The Orphan Drug Designation applies specifically to the use of AV0113 for the treatment of glioma, a type of brain tumour, which afflicts around one in 10.000 people in the EU. The term Orphan Disease refers to rare diseases which do not attract much interest in the way of research and development and thus for which there are no appropriate treatments available.
Activartis’ AV0113 Cancer Immune Therapy can basically be used to fight every type of cancer. The therapeutic technology is based on a patented procedure in which a cancer patient’s immune system is primed to fight the tumour and eventually control its growth. This is based on the use of Dendritic Cells, the key regulatory elements of the immune system, that are just as the tumour tissue derived from the patient.
Active cancer immune therapy based on Dendritic Cells
AV0113 activates the patient’s immune system, with tumour cells being identified on the basis of their antigens and destroyed. The therapy makes use of elements and mechanisms of the immune system and gets to work where these fail. As tumour cells are the body’s own tissue, the immune system normally doesn’t identify them as dangerous. Activartis’ AV0113 Cancer Immune Therapy “tricks” Dendritic Cells, and consequently a cancer patient’s immune system, into doing the right thing, i.e. to perceive the tumour as a threat and to trigger adequate defence mechanisms.
The Dendritic Cells are charged with tumour-derived antigens, determinants that distinguish a tumour cell from a normal cell. These antigens are processed by the Dendritic Cell and shuttled to the cell surface in order to present them to T-cells. This, however, is not sufficient to prime an immune response against the tumour antigens. The “trick” referred to above is contacting Dendritic Cells with a microbial danger signal. Certain molecules, that are present in microorganisms but not in higher organisms signal the Dendritic Cell the presence of a microorganism in its surroundings and hence danger to the organism.
As tumour cells originate from a cancer patient’s normal cells, they do not provide such danger molecules for recognition by the Dendritic Cell. The critical and unique part of Activartis’ AV0113 technology is exposing tumour antigen-charged Dendritic Cells to one of these danger molecules: Lipopolysaccharides, the bacterial endotoxins. This causes the Dendritic Cell to assume a potently immune stimulatory and pro-inflammatory mode of action. Upon returning these Dendritic Cells to the patient they activate tumour-specific T-cells, most importantly the so-called Cytotoxic T-cells, which become enabled to recognise and destroy tumour cells.
EMA: First proof of efficacy expected
In order to award an orphan drug designation, the EMA requires preliminary indications that the medicine concerned may be effective – but yet not any definitive proof. Activartis has now been able to provide such indications in the case of patients with a particularly aggressive type of glioma, Glioblastoma multiforme. Every year about 50.000 people around the world are diagnosed with this aggressive type of brain tumour. Patients afflicted by Glioblastoma do not live much longer than one year on average. More than 90% of patients die within a five-year period. The classic forms of cancer therapy – surgery, irradiation and chemotherapy – only extend the lives of patients by a few months.
The director of the team that developed this new form of Cancer Immune Therapy, Thomas Felzmann, who is now CEO of Activartis, says: “Acquiring orphan drug designation is an important milestone for us and a strong signal to others. We are convinced that this approach has great potential and now an independent party, the European Medicines Agency, has confirmed this. However, it will still take another year or so before robust evidence for a benefit of AV0113 for patient’s suffering from Glioblastoma will become available.”
The majority of neuro-surgical/neuro-oncological clinics in Austria currently participate in a randomised phase II study, GBM-Vax, designed to deliver evidence for AV0113’s efficacy. GBM-Vax has recruited close to 100 Glioblastoma patients. Now we have to wait and see whether patients survive longer when treated with the AV0113 Cancer Immune Therapy.
Keyword: Orphan Drug Designation
Due to their rarity biomedical research and development often neglects rare diseases. Consequently, such diseases are referred to as orphans. For Orphan Diseases the European and US medical authorities, EMA and FDA, award an Orphan Drug Designation for medicaments that may be used for treating one of these very rare diseases. Before an active substance is designated as Orphan Drug, medical authorities determine if the developer of the medicine can demonstrate that the drug may have an effect, in addition to ascertaining if the disease in question is in fact rare. Advantages conferred by an Orphan Drug Designation include an accelerated approval procedure and market exclusivity in Europe for ten years from the date of approval and seven years in the USA. As a result, Orphan Drug Designation promotes the development of medication for people who are afflicted by rare, life-threatening diseases.
Activartis is a biotech company based in Vienna. The majority owner is the Austrian pharmaceutical company AOP Orphan Pharmaceuticals AG, which specialises in the development and distribution of pharmaceuticals for Orphan Diseases. Activartis was founded in 2003 as a spin-off of the St. Anna Children’s Cancer Research Institute, Vienna, Austria. Activartis is currently in phase II of clinical trials for a new kind of Cancer Immune Therapy. The therapeutic technology combines a completely new, patented approach, AV0113, that uses a bacterial danger signal together with the patient’s tumour antigens, with the concept of Dendritic Cells already marketed. The aim is to enable the immune system to gain control of the cancer.