy ................................................................................................... 45 8.3 Company Profiles .................................................................................................................... 46

8.3.1 Amgen Inc. ..................................................................................................................... 46 8.3.2 Abbott Laboratories ........................................................................................................ 47 8.3.3 Cytochroma Inc. ............................................................................................................. 48 8.3.4 KAI Pharmaceuticals Inc. ................................................................................................ 49 8.3.5 Other Companies in the Hyperparathyroidism Therapeutics Market .................................. 50

9 Licensing and Partnership Deals .................................................................................................... 51 9.1 Overview ................................................................................................................................. 51 9.2 Key Deals and Alliances in the Past 12 Months ........................................................................ 51

10 Market Outlook .............................................................................................................................. 52 10.1 Seven Major Markets Overview................................................................................................ 52 10.2 Regional Analysis .................................................................................................................... 54

10.2.1 US ................................................................................................................................. 54 10.2.2 France............................................................................................................................ 55 10.2.3 Germany ........................................................................................................................ 56 10.2.4 Italy ................................................................................................................................ 56 10.2.5 Spain ............................................................................................................................. 57 10.2.6 UK ................................................................................................................................. 57 10.2.7 Japan ............................................................................................................................. 58

10.3 Key Events .............................................................................................................................. 58 10.4 Drivers and Barriers ................................................................................................................. 59

10.4.1 Drivers for the Hyperparathyroidism Market ..................................................................... 59 10.4.2 Barriers for the Hyperparathyroidism Market .................................................................... 60

11 Appendix ....................................................................................................................................... 61 11.1 Abbreviations .......................................................................................................................... 61 11.2 Bibliography ............................................................................................................................ 62 11.3 Methodology ........................................................................................................................... 64

11.3.1 Coverage ....................................................................................................................... 64 11.3.2 Secondary Research ...................................................................................................... 64 11.3.3 Forecasting Methodology ................................................................................................ 65 11.3.4 Primary Research ........................................................................................................... 67 11.3.5 Expert Panel Validation ................................................................................................... 68

11.4 Physicians and Specialists Included in this Study ..................................................................... 68 11.5 About the Authors .................................................................................................................... 68

11.5.1 Analysts ......................................................................................................................... 68 11.5.2 Global Head of Healthcare Research and Consulting ....................................................... 69

11.6 About GlobalData .................................................................................................................... 69 11.7 Contact Us .............................................................................................................................. 69 11.8 Disclaimer ............................................................................................................................... 69




1.1 List of Tables Table 1: Types of Hyperparathyroidism ............................................................................................. 10 Table 2: Etiology of Primary Hyperparathyroidism ............................................................................. 10 Table 3: Etiology of Secondary Hyperparathyroidism ......................................................................... 11 Table 4: Risk Factors for Hyperparathyroidism .................................................................................. 12 Table 5: Prevalence of Secondary Hyperparathyroidism in Chronic Kidney Disease ........................... 13 Table 6: Total Prevalence of Hyperparathyroidism in the Major Markets, 2011-2019 .......................... 14 Table 7: Diagnosed Prevalence of Hyperparathyroidism in the Major Markets, 2011-2019 .................. 14 Table 8: Symptoms of Hyperparathyroidism ...................................................................................... 15 Table 9: Diagnosis of Hyperparathyroidism ....................................................................................... 16 Table 10: Adoption of Treatment Guidelines by Physicians .................................................................. 17 Table 11: Treatment Guidelines for Hyperparathyroidism .................................................................... 17 Table 12: Surgery Criterion in Primary Hyperparathyroidism ................................................................ 18 Table 13: Monitoring Primary Hyperparathyroidism in Nonsurgical Patients ......................................... 19 Table 14: Leading Treatments for Hyperparathyroidism, 2012 ............................................................. 21 Table 15: Product Profile - Sensipar ................................................................................................... 23 Table 16: Adverse Incidents - Sensipar ............................................................................................... 24 Table 17: Sensipar SWOT Analysis, 2012........................................................................................... 25 Table 18: Product Profile - Zemplar .................................................................................................... 25 Table 19: Zemplar SWOT Analysis, 2012 ........................................................................................... 26 Table 20: Product Profile - Hectorol .................................................................................................... 27 Table 21: Hectorol SWOT Analysis, 2012 ........................................................................................... 28 Table 22: Product Profile - Oxarol ....................................................................................................... 28 Table 23: Oxarol SWOT Analysis, 2012 .............................................................................................. 29 Table 24: Overall Unmet Needs - Current Level of Attainment ............................................................. 30 Table 25: Hyperparathyroidism - Phase III Pipeline, 2012 .................................................................... 33 Table 26: Hyperparathyroidism - Phase II Pipeline, 2012 ..................................................................... 34 Table 27: Hyperparathyroidism - Phase I Pipeline, 2012 ...................................................................... 34 Table 28: Hyperparathyroidism - Preclinical Pipeline, 2012 .................................................................. 34 Table 29: Hyperparathyroidism - Discovery Pipeline, 2012 .................................................................. 34 Table 30: Comparison of Mechanisms of Actions in Development for Hyperparathyroidism, 2012 ......... 36 Table 31: Hyperparathyroidism - Promising Drugs in Clinical Development .......................................... 37 Table 32: Product Profile - CTAP101 .................................................................................................. 38 Table 33: CTAP101 SWOT Analysis, 2012 ......................................................................................... 39 Table 34: Product Profile - KAI-4169 IV............................................................................................... 40 Table 35: KAI-4169 IV SWOT Analysis, 2012 ...................................................................................... 41 Table 36: Hyperparathyroidism Therapeutics, Clinical Trials by Phase, 2012 ....................................... 42 Table 37: Hyperparathyroidism Therapeutics, Clinical Trials by Status, 2012 ....................................... 43 Table 38: Hyperparathyroidism - Overall Sponsor Mix, 2012 ................................................................ 43 Table 39: Key Companies in the Hyperparathyroidism Market, 2012 .................................................... 45 Table 40: Amgen’s Hyperparathyroidism Therapy Portfolio Assessment, 2012 ..................................... 46 Table 41: Amgen’s Hyperparathyroidism Therapy Portfolio SWOT Analysis, 2012 ............................... 46 Table 42: Abbott’s Hyperparathyroidism Therapy Portfolio Assessment, 2012 ...................................... 47 Table 43: Abbott’s Hyperparathyroidism Therapy Portfolio SWOT Analysis, 2012 ................................ 47 Table 44: Cytochroma’s Hyperparathyroidism Therapy Portfolio Assessment, 2012 ............................. 48 Table 45: Cytochroma’s Hyperparathyroidism Therapy Portfolio SWOT Analysis, 2012 ........................ 48 Table 46: KAI Pharmaceutical’s Hyperparathyroidism Therapy Portfolio Assessment, 2012 .................. 49 Table 47: KAI Pharmaceutical’s Hyperparathyroidism Therapy Portfolio SWOT Analysis, 2012 ............ 49 Table 48: Portfolio Assessment - Other Leading Players in Hyperparathyroidism Market, 2012 ............ 50 Table 49: Strategic Deals and Alliances for Hyperparathyroidism, 2012 ............................................... 51 Table 50: Sales Forecasts for Hyperparathyroidism in the Seven Major Markets, 2011-2019 ................ 53 Table 51: Sales Forecasts for Hyperparathyroidism in the US, 2011-2019 ........................................... 55 Table 52: Sales Forecasts for Hyperparathyroidism in France, 2011-2019 ........................................... 55 Table 53: Sales Forecasts for Hyperparathyroidism in Germany, 2011-2019 ........................................ 56 Table 54: Sales Forecasts for Hyperparathyroidism in Italy, 2011-2019................................................ 56 Table 55: Sales Forecasts for Hyperparathyroidism in Spain, 2011-2019 ............................................. 57 Table 56: Sales Forecasts for Hyperparathyroidism in the UK, 2011-2019 ........................................... 57 Table 57: Sales Forecasts for Hyperparathyroidism in Japan, 2011-2019 ............................................ 58 Table 58: Key Events Impacting Sales for Hyperparathyroidism, 2012 ................................................. 58 Table 59: Hyperparathyroidism Market - Drivers and Barriers, 2012 ..................................................... 59 Table 60: Key Launch Dates .............................................................................................................. 65 Table 61: Key Patent Expiries............................................................................................................. 66




1.2 List of Figures Figure 1: Parathyroid Glands ............................................................................................................... 9 Figure 2: Pathophysiology of Secondary Hyperparathyroidism ............................................................ 12 Figure 3: Referral and Management of Secondary Hyperparathyroidism in CKD Patients .................... 16 Figure 4: Strategic Competitor Assessment of Marketed Products in Hyperparathyroidism, 2012 ......... 22 Figure 5: Opportunity and Clinical Unmet Need in Hyperparathyroidism, 2012..................................... 30 Figure 6: Hyperparathyroidism Therapeutics Pipeline by Phase of Clinical Development, 2012 ............ 33 Figure 7: Hyperparathyroidism - Pipeline by Mechanism of Action, 2012 ............................................. 35 Figure 8: Technology Trends Analytic Framework for Hyperparathyroidism Pipeline, 2012 .................. 36 Figure 9: Technology Trends Analytic Framework - Unmet Need Gap Analysis, 2012.......................... 37 Figure 10: Hyperparathyroidism Therapeutics, Clinical Trials by Country, 2012 ..................................... 42 Figure 11: Hyperparathyroidism - Leading Companies Participating in Clinical Trials, 2012.................... 44 Figure 12: Sales Forecasts for Hyperparathyroidism in the Seven Major Markets, 2011-2019 ................ 53 Figure 13: Seven Major Market Sales for Hyperparathyroidism by Region, 2011-2019 .......................... 54




2 Introduction

2.1 Catalyst This report explores the current and future hyperparathyroidism market in the context of the upcoming patent expirations of Zemplar, Hectorol and Sensipar/Mimpara, which will change the competitive landscape in the foreseeable future. Additionally, this report examines the effects of the new bundled dialysis payment system in the US; the payment system is expected to alter the dynamics of this market for patients and payers alike thanks to the reimbursement caps it includes. Lastly, GlobalData projects the impact of the imminent launches of CTAP101 and KAI-4169 IV.

2.2 Related Reports GlobalData (2012). End-stage Renal Disease Therapeutics - Pipeline Assessment and Market Forecasts to 2019. June 2012, GDHC480PRT.




6.4 Pipeline by Mechanism of Action In the current hyperparathyroidism therapeutics pipeline, pharmaceutical companies are focusing on developing drugs with novel mechanisms of action for improved efficacy and safety; out of XX molecules in the pipeline, XX are FIC molecules.

The hyperparathyroidism pipeline consists of XX vitamin D receptor agonists, XX vitamin D pro-hormone, XX molecule with a dual mechanism of action (CYP24 inhibition coupled with vitamin D receptor agonist), XX CaSR agonist with XX different formulations, and XX molecule with an unknown mechanism of action.

Current therapies for hyperparathyroidism have blood calcium, phosphorus and iPTH-related adverse effects but according to Phase II clinical trials results, the vitamin D pro-hormone (CTAP101) has no such adverse effects, which has the potential to influence current treatment patterns. KAI Pharmaceuticals is using an innovative approach to deliver KAI-4169, a CaSR agonist, in a once-daily transdermal drug delivery system. Currently KAI-4169 transdermal is in the preclinical stage, while KAI-4169 IV is in Phase IIb of clinical development.

Figure 7: Hyperparathyroidism - Pipeline by Mechanism of Action, 2012

Vitamin-D receptor agonist

Vitamin-D receptor agonist & CYP24 enzyme inhibitor

Vitamin-D pro-hormone

CaSR agonist

NA

Source: GlobalData, Pharma eTrack, [Accessed on October 1, 2012]




10 Market Outlook The key products in the hyperparathyroidism therapeutics market are Sensipar, Zemplar, Hectorol and Oxarol. Other generic drugs available in the market include calcitriol, alfacalcidol and ergocalciferol. During the forecast period, the patents of three of the major products are going to expire and two new drugs are expected to launch.

10.1 Seven Major Markets Overview GlobalData has estimated the global hyperparathyroidism therapeutics market to be valued at $XX billion in 2011. It is expected to grow at a Compound Annual Growth Rate (CAGR) of XX% over the next eight years to reach $XX billion by 2019. This moderate growth can be attributed to a number of events and a growing patient population. The major events that will affect the hyperparathyroidism therapeutics market during the forecast period are:

Inclusion of Zemplar and Hectorol in the bundled dialysis payment system in 2011

Patent expiry of Zemplar in 2012

Patent expiry of Hectorol in 2014

Inclusion of Sensipar in the bundled dialysis payment system in 2014

Patent expiry of Sensipar/Mimpara in 2015

Expected launch of CTAP101 capsules in 2015


Expected launch of KAI-4169 IV in EU5 in 2017

The market in the US accounted for the highest percentage of global revenues (XX%), followed by Japan, Germany and Italy. The five main EU countries contributed XX% and Japan contributed XX% of global revenues in 2011. The US market is expected to dominate the global market during the forecast period with a moderate CAGR of XX%. Japan is expected to reach XX% global market share with a CAGR of XX%, largely because no drug patents are due to expire in Japan during the forecast period.

Sensipar/Mimpara, a calcimimetic drug, is the leading product in the hyperparathyroidism market with global annual sales of more than $XXm. It is also the only approved drug for PHPT. Sensipar will be included in the bundled dialysis payment in 2014 in the US and its patent is also going to expire in 2015; both of these events will reduce Sensipar’s market share. In Japan’s hyperparathyroidism market, Oxarol is the major product, with above $XXm sales in 2011.




Figure 12: Sales Forecasts for Hyperparathyroidism in the Seven Major Markets, 2011-2019

2011 2012 2013 2014 2015 2016 2017 2018 2019

Rev

enue

($m

)

CAGR (2011–2019): XX%

Source: GlobalData; USRDS, 2011; Horio et al., 2010; Joy et al., 2007; CDC, 2007; Zhang and Rothenbacher, 2008; Wermers et al., 2006; Melton, 2002; Levin et al., 2007

Table 50: Sales Forecasts for Hyperparathyroidism in the Seven Major Markets, 2011-2019

Year 2011 2012 2013 2014 2015 2016 2017 2018 2019 CAGR (2011-2019) (%)

Total Sales ($m)

Growth Rate (%)

Source: GlobalData; USRDS, 2011; Horio et al., 2010; Joy et al., 2007; CDC, 2007; Zhang and Rothenbacher, 2008; Wermers et al., 2006; Melton, 2002; Levin et al., 2007




11 Appendix

11.1 Abbreviations AACE : American Association of Clinical Endocrinologists

AAES : American Association of Endocrine Surgeons

CAGR : Compound Annual Growth Rate

CaSR : Calcium-Sensing Receptor

CKD : Chronic Kidney Disease

CKD-MBD : Chronic Kidney Disease Related Mineral and Bone Disorder

eGFR : estimated Glomerular Filtration Rate

EMA : European Medicines Agency

ESRD : End Stage Renal Disease

EU5 : France, Germany, Italy, Spain and the UK

FDA : Food and Drug Administration

FHH : Familial Hypocalciuric Hypercalcemia

FIC : First-in-Class

FIHPT : Familial Isolated Hyperparathyroidism

G7 : France, Germany, Italy, Japan, Spain, the UK and the US

GERD : Gastroesophageal Reflux Disease

GFR : Glomerular Filtration Rate

HPT-JT : Hyperparathyroid-Jaw Tumor Syndrome

iPTH : intact Parathyroid Hormone

IV : Intravenous

JP : Japan

MEN : Multiple Endocrine Neoplasia Syndromes

MTPC : Mitsubishi Tanabe Pharma Corporation

NIH : National Institutes of Health

PHPT : Primary Hyperparathyroidism

PKC : Protein Kinase C

PTH : Parathyroid Hormone

SHPT : Secondary Hyperparathyroidism

SWOT : Strengths Weaknesses Opportunities and Threats

THPT : Tertiary Hyperparathyroidism




11.2 Bibliography Abbott Laboratories, Paricalcitol Compared to Maxacalcitol in Chronic Kidney Disease Patients With

Secondary Hyperparathyroidism, NCT00990704, http://clinicaltrials.gov/ct2/show/NCT00990704. [Accessed October 1, 2012].

Abbott Laboratories (2011). About Secondary Hyperparathyroidism (SHPT). Available from: www.zemplar.com/secondary-hyperparathyroidism.aspx. [Accessed June 27, 2012].

Adami S, et al. (2002). Epidemiology of primary hyperparathyroidism in Europe. Journal of Bone and Mineral Research; 17(2): N18-23.

Ayuk J and Gittoes N (2012). Primary hyperparathyroidism: Aetiology. BMJ Publishing Group Limited. Available from: http://bestpractice.bmj.com/best-practice/monograph/133/basics/aetiology.html. [Accessed September 7, 2012].

Bilezikian JP, et al. (2009). Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Third International Workshop. The Journal of Clinical Endocrinology and Metabolism; 94(2): 335-339.

CDC (2007). Prevalence of Chronic Kidney Disease and Associated Risk Factors. Morbidity and Mortality Weekly Report; 56(08): 161-165.

CDC (2009). An Estimated 26 Million Adults in the United States have Chronic Kidney Disease (CKD). Available from: www.cdc.gov/Features/dsChronicKidneyDisease/index.html. [Accessed September 7, 2012].

Cytochroma Inc. (2012a). Cytochroma Announces Positive Phase 2b Results for CTAP101 Capsules at National Kidney Foundation Meeting. Available from: www.cytochroma.com/news/phase_2b_results.html. [Accessed June 5, 2012].

Cytochroma Inc. (2012b). Lead Candidates. Available from: www.cytochroma.com/pipeline/programs.html. [Accessed October 1, 2012].

Cytochroma Inc., Safety and Efficacy Study of CTAP101 in Chronic Kidney Disease Subjects With Vitamin D Insufficiency and Secondary Hyperparathyroidism (SHPT), NCT01219855, http://clinicaltrials.gov/show/NCT01219855. [Accessed October 1, 2012].

Eastell R, et al. (2009). Diagnosis of Asymptomatic Primary Hyperparathyroidism: Proceedings of the Third International Workshop. The Journal of Clinical Endocrinology and Metabolism; 94(2): 340-350.

Healthinaging (2012). Kidney Problems: Basic Facts & Information. Available from: www.healthinaging.org/aging-and-health-a-to-z/topic:kidney-problems. [Accessed September 7, 2012].

Hectorol (2011). Interactive prescribing information. Available from: www.accessdata.fda.gov/drugsatfda_docs/label/2011/020862s030lbl.pdf.

Horio M, et al. (2010). Modification of the CKD epidemiology collaboration (CKD-EPI) equation for Japanese: accuracy and use for population estimates. American Journal of Kidney Diseases; 56(1): 32-38.

Hybrigenics (2012). Hyperparathyroidism. Available from: www.hybrigenics.com/Pharma/Pharma-Content/Hyperparathyroidism.html. [Accessed October 1, 2012].

Joy MS, et al. (2007). Outcomes of Secondary Hyperparathyroidism in Chronic Kidney Disease and the Direct Costs of Treatment. Journal of Managed Care Pharmacy; 13(5): 397-411.

KAI Pharmaceuticals, Open-label Study to Assess the Long-term Safety and Efficacy of KAI-4169 in Patients With Secondary Hyperparathyroidism, NCT01576146, http://clinicaltrials.gov/show/NCT01576146. [Accessed October 1, 2012].

KAI Pharmaceuticals, Safety, Tolerability and Efficacy of KAI-4169 in Hemodialysis Subjects With Secondary Hyperparathyroidism, NCT01254565, http://clinicaltrials.gov/show/NCT01254565. [Accessed October 1, 2012].

Kasiske BL, et al. (2003). K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. American Journal of Kidney Diseases; 42(4): S34.




Langdahl BL and Ralston SH (2012). Diagnosis and management of primary hyperparathyroidism in Europe. Q J Med; 105: 519-525.

Lawrence K, et al. (2011). Hyperparathyroidism. Medscape. Available from: http://emedicine.medscape.com/article/127351-overview. [Accessed June 20, 2012].

LEO Pharma A/S (2012). Pipeline. Available from: www.leo-pharma.com/Home/Research-and-Development/Pipeline.aspx. [Accessed October 1, 2012].

Levin A, et al. (2007). Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: Results of the study to evaluate early kidney disease. Kidney International; 71: 31-38.

Melton LJ (2002). The epidemiology of primary hyperparathyroidism in North America. Journal of Bone and Mineral Research; 17(2): N12-7.

National Kidney Foundation (2003). KDOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Available from: www.kidney.org/professionals/kdoqi/guidelines_bone/guide16.htm. [Accessed September 7, 2012].

Nolan CR (2005). Phosphate binder therapy for attainment of K/DOQI bone metabolism guidelines. Kidney International; 68(96): S7-S14.

Norman Parathyroid Center (2012a). Hyperparathyroidism Diagnosis: Diagnosing Parathyroid Disease. Available from: www.parathyroid.com/diagnosis.htm. [Accessed September 7, 2012].

Norman Parathyroid Center (2012b). Parathyroid Tumors: What Causes Parathyroid Adenomas. Available from: www.parathyroid.com/causes.htm. [Accessed June 20, 2012].

Norman Parathyroid Center (2012c). Symptoms of Hyperparathyroidism. Available from: www.parathyroid.com/parathyroid-symptoms.htm. [Accessed June 20, 2012].

Otero A, et al. (2005). Epidemiology of chronic renal disease in the Galician population: Results of the pilot Spanish EPIRCE study. Kidney International; 68(99): S16-S19.

Parathyroid Cancer Guide (2012). Available from: www.drugs.com/health-guide/parathyroid-cancer.html. [Accessed June 20, 2012].

Saliba W and El-Haddad B (2009). Secondary Hyperparathyroidism: Pathophysiology and Treatment. The Journal of the American Board of Family Medicine; 22(5): 574-581.

Schlosser K, et al. (2004). Medical and Surgical Treatment for Secondary and Tertiary Hyperparathyroidism. Scandinavian Journal of Surgery; 93: 288-297.

Sensipar (2011). Interactive prescribing information. Available from: www.accessdata.fda.gov/drugsatfda_docs/label/2011/021688s017lbl.pdf.

Silverberg SJ, et al. (1999). A 10-Year Prospective Study of Primary Hyperparathyroidism With or Without Parathyroid Surgery. The New England Journal of Medicine; 341(17): 1249-1255.

Sonora Quest Laboratories (2012). Testing and Management of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease. Available from: www.sonoraquest.com/uploads/docs/CKD_Treatment_Algorithm_SQL.pdf.

Stack BC (2011a). Secondary Hyperparathyroidism: Prognosis. BMJ Publishing Group Limited. Available from: http://bestpractice.bmj.com/best-practice/monograph/1107/follow-up/prognosis.html. [Accessed September 7, 2012].

Stack BC (2011b). Secondary Hyperparathyroidism: Treatment guidelines. BMJ Publishing Group Limited. Available from: http://bestpractice.bmj.com/best-practice/monograph/1107/treatment/guidelines.html. [Accessed September 7, 2012].

Stevens PE, et al. (2007). Chronic kidney disease management in the United Kingdom: NEOERICA project results. Kidney International; 72: 92-99.

The Cleveland Clinic (2000). Primary Hyperparathyroidism. Available from: http://my.clevelandclinic.org/disorders/primary_hyperparathyroidism/rheumatology_overview.aspx. [Accessed June 27, 2012].




United States Census Bureau (2012). International Data Base. Available from: www.census.gov/population/international/data/idb/informationGateway.php. [Accessed September 7, 2012].

United States Renal Data System (2011). Annual Data Report. Available from: www.usrds.org/adr.aspx. [Accessed June 27, 2012].

Wermers RA, et al. (2006). Incidence of Primary Hyperparathyroidism in Rochester, Minnesota, 1993-2001: An Update on the Changing Epidemiology of the Disease. Journal of Bone and Mineral Research; 21: 171-177.

Zhang QL and Rothenbacher D (2008). Prevalence of chronic kidney disease in population-based studies: Systematic review. BMC Public Health; 8:117.

Zemplar (2011). Interactive prescribing information. Available from: www.accessdata.fda.gov/drugsatfda_docs/label/2011/021606s009lbl.pdf.

11.3 Methodology GlobalData’s dedicated research and analysis teams consist of experienced professionals with pedigrees in marketing and market research, consulting backgrounds in the pharmaceutical industry, and advanced statistical expertise.

GlobalData adheres to the Codes of Practice of the Market Research Society (www.mrs.org.uk) and the Strategic and Competitive Intelligence Professionals (www.scip.org).

All GlobalData databases are continuously updated and revised. The following research methodology is followed for all databases and reports.

11.3.1 Coverage GlobalData’s coverage is designed to ensure that it represents the most up-to-date vision of the industry possible.

Changes to industry taxonomy are based on extensive research of companies, associations and competitors.

Company coverage is based on three key factors: Revenues, products and media attention/innovation/ market potential.

The estimated revenues of all major companies, including private and governmental, are gathered and used to prioritize coverage; and

Companies which are making the news, or which are of particular interest due to their innovative approach are prioritized.

GlobalData aims to provide coverage on all major news events and deals in the pharmaceutical industry, updated on a daily basis.

The coverage is further streamlined and strengthened with additional input from GlobalData’s panel of experts (see below).

11.3.2 Secondary Research The research process begins with exhaustive secondary research into internal and external sources to gather qualitative and quantitative information relating to each market.

The secondary research sources that are typically referred to include, but are not limited to:

Company websites, annual reports, financial reports, broker reports, investor presentations and SEC Filings;

Industry trade journals, scientific journals and other technical literature;

Internal and external proprietary databases,

Relevant patent and regulatory databases,

National government documents, statistical databases and market reports,




Procedure registries, and

News articles, press releases and web-casts relating to companies operating in the market.

11.3.3 Forecasting Methodology GlobalData uses a patient-based forecast to determine the market size for therapeutic indications. Estimates for the 2019 market for hyperparathyroidism in the seven major pharmaceutical markets (US, France, Germany, Italy, Spain, UK, and Japan) are based on a number of sources, including Key Opinion Leader (KOL) interviews, prescriber surveys, company reports, press releases, published articles, proprietary databases and general news media.

For hyperparathyroidism, total patient share exceeds 100% when patients are prescribed more than one drug. The estimated number of compliant days for each drug is determined from prescriber surveys, KOL interviews and internal estimated compliance rates based on the drug’s profile.

GlobalData’s proprietary forecast model does not account for inflation and is in 2011 dollars. The following paragraphs outline the underlying assumptions for the forecast.

11.3.3.1 Diagnosed Hyperparathyroidism Patients

Hyperparathyroidism patients are segmented into primary, secondary and tertiary in each major market. Total hyperparathyroidism population includes undiagnosed and diagnosed patients in these segments. GlobalData multiplied the total hyperparathyroidism population in each segment by a diagnosis rate obtained from primary research interviews with key opinion leaders in the G7 countries to determine the diagnosed patient population in each hyperparathyroidism segment. Diagnosis rates of primary, secondary and tertiary hyperparathyroidism are expected to rise during the forecast period primarily due to increasing patient awareness, government screening programs and availability of better diagnostic tests.

11.3.3.2 Percent Drug-treated Patients

Percent drug-treated patients are calculated as a percentage of the diagnosed population. This treated population is calculated using research publications and interviews with physicians in the G7 countries and is used to estimate the patient volumes for the hyperparathyroidism disease under consideration. The percent drug-treated patients for SHPT and THPT are expected to increase during the forecast period due to the introduction of products with improved safety profile and ease of administration. The percent drug-treated patients for PHPT are decreasing. Parathyroidectomy is the treatment of choice in PHPT and there is growing unanimity that surgery may eventually be appropriate in the majority of PHPT patients (Bilezikian et al., 2009; Langdahl and Ralston, 2012).

11.3.3.3 Drugs Included in Each Therapeutic Class

Vitamin D analogs include Zemplar (paricalcitol), Hectorol (doxercalciferol), Oxarol (maxacalcitol), calcitriol, alfacalcidol, ergocalciferol

Calcium sensing receptor agonists include Sensipar/Mimpara/Regpara and KAI-4169 IV

Vitamin D pro-hormones include CTAP101

11.3.3.4 Launch and Patent Expiry Dates

Table 60: Key Launch Dates

Product US EU5 Japan

Zemplar (paricalcitol) 1998 1998 NA

Hectorol (doxercalciferol) 1999 NA NA

Sensipar (cinacalcet) 2004 2004 2007

Oxarol (maxacalcitol) NA NA 2000

CTAP101 (calcifediol) 2015 NA NA

KAI-4169 IV 2016 2017 NA

Source: GlobalData




Table 61: Key Patent Expiries Product US EU5 Japan

Zemplar (paricalcitol) 2012 2012 NA

Hectorol (doxercalciferol) 2014 NA NA

Sensipar (cinacalcet) 2015 2015 NA

Source: GlobalData

11.3.3.5 General Pricing Assumptions

We calculate the price per day of each drug based on the most frequently prescribed formulations, as identified from our KOL interviews, prescribing surveys, and other data sources. All prices are based on ex-manufacturer prices.

US prices are obtained from Thomson Reuters’ Red Book.

For European and Japanese pricing, we use country-specific drug pricing publications and apply discount rates to back-calculate ex-manufacturer pricing. To determine the right discount for each country, we utilize surveys published by the European Federation of Pharmaceutical Industries and Associations (EFPIA) and discount rates published by IMS Health.

For Japanese pricing, we used SSRI’s Yakka (National Health Insurance) drug price database. During our forecast, the following price cuts are applied every two years (on even-numbered years to account for the Japanese government (Ministry of Health, Labor, and Welfare) mandated biennial price cuts. The most recent price cuts occurred in April 2012.

2% for newer drugs (marketed in Japan for less than two years) and drugs with no marketed competitor in the same class.

6% for long-listed drugs (drugs that have expired patents and generics are available). Calcitriol and alfacalcidol fall in this category.

4% for all other drugs. Oxarol (maxacalcitol) and Regpara (cinacalcet) fall in this category.

11.3.3.6 Individual Drug Assumptions

Sensipar/Mimpara/Regpara (cinacalcet) assumptions:

Clinical positioning: Sensipar is the only approved calcimimetic drug for the treatment of SHPT in hemodialysis patients and PHPT patients who are unable to undergo parathyroidectomy. Sensipar is also indicated for the treatment of parathyroid carcinoma.

Treatment days: The prescribed number of treatment days for Sensipar is 365 days based on a once-daily dosing.

Average cost of therapy: The average annual cost of therapy for Sensipar is $5,965.19 across the 7MM based on 30mg, 60mg and 90mg pill sizes (estimated daily dose of 30-90mg once daily). No generics are available.

Compliance: We assume a compliance rate of 60-70%, which takes into account missed doses owing to the chronic administration of this agent.

Zemplar (paricalcitol) assumptions:

Clinical positioning: Zemplar is used in the treatment of SHPT associated with CKD stages 3 and 4 and in patients on hemodialysis or peritoneal dialysis.

Treatment days: The prescribed number of treatment days for Zemplar is 365 days based on a once-daily dosing and 180 days based on three times a week dosing.

Average cost of therapy: The average annual cost of therapy for Zemplar is $2,710.46 across the 7MM based on 1µg, 2µg, 4µg capsule and 5µg vial (estimated daily dose of 1-4µg daily). No generics are available.





Hectorol (doxercalciferol) assumptions:

Clinical positioning: Hectorol is one of the preferred choices to treat SHPT in both hemodialysis and pre-dialysis SHPT patients.

Treatment days: The prescribed number of treatment days for Hectorol is 365 days based on a once-daily dosing and 180 days based on three times a week dosing.

Average cost of therapy: The average annual cost of therapy for Hectorol is $3,026.70 in the US based on 2µg, 4µg vial for dialysis patients and 1µg, 2.5µg capsule for both pre-dialysis and dialysis patients (estimated daily dose of 1-4µg daily). No generics are available.


Oxarol (maxacalcitol) assumptions:

Clinical positioning: Oxarol is used in hemodialysis patients in CKD stage 5 patients and is the only approved vitamin D analog for SHPT in Japan.

Treatment days: The prescribed number of treatment days for Oxarol is 180 days based on three times a week dosing.

Average cost of therapy: The average annual cost of therapy for Oxarol is $3,037.44 in Japan. The cost of 2.5µg, 5µg and 10µg injection in Japan is $15.96, $20.63 and $30.40 respectively. No generics are available.


11.3.3.7 Generic Erosion

The prices of drugs with expiring patents are decreased during our forecast to account for generic competition. The percentage of branded prescriptions shifting to generics is adjusted to reflect the overall strength of the generic drug market in each country.

11.3.3.8 Pricing of Pipeline Agents

The annual cost of CTAP101 (30µg) is likely to be priced similarly to the 2011 base year cost of Zemplar (1µg) given its once-daily oral formulation and good safety and efficacy.

The annual cost of KAI-4169 IV (10mg) is likely to be priced similarly to the 2011 base year cost of Sensipar (30mg) due to its good safety and efficacy in Phase IIa clinical trial results.

11.3.4 Primary Research GlobalData conducts hundreds of primary interviews a year with industry participants and commentators in order to validate its data and analysis. A typical research interview fulfills the following functions:

Provides first-hand information on factors such as market size, market trends, growth trends, competitive landscape and future outlook;

Helps in validating and strengthening the secondary research findings; and

Further develops the analysis team’s expertise and market understanding.

Primary research involves e-mail interactions, telephonic interviews as well as face-to-face interviews for each market, category, segment and sub-segment across different geographies.

The participants who typically take part in interviews include, but are not limited to:

Industry participants: CEOs, VPs, marketing/product managers, market intelligence managers and national sales managers;

Hospital stores, laboratories, pharmacies, distributors and paramedics;

Outside experts: Investment bankers, valuation experts, research analysts specializing in specific pharmaceutical markets; and




Key opinion leaders: Physicians and surgeons specializing in different therapeutic areas corresponding to different kinds of pharmaceuticals.

11.3.5 Expert Panel Validation GlobalData uses a panel of experts to cross-verify its databases and forecasts.

GlobalData’s expert panel comprises marketing managers, product specialists, international sales managers from pharmaceutical companies, academics from research universities, KOLs from hospitals, consultants from venture capital funds, and distributors/suppliers of pharmaceuticals and related supplies. Historic data and forecasts undergo scrutiny from GlobalData’s expert panel and are adjusted in accordance with their feedback.

11.4 Physicians and Specialists Included in this Study Mario Gennaro Cozzolino, M.D., Ph.D.

Professor of Nephrology, University of Milan, Milan, Italy

Hartmut Horst Malluche, M.D., FACP

Professor and Chief, Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Lexington, Kentucky

Moustafa Moustafa, M.D.

Nephrologist, South Carolina Nephrology and Hypertension Center, Orangeburg, South Carolina

Juan M. Rodriguez Portillo, M.D.

Nephrology Service, Research Unit, Hospital Reina Sofia, University of Cordoba, Cordoba, Spain

11.5 About the Authors 11.5.1 Analysts Neeraj Singh Sisoudia, M.Pharm. is an analyst in GlobalData’s Therapeutics Analysis Team. Prior to this role, he was an Assistant Professor at Vivek College of Technical Education (India). Mr. Neeraj Sisoudia has over six years’ experience in academics and market research and has published several research papers in national and international journals. He has a Master’s degree in Drug Regulatory Affairs from Maharshi Dayanand University (India) and has worked on regulatory aspects of biotechnological products.

Claire Herman, MPH is GlobalData’s Head of Cardiovascular, Metabolic, and Infectious Disease. She has more than 10 years of experience in the healthcare industry, during which she has evaluated disease markets across therapeutic areas. Claire began her career at Decision Resources, where she worked as an Analyst and Epidemiologist evaluating the potential of pipeline drugs in the context of current medical practice and developing patient-based market forecasts. Prior to her current role, Claire was the Director of Autoimmune/Inflammation, CNS, and Ophthalmology for Citeline/Informa’s Trialtrove database, where she managed her team’s daily operations and was involved in various product enhancement initiatives. Previously, she was a Manager in Citeline’s consulting division, where she developed customized analyses of the clinical trials competitive landscape. Claire holds a Bachelor’s degree from Wellesley College and a Master of Public Health degree in epidemiology from Boston University.




11.5.2 Global Head of Healthcare Research and Consulting Bonnie Bain, Ph.D. is Global Head of Healthcare Research & Consulting for GlobalData, managing the Medical and Pharmaceutical arms of the business. Prior to this role, she was Vice President and Global Research & Analysis Director for Informa where she oversaw the global strategy and operations for Datamonitor Healthcare’s syndicated business. Dr. Bain has over 15 years’ experience in the healthcare sector and a proven track record of developing innovative solutions on both the client and vendor sides of the business. Prior to joining Informa, Bonnie was Director of Product Development at Wood Mackenzie where she oversaw development and management of two product lines. Bonnie also worked for several years at Decision Resources as an Analyst and Project. On the client side of the industry, Bonnie worked for several years as a Senior Manager in Marketing Strategy and Analytics at Boston Scientific where her work contributed to the successful commercialization of the first ever Access and Visualization Platform at the company. She has a PhD in Biochemistry and Molecular Biology from Purdue University and was a Post-Doctoral Fellow in Molecular Pharmacology at The University of Miami School of Medicine.

11.6 About GlobalData GlobalData is a leading global provider of business intelligence in the Healthcare industry. GlobalData provides its clients with up-to-date information and analysis on the latest developments in drug research, disease analysis, and clinical research and development. Our integrated business intelligence solutions include a range of interactive online databases, analytical tools, reports and forecasts. Our analysis is supported by a 24/7 client support and analyst team. GlobalData has offices in New York, Boston, London, India and Singapore.

11.8 Disclaimer All Rights Reserved.

No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publisher, GlobalData.

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