EU/3/10/760 - orphan designation for treatment of ovarian cancer

(3S)-3-{4-[7-(aminocarbonyl)-2H-indazol-2-yl] phenyl} piperidine tosilate monohydrate salt (niraparib)

Overview

On 4 August 2010, orphan designation (EU/3/10/760) was granted by the European Commission to Merck Sharp & Dohme Limited, United Kingdom, for (3S)-3-{4-[7-(aminocarbonyl)-2H-indazol-2-yl] phenyl} piperidine tosylate monohydrate salt (also known as MK-4827) for the treatment of ovarian cancer. (3S)-3-{4-[7-(aminocarbonyl)-2H-indazol-2-yl] phenyl} piperidine tosylate monohydrate salt has been authorised in the EU as Zejula since 16 November 2017.

This medicine is now known as niraparib.

The sponsorship was transferred to Tesaro U.K. Limited, United Kingdom, in December 2012.

The sponsorship was transferred to TESARO Bio Netherlands B.V. in December 2018.

The sponsorship was transferred to GlaxoSmithKline (Ireland) Limited., Ireland, in December 2019.

What is ovarian cancer?

Ovarian cancer is cancer of the ovaries (two organs in the female reproductive system that produce eggs). Most ovarian cancers occur in women over the age of 50 years. Due to the absence of symptoms in the early stages of the disease, the majority of patients are diagnosed when the cancer has spread locally or to other parts of the body.

Ovarian cancer is a life-threatening disease that is associated with poor long-term survival.

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

At the time of designation, ovarian cancer affected approximately 2.9 in 10,000 people in the European Union (EU). This was equivalent to a total of around 147,000 people*, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based 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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 506,300,000 (Eurostat 2010).

What treatments are available?

At the time of designation, several medicines were authorised in the EU for the treatment of ovarian cancer. The choice of treatment depended mainly on how advanced the disease was. Treatments included surgery and chemotherapy (medicines to treat cancer).

The sponsor has provided sufficient information to show that (3S)-3-{4-[7-(aminocarbonyl)-2H-indazol-2-yl] phenyl} piperidine tosylate monohydrate salt might be of significant benefit for patients with ovarian cancer because it works in a different way to existing treatments, and early studies indicate that it might be used in combination with existing treatment to improve the outcome of patients with this condition. 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?

This medicine is expected to work by blocking some enzymes known as poly(ADP-ribose) polymerase (PARP)-1 and -2. These enzymes are used to repair damaged DNA. By blocking PARP-1 and -2, the medicine prevents cancer cells from repairing their DNA, eventually killing them. It is expected that the medicine will be able to be used on its own to kill those cancer cells that do not have other ways of repairing DNA damage, such as those with abnormalities in the BRCA-1 or BRCA-2 genes, which are found in some ovarian cancer patients. The medicine is also expected to be used in combination with other cytotoxic (cell-killing) cancer medicines that cause DNA damage, where it is expected to enhance their activity by preventing DNA repair.

What is the stage of development of this medicine?

The effects of this medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with ovarian cancer were planned.

At the time of submission, this medicine was not authorised anywhere in the EU for ovarian cancer or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 May 2010 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.

EU/3/10/760: Public summary of opinion on orphan designation of (3S)-3-{4-[7-(aminocarbonyl)-2H-indazol-2-yl] phenyl} piperidine tosylate monohydrate salt for the treatment of ovarian cancer

AdoptedReference Number: EMA/COMP/325300/2010

Key facts

• Active substance:
  (3S)-3-{4-[7-(aminocarbonyl)-2H-indazol-2-yl] phenyl} piperidine tosilate monohydrate salt (niraparib)
• Intended use:
  Treatment of ovarian cancer
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/10/760
• Date of designation:
  04/08/2010
• Sponsor:

  GlaxoSmithKline (Ireland) Limited; 12 Riverwalk; Citywest Business Campus; Dublin 24; D24 YK11; Ireland; E-mail: [e-mail]

Review of designation

The Committee for Orphan Medicinal Products reviewed the orphan designation of Zejula at the time of change to the terms of the marketing authorisation, and confirmed that the orphan designation should be maintained. 

More information is available in the Zejula : Orphan maintenance assessment report (post-authorisation) (II-019). 

During its meeting of 3 to 5 October 2017, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/10/760 for Zejula (niraparib¹)as an orphan medicinal product for the treatment of ovarian cancer. 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 ovarian cancer.The COMP recommended that the orphan designation of the medicine be maintained².

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¹ Previously known as (3S)-3-{4-[7-(aminocarbonyl)-2H-indazol-2-yl] phenyl} piperidine tosylate monohydrate salt.

²The 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.