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Takeda Presents New Data at the Endocrine Society’s 2019 Annual Meeting about the Patient Burden and Long-Term Impact of Chronic Hypoparathyroidism

March 26, 2019 Off By BusinessWire

Impact on patient quality of life quantified including long-term
renal and cardiovascular complications
Final outcomes of 6 year study into continuous use of rhPTH(1-84)
shows improvements in key measurements of mineral homeostasis

OSAKA, Japan–(BUSINESS WIRE)–Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK)
(“Takeda”) this week shared new data revealing the burden of chronic
hypoparathyroidism on patients and caregivers, as well as potential
long-term risks of renal and cardiovascular complications that patients
treated with conventional therapy may experience. Six-year results from
the open-label long-term safety and efficacy RACE study were also
announced. Data was presented at the Endocrine Society’s 2019 Annual
Meeting (ENDO) from 23–26 March in New Orleans, Louisiana, USA.

“Results from the Burden of Illness Global Survey in 13 countries reveal
the extent of the impact hypoparathyroidism has on patients and their
caregivers throughout their daily lives,” said John Bilezikian M.D.,
Professor of Medicine at the Columbia University Irving Medical Center,
New York, NY, USA. “This offers important insights and enables us to
take a more holistic approach in the management of these patients due to
a greater understanding of the potential cardiovascular risks patients
may face, along with other complications of the kidneys,” he added.

“We are committed to further investigating this rare condition and
collecting more data on the long-term implications,” said John Germak,
Global Medical Team Lead at Takeda. “Gaining valuable insights directly
from patients enhances our understanding of the complex nature of the
disease and its management. The data presented at ENDO supports this
cause.”

Three abstracts from the Burden of Illness Global Survey were presented
for the first time at ENDO. The multi-country self-reported survey, the
first large study of its kind, looked at physical and mental health
components to characterise the burden and impact of the disease. Results
showed substantial symptom burden and health-related quality of life
impact in patients with chronic hypoparathyroidism not adequately
controlled with conventional therapy, and their caregivers.^1,2,3

New data on the risk of chronic kidney disease (CKD) and its progression
were also presented alongside a study investigating estimated glomerular
filtration rate (eGFR) decline in patients with chronic
hypoparathyroidism. Furthermore, results from a new study looking at the
risk of cardiovascular conditions in patients with chronic
hypoparathyroidism – an area of limited prior research – were shared.^4,5,6,7

Final results from the six-year RACE study, with efficacy endpoints of
calcium dose reduction, reduction in calcitriol dose and normalization
or maintaining serum calcium, reported data in key measurements of
mineral homeostasis in chronic hypoparathyroidism patients treated with
recombinant human parathyroid hormone rhPTH (1-84).In
addition, results from this study reported a safety profile consistent
with previous clinical trials results.⁸

Takeda presented a total of eight abstracts at the congress further
building on the company’s knowledge and experience of the disease.

All abstracts are available on the ENDO 2019 website at https://www.abstractsonline.com/pp8/#!/5752

About the Data

Burden of Illness Global Patient and Caregivers Survey^1,2,3
The
survey data showed patients experience substantial symptom burden
including physical fatigue (97%), muscle cramps (86%), tingling (84%),
brain fog (77%), anxiety (78%) and depression (76%). The magnitude of
symptom severity correlated with the impact on the reduction in
patients’ health-related quality of life.

Patients also reported an impact on their lifestyle through a symptom
diary, showing an effect on sleep (78%), the ability to exercise (84%),
ability to work (75%) as well as an impact on family relationships
(63%). In turn, caregivers reported a major impact on their relationship
with spouse/partner, family and friends.

Long-term Complications Associated with Chronic Hypoparathyroidism^4,5,6,7,13
Four
studies were presented. Results from a study investigating the
risk of CKD and its progression, a retrospective controlled cohort study
comparing risks in chronic and non-hypoparathyroidism patients, showed
that patients with chronic hypoparathyroidism on conventional therapy
had a significantly increased risk of developing CKD stage 3 and
greater, as well as progression to end stage renal disease. In addition,
eGFR – a key indicator of kidney function¹³ – was examined
and an association with chronic hypoparathyroidism and increased rate of
eGFR decline over time was observed in the subset of cohorts with
laboratory data available. Moreover, hypoparathyroid patients had an
increased risk of nephrolithiasis and nephrocalcinosis compared with
matched controls of patients without hypoparathyroidism.

In another retrospective cohort study, to compare the risk of
cardiovascular (CV) conditions in patients with chronic
hypoparathyroidism and non-hypoparathyroidism patients, the database
analysis showed that chronic hypoparathyroidism patients had an
increased risk of experiencing a new occurrence of each of the
cardiovascular conditions studied, as well as the composite
cardiovascular endpoints of cerebrovascular disease, coronary artery
disease, peripheral artery disease and heart failure, compared to
patients without hypoparathyroidism.

These studies, presented for the first time at ENDO, employed a
systematic way to examine risk associations between long-term
complications and chronic hypoparathyroidism. Although considered
hypothesis generating and further research is warranted, the findings
provide valuable new data and additional learnings for this rare
condition.

RACE 6-year Long-term Safety and Efficacy of rhPTH (1-84)⁸
Six-year
results from the open-label RACE study presented at ENDO showed that
treatment with rhPTH (1-84) in patients with chronic hypoparathyroidism
had a safety profile consistent with previous clinical studies, and
impacted key measurements of mineral homeostasis, notably of urinary
calcium. Albumin-corrected serum calcium levels remained within the
target range, stable urinary calcium excretion, serum phosphate, serum
creatinine, and eGFR was observed and doses of oral calcium and
calcitriol were reduced by >40% and >70% compared to baseline.

About Hypoparathyroidism
Hypoparathyroidism is a rare
endocrine disease which occurs when inadequate levels of parathyroid
hormone (PTH) are secreted by the parathyroid glands in the neck,
resulting in a mineral imbalance in the body.^9,10,11 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 to be
chronic.^10,12Chronic hypoparathyroidism can have a
significant impact on patients’ health-related quality of life, as well
as leading to serious long-term complications.

About NATPARA^® (parathyroid hormone) for
Injection in the U.S.
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.¹⁴ 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.

About NATPAR^®for Injection in Europe
NATPARA
is approved in Europe under the tradename NATPAR^®. NATPAR
is indicated as adjunctive treatment of adult patients with chronic
hypoparathyroidism who cannot be adequately controlled with standard
therapy alone.¹⁵ Takeda is authorised to market
NATPAR in the 28 Member States of the European Union, as well as in
Iceland, Liechtenstein and Norway. NATPAR is currently commercially
available in Germany, Greece, Austria, Denmark and Norway.

U.S. 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.

For more information about the NATPARA REMS program, call
1-855-NATPARA or go to www.NATPARAREMS.com.

Contraindications
NATPARA is contraindicated in patients
with a known hypersensitivity to any component of NATPARA.
Hypersensitivity reactions (e.g., anaphylaxis, angioedema, and
urticaria) have occurred with NATPARA.

Warnings and Precautions
Hypercalcemia: Severe
hypercalcemia has been reported with NATPARA. The risk is highest when
starting or increasing the dose of NATPARA but can occur at any time.
Monitor serum calcium and patients for signs and symptoms of
hypercalcemia. Treat hypercalcemia per standard practice and consider
holding and/or lowering the dose of NATPARA if severe hypercalcemia
occurs.

Hypocalcemia: Severe hypocalcemia has been reported in
patients taking NATPARA, including cases that resulted in seizures. The
risk is highest with interruption or discontinuation of NATPARA
treatment but can occur at any time. Monitor serum calcium and patients
for signs and symptoms of hypocalcemia, and replace calcium and vitamin
D if indicated in patients interrupting or discontinuing NATPARA to
prevent severe hypocalcemia.

Digoxin Toxicity: 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.

Hypersensitivity: There have been reports of
hypersensitivity reactions in patients taking NATPARA. Reactions
included anaphylaxis, dyspnea, angioedema, urticaria, and rash. If signs
or symptoms of a serious hypersensitivity reaction occur, discontinue
treatment with NATPARA, treat hypersensitivity reaction according to the
standard of care, and monitor until signs and symptoms resolve. Monitor
for hypocalcemia if NATPARA is discontinued.

Adverse Reactions
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.

Drug Interactions
Alendronate:
Co-administration of alendronate and NATPARA leads to reduction in the
calcium sparing effect, which can interfere with the normalization of
serum calcium. Concomitant use of NATPARA with alendronate is not
recommended.

Use in Specific Populations
There are no adequate and
well-controlled studies in pregnant women. Use during pregnancy only if
the potential benefit justifies the potential risk to the fetus.

The safety and efficacy in pediatric patients have not been established.

Click here for the full U.S. Prescribing Information:
http://www.shirecontent.com/PI/PDFs/Natpara_USA_ENG.pdf

Click here for the full European Prescribing Information:
https://www.ema.europa.eu/en/documents/product-information/natpar-epar-product-information_en.pdf

About Takeda Pharmaceutical Company Limited
Takeda
Pharmaceutical Company Limited (TSE:4502/NYSE:TAK)
is a global, values-based, R&D-driven biopharmaceutical leader
headquartered in Japan, committed to bringing Better Health and a
Brighter Future to patients by translating science into
highly-innovative medicines. Takeda focuses its R&D efforts on four
therapeutic areas: Oncology, Gastroenterology (GI), Neuroscience, and
Rare Diseases. We also make targeted R&D investments in Plasma-Derived
Therapies and Vaccines. We are focusing on developing highly innovative
medicines that contribute to making a difference in people’s lives by
advancing the frontier of new treatment options and leveraging our
enhanced collaborative R&D engine and capabilities to create a robust,
modality-diverse pipeline. Our employees are committed to improving
quality of life for patients and to working with our partners in health
care in approximately 80 countries and regions.
For more
information, visit https://www.takeda.com

References
1. Impact of Chronic Hypoparathyroidism on
Health-Related Quality of Life: Findings from a 13-Country Patient
Survey. Siggelkow et al., ENDO, March 2019. Available at: https://www.abstractsonline.com/pp8/#!/5752/presentation/15405
2.
Symptoms, Comorbidities and Treatment Satisfaction with Chronic
Hypoparathyroidism: Findings from a 13-Country Patient Survey.
Bollerslev et al., ENDO, March 2019. Available at: https://www.abstractsonline.com/pp8/#!/5752/presentation/15404
3.
Impact of Chronic Hypoparathyroidism on Word, Productivity, and
relationships: Findings from a 13-Country Patient and Caregiver Survey.
Clarke et al. ENDO, March 2019. Available at: https://www.abstractsonline.com/pp8/#!/5752/presentation/15403
4.
Risk of Chronic Kidney disease (CKD) and Its Progression in Patients
with Chronic Hypoparathyroidism (HypoPT). Chen et al. ENDO, March 2019.
Available at: https://www.abstractsonline.com/pp8/#!/5752/presentation/15406
5.
Risk of Decline in Estimated Glomerular Filtration Rate (eGFR) in
Patients with Chronic Hypoparathyroidism (HypoPT). Chen et al, ENDO,
March 2019. Available at: https://www.abstractsonline.com/pp8/#!/5752/presentation/15408
6.
Risk of Cardiovascular (CV) Conditions in Patients with Chronic
Hypoparathyroidism (HypoPT). Chen et al. ENDO, March 2019. Available
at: https://www.abstractsonline.com/pp8/#!/5752/presentation/15410
7.
Risk of Nephrolithiasis and Nephrocalcinosis in Patients with Chronic
Hypoparathyroidism (HypoPT). Chen et al. ENDO, March 2019. Available
at: https://www.abstractsonline.com/pp8/#!/5752/presentation/15407
8.
Safety and Efficacy of Recombinant Human Parathyroid Hormone 1-84 for
the Treatment of Adults with Chronic Hypoparathyroidism: Six-Year
Results of the RACE study. Bilezikian, et al. ENDO, March 2019.
Available at: https://www.abstractsonline.com/pp8/#!/5752/presentation/16334
9.
Shoback DM, et al. J Clin Endocrinol Metab. 2016;101(6):2300–12.
10.
Bollerslev J, et al. Eur J Endocrinol. 2015;173:G1–G20.
11. Hadker
N, et al. Endocr Pract. 2014;20(7):671–9.
12. Brandi et al. J Clin
Endocrinol Metab. 2016;101:2273–83.
13. National Kidney Foundation.
Glomerular Filtration Rate (GFR). Available at: https://www.kidney.org/sites/default/files/docs/11-10-1813_abe_patbro_gfr_b.pdf
Accessed: Jan 2019
14. Natpara® Highlights of prescribing
information. Initial US approval: 2015. Available at: http://www.shirecontent.com/PI/PDFs/Natpara_USA_ENG.pdf.
Accessed Jan 2019
15. Natpar® Summary of Product
Characteristics.