EU/3/13/1210

On 16 January 2014, orphan designation (EU/3/13/1210) was granted by the European Commission to NPS Pharma UK Ltd, United Kingdom, for recombinant human parathyroid hormone for the treatment of hypoparathyroidism.

The sponsorship was transferred to Shire Pharmaceuticals Ireland Limited, Ireland, in January 2016.

Recombinant human parathyroid hormone has been authorised in the EU as Natpar since 24 April 2017.

What is hypoparathyroidism?

Hypoparathyroidism is a hormone disorder where the parathyroid glands in the neck produce too little parathyroid hormone, in most cases because of damage to the parathyroid glands during surgery. Parathyroid hormone helps to regulate levels of calcium and phosphate in the body; too little of it may result in too little calcium and too much phosphate in the blood, which can produce effects on bones, nerves and muscles, including paraesthesia (tingling sensations), weakening of the bones, muscle spasms, seizures (fits) and abnormal heart beats and damage to heart muscle.

Hypoparathyroidism is a debilitating disease that is long lasting and may be life threatening due to the effects of low blood-calcium.

What is the estimated number of patients affected by the condition?

At the time of designation, hypoparathyroidism affected less than 5 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 256,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 28), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 512,900,000 (Eurostat 2014).

What treatments are available?

At the time of designation, hypoparathyroidism was treated in the EU with calcium and vitamin D supplements; thiazide diuretics (a class of medicines that increase the production of urine) were also used because of their ability to lower the amount of calcium that is eliminated in the urine.

The sponsor has provided sufficient information to show that recombinant human parathyroid hormone might be of significant benefit for patients with hypoparathyroidism because it replaces the hormone that is missing, thus easing the symptoms of the disease. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

Recombinant human parathyroid hormone is identical to the hormone naturally produced by the body. This medicine replaces the missing hormone and is expected to restore the body’s levels of calcium and phosphate.

The medicine is made by a method known as ‘recombinant DNA technology’: it is made by cells into which a gene (DNA) has been introduced that makes them able to produce human parathyroid hormone.

What is the stage of development of this medicine?

The effects of recombinant human parathyroid hormone have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicinal product in patients with hypoparathyroidism had finished.
At the time of submission, this medicine was authorised in the EU for the treatment of osteoporosis.

At the time of submission, this medicine was not authorised anywhere in the EU for hypoparathyroidism. Orphan designation of recombinant human parathyroid hormone had been granted in the United States for the treatment of hypoparathyroidism.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 November 2013 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.

On 6 March 2017, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/13/1210 for Natpar (parathyroid hormone) as an orphan medicinal product for the treatment of hypoparathyroidism. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other methods of treatment. As other methods of treatment are authorised in the European Union (EU), the COMP also considered whether the medicine is of significant benefit to patients with treatment of hypoparathyroidism. The COMP recommended that the orphan designation of the medicine be maintained¹

¹ The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with the same therapeutic indication cannot be placed on the market.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Natpar for the ‘adjuvant treatment of adult patients with chronic hypoparathyroidism who cannot be adequately controlled with standard therapy alone’.

This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of hypoparathyroidism’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2013. Hypoparathyroidism remains a debilitating and life-threatening condition because low levels of calcium can lead to problems with the bones, muscles, heart, kidneys and other parts of the body.

Prevalence of the condition

The sponsor provided updated information on the prevalence of hypoparathyroidism based on data from the published literature, the General Practice Registry of the UK and the US Health Analytics MarketScan Research Databases.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of hypoparathyroidism remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was estimated to be approximately 3.5 people in 10,000. This is equivalent to a total of around 180,000 people in the EU.

Existence of other methods of treatment

At the time of the review of the orphan designation, calcium and vitamin D supplements were authorised in the EU for the treatment of hypoparathyroidism. Some patients were also treated with thiazide diuretics to lower the amount of calcium that is eliminated in the urine.

Significant benefit of Natpar

The COMP concluded that the claim of a significant benefit of Natpar in hypoparathyroidism is justified on the basis of clinical data showing that Natpar helps control blood calcium levels, reducing the need for calcium and vitamin D supplements, which may lead to complications when used at high doses.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Natpar is of significant benefit to patients affected by hypoparathyroidism.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Natpar still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.

Further information on Natpar can be found in the European public assessment report (EPAR).