• Email
  • Help

Orphan designation

On 14 December 2015, orphan designation (EU/3/15/1595) was granted by the European Commission to Coté Orphan Consulting UK Limited, United Kingdom, for live attenuated Listeria monocytogenes bioengineered with a chimeric human epidermal growth factor receptor 2 fused to a truncated form of the Lm protein listeriolysin O (also known as ADXS31-164) for the treatment of osteosarcoma.

The sponsorship was transferred to Quintiles Ireland Limited, Ireland, in March 2018.

In May 2018 the sponsor, Quintiles Ireland Limited changed name to IQVIA RDS Ireland Limited.

What is osteosarcoma?

Osteosarcoma is a type of cancer that affects bone-forming cells. It usually affects the growing bone and occurs mainly in teenagers and young adults. Although it can develop in any bone in the body, it most often starts in the bones around the knee joint in the area of bone with the fastest growth. The most common symptom is pain, which may be worse at night. Symptoms also depend on where the cancer has spread to. The most common site of spread for this cancer is the lungs.

Osteosarcoma is a long-term debilitating and life-threatening disease that may require patients to undergo limb amputation and is associated with poor long-term survival.

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

At the time of designation, osteosarcoma affected approximately 2.8 in 10,000 people in the European Union (EU). This was equivalent to a total of around 144,000 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).

*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. This represents a population of 512,900,000 (Eurostat 2015).


What treatments are available?

At the time of designation, the main treatments for osteosarcoma were surgery and chemotherapy (medicines to treat cancer). The goal of surgery was to remove cancerous bone while preserving as much skeletal function as possible. Chemotherapy was normally used to shrink the tumour before surgery and also after surgery to stop any remaining cancer cells from spreading. A number of chemotherapy medicines, including cisplatin, were authorised in the EU for this condition.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit to patients with osteosarcoma because early studies in experimental models showed improved survival when the cancer had spread to other parts of the body. 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?

The medicine works by stimulating the patient’s immune system, the body’s natural defences, so that it targets and destroys the cancer cells. It is made of live Listeria monocytogenes bacteria, which have been attenuated (weakened) so that they do not cause disease in humans. The bacteria have also been modified to produce large amounts of the ‘human epidermal growth factor receptor 2’ (HER2). HER2 is found at high levels on many types of cancer cells, including osteosarcoma cells. The HER2 on the bacteria has been attached to a protein called listeriolysin O, which helps it to stimulate the body’s immune system.

When the medicine is given, the patient’s immune system is expected to learn to treat HER2 as ‘foreign’. This is expected to stimulate an immune response against the osteosarcoma cells carrying HER2 on their surface, resulting in the immune system attacking and destroying the cancer cells.

What is the stage of development of this medicine?

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

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with osteosarcoma had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for osteosarcoma. Orphan designation of the medicine had been granted in the United States for osteosarcoma.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 November 2015 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>live attenuated Listeria monocytogenes bioengineered with a chimeric human epidermal growth factor receptor 2 fused to a truncated form of the Lm protein listeriolysin O</p>
Active substancelive attenuated Listeria monocytogenes bioengineered with a chimeric human epidermal growth factor receptor 2 fused to a truncated form of the Lm protein listeriolysin O
Medicine Name
Disease/conditionTreatment of osteosarcoma
Date of decision14/12/2015
Orphan decision numberEU/3/15/1595

Review of designation

Sponsor’s contact details

IQVIA RDS Ireland Limited
Estuary House
East Point Business Park
Dublin 3
Tel. +353 1819 5100

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.