EU/3/12/976

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Orphan designation

This medicine is now known as nusinersen

On 2 April 2012, orphan designation (EU/3/12/976) was granted by the European Commission to Isis USA Ltd, United Kingdom, for antisense oligonucleotide targeted to the SMN2 gene for the treatment of 5q spinal muscular atrophy.

In April 2016, Isis USA Ltd changed name to Ionis USA Ltd.

The sponsorship was transferred to Biogen Idec Ltd, United Kingdom, in August 2016.

Update: Antisense oligonucleotide targeted to the SMN2 gene has been authorised in the EU as Spinraza since 30 May 2017.

What is 5q spinal muscular atrophy?

5q spinal muscular atrophy is an inherited disease that affects the motor neurons (nerves from the brain and spinal cord that control muscle movements). Patients with the disease lack a protein called ‘survival motor neuron’ (SMN), which is essential for the normal functioning and survival of motor neurons. Without this protein, the motor neurons deteriorate and eventually die. This causes the muscles to fall into disuse, leading to muscle wasting (atrophy) and weakness. Muscle weakness is usually more severe in the proximal musculature (the muscles closest to the trunk). The disease is linked to a defect on chromosome 5q and is usually diagnosed in the first year of life.

5q spinal muscular atrophy is a long-term debilitating and life-threatening disease because it causes breathing problems and paralysis that worsens over time.

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

At the time of designation, 5q spinal muscular atrophy affected less than 0.4 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 20,000 people, and is below the ceiling 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).


*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. This represents a population of 506,300,000 (Eurostat 2011).

What treatments are available?

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of 5q spinal muscular atrophy. Patients received supportive treatment to help them and their families cope with the symptoms of the disease. This included chest physiotherapy and physical aids to support muscular function, and ventilators to help with breathing.

How is this medicine expected to work?

The SMN protein is made by two genes, the SMN1 and SMN2 genes. Most patients with 5q spinal muscular atrophy lack the SMN1 gene but have the SMN2 gene, which mostly produces a ‘short’ SMN protein which cannot work properly.

This medicine is an ‘anti-sense oligonucleotide’ medicine. It is expected to make the SMN2 gene produce adequate levels of the SMN protein of normal length, thereby increasing the survival of motor neurons. It is expected to do so by blocking the cutting (‘splicing’) of the molecule produced from the SMN2 gene that serves as the ‘template’ for the SMN protein. This is expected to lead to an increased production of the normal-length SMN protein.

This medicine is expected to be given by injection into the fluid surrounding the spinal cord and brain.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicinal product in experimental models was ongoing.

At the time of submission, no clinical trials with the medicinal product in patients with 5q spinal muscular atrophy had been started.

At the time of submission, the medicinal product was not authorised anywhere in the EU for the treatment of 5q spinal muscular atrophy. Orphan designation of the medicinal product had been granted in the United States of America for the treatment of 5q spinal muscular atrophy.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 February 2012 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.

Key facts

Product details for <p>Antisense oligonucleotide targeted to the <em>SMN2</em> gene <span style="FONT-SIZE: 9pt; FONT-FAMILY: ">(nusinersen)</span></p>
Active substanceAntisense oligonucleotide targeted to the SMN2 gene (nusinersen)
Medicine Name
Disease/conditionTreatment of 5q spinal muscular atrophy
Date of decision02/04/2012
OutcomePositive
Orphan decision numberEU/3/12/976

Review of designation

On 25 April 2017, the Committee for Orphan Medicinal Products (COMP) concluded its review of the designation EU/3/12/976 for Spinraza (nusinersen, previously known as antisense oligonucleotide targeted to the SMN2 gene) as an orphan medicinal product for the treatment of 5q spinal muscular atrophy. 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. The COMP recommended that the orphan designation of the medicine be maintained1.


1The 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 Spinraza for: ‘treatment of 5q spinal muscular atrophy (SMA)’.

This falls within the scope of the product’s designated orphan indication, which is: ‘5q spinal muscular atrophy’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2012. 5q spinal muscular atrophy remains a condition that is long-term debilitating and life threatening because it causes muscle wasting, breathing problems and paralysis that worsen over time.

Prevalence of the condition

The sponsor provided an updated calculation of the prevalence of 5q spinal muscular atrophy based on available epidemiological studies.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of 5q spinal muscular atrophy 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 still estimated to be less than 0.4 people in 10,000. This is equivalent to a total of fewer than 21,000 people in the EU.

Existence of other methods of treatment

The COMP noted that, at the time of the review of the orphan designation, no treatments were authorised in the EU for patients affected by this condition.

Conclusions

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

Related information

Sponsor’s contact details

Biogen Idec Ltd
Innovation House
70 Norden Road
Maidenhead
Berkshire SL6 4AY
United Kingdom
Tel. +44 (0)1628 501 000
Fax +44 (0)1628 501 010
E-mail: ukreception@biogenidec.com

Patients' organisations:

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.