ZUG, Switzerland, April 26, 2017 /PRNewswire/ --
Natpar is the first and
only licensed recombinant human
parathyroid hormone therapy for chronic
hypoparathyroidism
Shire plc (LSE: SHP, NASDAQ: SHPG) today announced that the
European Commission (EC) has granted Conditional Marketing
Authorisation for Natpar (rhPTH[1-84]), the first recombinant human
protein with the full length 84-amino acid sequence of endogenous
parathyroid hormone (PTH). Natpar will be the first and only
approved hormone therapy indicated as adjunctive treatment for
adult patients with chronic hypoparathyroidism who cannot be
adequately controlled with standard therapy
alone.[1] Hypoparathyroidism is a
rare endocrine disease resulting from an inappropriately low
circulating PTH
concentration.[2]
'‘As the first and only licensed recombinant
parathyroid hormone treatment in Europe for chronic hypoparathyroidism, Natpar
represents a historical and timely innovation for patients who
cannot be adequately controlled on calcium and vitamin D alone,"
said Philip J. Vickers, Ph.D.,
Global Head of Research and Development at Shire. "The approval of
Natpar offers an important advance in the management of this rare
endocrine disorder for patients in Europe."
The Conditional Marketing Authorisation is based on the outcomes
from the Phase III efficacy and safety of rhPTH(1-84) clinical
trial (REPLACE) in patients aged 19-74 years with chronic
hypoparathyroidism.[1] The trial
showed that Natpar maintained serum calcium while reducing oral
calcium and active vitamin D supplemental
doses.[1]
"Chronic hypoparathyroidism can carry a significant disease
burden, and some patients are not well-controlled, showing
fluctuations in their serum calcium
levels,[3]" said Professor
Maria Louisa Brandi, Department of
Internal Medicine, University of Florence, Italy. "Clinical studies have shown
Natpar maintains serum calcium while reducing the need for calcium
and vitamin D for patients with chronic
hypoparathyroidism.[1]"
With this approval, Shire is now authorized to market Natpar in
the 28 Member States of the European Union (EU), as well as in
Iceland, Liechtenstein and Norway. Natpar falls under the scope of
European Commission Regulation as eligible for Conditional
Marketing Authorisation because it is designated as an orphan
medicinal product and fulfils an unmet medical need.
About hypoparathyroidism
Hypoparathyroidism is a rare disease that occurs when inadequate
levels of 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.
Guidelines from the European Society of Endocrinology (ESE)
state that a diagnosis of chronic hypoparathyroidism should be
considered in a patient with hypocalcemia and an inappropriately
low PTH concentration. Guidelines recommend that treatment should
aim to restore mineral homeostasis and prevent symptoms of
hypocalcemia while optimizing overall well-being. Typical symptoms
of hypocalcemia include muscle spasms and cramping.
To date, management of chronic hypoparathyroidism has focused on
maintaining serum calcium with oral calcium and active vitamin D
supplements; however, some patients are not adequately controlled
and still have variations in their serum calcium
levels.[3]-[6]
About Natpar
Natpar is a recombinant human PTH and will be available as a 25,
50, 75 and 100 micrograms once-daily injection as adjunctive
treatment for adult patients with chronic hypoparathyroidism who
cannot be adequately controlled with standard therapy alone.
Natpar is approved in the United
States under the trade name Natpara® (parathyroid
hormone).
About the REPLACE study
In the double-blind, placebo-controlled, randomized Phase III
study 124 patients with hypoparathyroidism were randomized in a
ratio of 2:1 to either 50 micrograms once daily of rhPTH(1-84) or
placebo for 24 weeks. The primary endpoint was a 50 percent or
greater reduction from baseline in their daily dose of oral calcium
and active vitamin D while maintaining a stable albumin corrected
serum calcium concentration greater than or equal to baseline
concentration (baseline was 2.1 mmol/L for the rhPTH[1-84] group
and 2.2 mmol/L for the placebo group) and less or equal to the
upper limit of normal (normal range 2.1-2.6 mmol/L). At the end of
the treatment period, 54.8 percent of the patients on rhPTH(1-84)
achieved the primary endpoint compared with 2.5 percent of patients
in the placebo group
(p<0.0001).[1] There were no
differences in the proportion of patients maintaining a stable
albumin corrected serum calcium concentration at the end of
treatment between subjects randomized to rhPTH (1-84) and
placebo.[7]
Natpar Safety Information for Europe
Please consult the Natpar Summary Product Characteristics (SmPC)
before prescribing.
Natpar treatment should be supervised by a physician or other
qualified healthcare professional experienced in the management of
patients with hypoparathyroidism.
Contraindications
Natpar is contraindicated in patients with hypersensitivity to the
active substance or to any of the excipients, who are receiving or
who have previously received radiation therapy to the skeleton,
with skeletal malignancies or bone metastases, who are at increased
baseline risk for osteosarcoma, with unexplained elevations of
bone-specific alkaline phosphatase, with pseudohypoparathyroidism.
Warnings and Precautions
Monitoring of patients during treatment pre-dose and in some
cases post-dose serum calcium levels must be monitored during
treatment with Natpar.
Hypercalcemia this was reported in clinical trials with Natpar.
Hypercalcemia commonly occurred during the titration period, during
which doses of oral calcium, active vitamin D, and Natpar were
being adjusted. Hypercalcemia may be minimized by following the
recommended dosing, the monitoring information and asking patients
about any symptoms of hypercalcemia. If severe hypercalcemia
develops, hydration and temporarily stopping Natpar, calcium and
active vitamin D should be considered until serum calcium returns
to the normal range. Then consider resuming Natpar, calcium and
active vitamin D at lower doses.
Hypocalcemia a common clinical manifestation of
hypoparathyroidism, was reported in clinical trials with Natpar.
Most of the hypocalcemic events occurring in the clinical trials
were mild to moderate severity. The risk for serious hypocalcemia
was greatest after the withdrawal of Natpar. Temporary or permanent
discontinuation of Natpar must be accompanied by monitoring of
serum calcium levels and increase of exogenous calcium and/or
vitamin D sources as necessary. Hypocalcemia may be minimized by
following the recommended dosing, the monitoring information, and
asking patients about any symptoms of hypocalcemia.
Concomitant use with cardia glycosides Hypercalcaemia of any
cause may predispose to digitalis toxicity, monitor serum calcium
and cardiac glycoside levels and patients for signs and symptoms of
digitalis toxicity.
Severe renal or hepatic disease Natpar should be used with
caution in patients with severe renal or hepatic disease because
they have not been evaluated in clinical trials.
Use in young adults Natpar should be used with caution in young
adult patients with open epiphyses.
Tachyphylaxis the calcium-raising effect of Natpar may diminish
over time in some patients. The response of serum calcium
concentration to administration of Natpar should be monitored at
intervals to detect this and the diagnosis of tachyphylaxis
considered.
Adverse Reactions
The most commonly observed adverse events with Natpar
treatment were hypercalcaemia, hypocalcaemia, headache, diarrhea,
vomiting, paraesthesia, hypoesthesia and hypercalciuria.
Very common
(frequency Hypercalcemia, hypocalcaemia, headache, hypoesthesia,
greater than or paraesthesia, diarrhoea, nausea, vomiting, arthralgia, and
equal to1/10): muscle spasms.
Common Hypomagnesaemia, tetany, anxiety, insomnia, somnolence,
palpitations, hypertension, cough, abdominal pain upper,
muscle twitching, musculoskeletal pain, myalgia, neck pain,
pain in extremity, hypercalciuria, pollakiuria, asthenia,
(greater than or chest pain, fatigue, injection site reactions, thirst,
equal to1/100 to anti-PTH antibody positive, blood 25-hydroxycholecalciferol
<1/10): decreased, vitamin D decreased.
NOTES TO EDITORS
About Shire
Shire is the leading global biotechnology company focused on
serving people with rare diseases and other highly specialized
conditions. We strive to develop best-in-class products, many of
which are available in more than 100 countries, across core
therapeutic areas including Hematology, Immunology, Neuroscience,
Ophthalmics, Lysosomal Storage Disorders, Gastrointestinal /
Internal Medicine / Endocrine and Hereditary Angioedema; and a
growing franchise in Oncology.
Our employees come to work every day with a shared mission: to
develop and deliver breakthrough therapies for the hundreds of
millions of people in the world affected by rare diseases and other
high-need conditions, and who lack effective therapies to live
their lives to the fullest.
http://www.shire.com
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result of governmental regulations and market developments may
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Some of Shire's products or ingredients are only available from a
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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;
- certain of Shire's therapies involve lengthy and complex
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and development. The successful development of these products is
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and there is no guarantee that these products will receive
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Shire's revenues, financial conditions or results of
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could have a material adverse effect on the Company's revenues,
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- failure to achieve the strategic objectives, including expected
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synergies or other benefits at the time anticipated or at all with
respect to Shire's acquisitions, including NPS Pharmaceuticals
Inc., Dyax Corp. or Baxalta Incorporated may adversely affect
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- 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
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impact the availability and cost of credit and customer purchasing
and payment patterns, including the collectability of customer
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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 incurred substantial additional indebtedness to finance
the Baxalta acquisition, which may decrease its business
flexibility and increase borrowing costs; 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 "ITEM 1A: 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
- Natpar® Summary of Product Characteristics.
- Bilezikian JP, et al. J Clin Endocrinol Metab.
2016;101:2313-2324.
- Mitchell DM, et al. J Clin Endocrinol Metab.
2012;97:4507-4514.
- Bollerslev J, et al. Eur J Endocrinol. 2015;173:G1-G20.
- Brandi ML, et al. J Clin Endocrinol Metab.
2016;101:2273-2283.
- Hadker N, et al. Endocr Pract. 2014;20:671-679.
- Mannstadt M, et al. Lancet Diabetes Endocrinol.
2013;1:275-283.
For further information, please contact:
Investor Relations
Ian Karp
ikarp@shire.com
+1-781-482-9018
Robert Coates
rcoates@shire.com
+44(0)1256-894874
Media
Annabel Cowper
annabel.cowper@shire.com
+41-79-630-8619
Debbi Ford
debbi.ford@shire.com
+1-617-949-9083