EU/3/06/403

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Orphan designation

On 23 October 2006, orphan designation (EU/3/06/403) was granted by the European Commission to Theraptosis, France, for 5-(2,6-Difluoro-phenoxy)-3(R,S)-{2(S)-[2(S)-(3-methoxycarbonyl-2(S)-{3-methyl-2(S)-[(quinoline-2-carbonyl)-amino]-butyrylamino}-propionylamino)-3-methyl-butyrylamino]-propionylamino}-4-oxo-pentanoic acid methyl ester for the treatment of neonatal brain injury.

The sponsorship was transferred to Chiesi Farmaceutici S.P.A., Italy, in February 2010.

What is neonatal brain injury?

Neonatal brain injury refers to damage to certain parts of the developing brain. This damage can occur early in pregnancy when the brain is forming, during the birth process or after birth in the first few days to weeks of life. In many cases, the exact cause of the brain damage is not known. The severity of the injury varies widely, from very mild and subtle to very profound. In its severe form, it leads to damage in one or more parts of the brain that control muscle tone and motor activity (movement) and then is called cerebral palsy. These infants are usually slow to reach developmental milestones such as rolling over, sitting, crawling, and walking.

Another possible sign of neonatal brain injury is known as neonatal seizures. These occur within 28 days of birth but often no typical convulsions are detected. Instead, for example their eyes appear to be looking in different directions; or they may have lip smacking or periods of no breathing.

Neonatal brain injury is a life-threatening and chronically debilitating condition.

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

At the time of designation, neonatal brain injury affected less than 1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 46,000 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 knowledge of the Committee for Orphan Medicinal Products (COMP).

*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 25), Norway, Iceland and Liechtenstein. This represents a population of 459,700,000 (Eurostat 2004).

What treatments are available?

No satisfactory methods exist that were authorised at the time of application.

How is this medicine expected to work?

5-(2,6-Difluoro-phenoxy)-3(R,S)-{2(S)-[2(S)-(3-methoxycarbonyl-2(S)-{3-methyl-2(S)-[(quinoline-2-carbonyl)-amino]-butyrylamino}-propionylamino)-3-methyl-butyrylamino]-propionylamino}-4-oxo-pentanoic acid methyl ester has been shown to inhibit the function of a cell molecule, called caspase-2. The latter is one of a series of specific enzymes (a type of protein) involved in the “programmed death” of cells. By inhibiting this enzyme, the proposed medicinal product aims to prevent the process of programmed brain cell (neuronal) death, associated with neonatal brain injury. The goal of this treatment is to limit long-term adverse (negative) consequences to proper brain functioning.

What is the stage of development of this medicine?

The evaluation of the effects of 5-(2,6-Difluoro-phenoxy)-3(R,S)-{2(S)-[2(S)-(3-methoxycarbonyl-2(S)-{3-methyl-2(S)-[(quinoline-2-carbonyl)-amino]-butyrylamino}-propionylamino)-3-methyl-butyrylamino]-propionylamino}-4-oxo-pentanoic acid methyl ester in experimental models is ongoing.

At the time of submission of the application for orphan designation, no clinical trials in patients with neonatal brain injury were initiated.

5-(2,6-Difluoro-phenoxy)-3(R,S)-{2(S)-[2(S)-(3-methoxycarbonyl-2(S)-{3-methyl-2(S)-[(quinoline-2-carbonyl)-amino]-butyrylamino}-propionylamino)-3-methyl-butyrylamino]-propionylamino}-4-oxo-pentanoic acid methyl ester was not authorised anywhere worldwide for neonatal brain injury or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 September 2006 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 Community) 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.

Key facts

Product details for <p>5-(2,6-Difluoro-phenoxy)-3(R,S)-{2(S)-[2(S)-(3-methoxycarbonyl-2(S)-{3-methyl-2(S)-[(quinoline-2-carbonyl)-amino]-butyrylamino}-propionylamino)-3-methyl-butyrylamino]-propionylamino}-4-oxo-pentanoic acid methyl ester</p>
Active substance5-(2,6-Difluoro-phenoxy)-3(R,S)-{2(S)-[2(S)-(3-methoxycarbonyl-2(S)-{3-methyl-2(S)-[(quinoline-2-carbonyl)-amino]-butyrylamino}-propionylamino)-3-methyl-butyrylamino]-propionylamino}-4-oxo-pentanoic acid methyl ester
Medicine Name
Disease/conditionTreatment of neonatal brain injury
Date of decision23/10/2006
OutcomePositive
Orphan decision numberEU/3/06/403

Review of designation

Sponsor’s contact details:

Chiesi Farmaceutici S.P.A.
Via Palermo 26/A
43100 Parma
Italy
Telephone: + 39 0521 2791
Telefax: + 39 0521 77 41 20
E-mail: info@chiesigroup.com

Patients’ association contact point

For contact details of patients’ organisations whose activities are targeted at rare diseases see:

  • Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe.
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.