What is Opgenra?
Opgenra is a medicine that contains the active substance eptotermin alfa supplied in two vials, one containing eptotermin alfa and the other containing a substance called carmellose. The two powders are used to prepare a "suspension" (liquid containing solid particles inside it) of a pasty consistency to be implanted inside the body.
What is Opgenra used for?
Opgenra is used in adults with spondylolisthesis, a disease in which a lumbar vertebra (one of the bones of the lower part of the spine) has slipped forward and is no longer aligned with the underlying vertebra. This condition can cause pain, instability and problems due to pressure on the nerves including tingling, numbness, weakness and difficulty in controlling some muscles. Spondylolisthesis can be treated surgically to melt (join) the overlying vertebra and the one below the slip point.
Opgenra is used exclusively in patients who have previously undergone unsuccessful autologous grafting (bone graft taken from another bone of the same patient, usually the hip) or in patients who cannot undergo this surgery.
The medicine can only be obtained with a prescription.
How is Opgenra used?
Opgenra should only be used by a suitably qualified surgeon. During the surgery, the surgeon applies Opgenra directly along both sides of the two vertebrae to promote the formation of new bone and to allow fusion of the vertebrae.
How does Opgenra work?
The active substance in Opgenra, eptotermin alfa, acts on the bone. It is a replica of the osteogenic protein 1, also called bone morphogenic protein 7 (BMP-7), a protein produced naturally by the body and which contributes to the formation of new bone tissue. Once implanted, heptotermin alfa stimulates the formation of new bone, helping to fuse the two vertebrae in the spondylolisthesis operated patients.
Eptotermin alfa is produced with the so-called 'recombinant DNA technology', that is by inserting a gene (DNA) into the cells which thus become able to produce eptotermin alfa. Substitutive eptotermin alfa acts in the same way as naturally produced BMP-7.
Eptotermin alfa has been authorized by the European Union (EU) since May 2001 in the medicinal product Osigraft, which is used to repair tibia fractures.
How has Opgenra been studied?
The effects of Opgenra were first tested in experimental models before being studied in humans. The company also used some of the data used at the time to obtain authorization from Osigraft.
Opgenra was the subject of a main study involving 336 patients who had to undergo spinal fusion spondylolisthesis surgery. All patients were eligible for autologous grafting. The study compared the intervention performed with Opgenra with the intervention performed with an autologous graft. The main measure of effectiveness was the number of patients whose treatment was successful after two years. Treatment was considered "successful" if bone tissue was visible between the two affected vertebrae on the X-ray and if the patient showed an improvement in disability, without the need for further treatment of the spine, no serious side effects and no worsening of symptoms caused by pressure on the nerves.
The company also presented evidence contained in the scientific literature published in patients treated in the United States (USA), where the medicine has been approved for spinal fusion since 2004.
What benefit has Opgenra shown during the studies?
In the main study, Opgenra was not as effective as autologous grafting in patients eligible for this last treatment. After two years treatment with Opgenra was successful in 39% of patients, compared with 49% of patients with autologous grafting.
Despite the lower efficacy, sufficient evidence emerged from the study and from the published literature in favor of the use of Opgenra in patients in whom the autologous graft was not successful or in patients unsuitable for this intervention. In addition, Opgenra has some advantages over autologous grafting, including shorter operative times, less blood loss and less pain.
What is the risk associated with Opgenra?
The most common side effects of Opgenra (seen in between 1 and 10 patients in 100) are heterotopic ossification (formation of bone outside the fusion area) and pseudoarthrosis (lack of spinal fusion). There are also undesirable effects seen in 1-10 patients out of 100 following the spinal surgery itself, which include infection after the operation, dehiscence (opening) of the wound, oozing and erythema (redness of the skin). For the full list of all side effects reported with Opgenra, see the Package Leaflet.
Opgenra should not be used in patients who may be hypersensitive to heptotermin alfa or any of the other components. It must also not be used in the following groups:
- patients with autoimmune disease (disease caused by the body's immune system attacking normal tissues);
- patients with active infection on the operated site or subject to repeated infections;
- patients with insufficient cutaneous coverage or blood supply at the operation site;
- patients previously treated with BMP-containing drugs;
- patients with cancer or undergoing cancer treatment;
- patients with bone still being trained, such as children and adolescents.
Why has Opgenra been approved?
The Committee for Medicinal Products for Human Use (CHMP) decided that Opgenra's benefits are greater than its risks for posterolateral lumbar spinal fusion in adult patients with spondylolisthesis in case of previous autologous graft failure or contraindication to such treatment. The committee recommended that Opgenra be given marketing authorization.
What measures are being taken to ensure the safe use of Opgenra?
The company that makes Opgenra is committed to providing an information kit and self-instruction DVD to surgeons in various Member States, including information on the safety of Opgenra and a reminder for the preparation and use of the medicine during the operation. The company also undertook to submit to the CHMP projects for long-term studies that will assess the safety and efficacy of the medicine and the way it is used in real conditions.
More information on Opgenra:
On February 19, 2009, the European Commission issued a marketing authorization valid for Opgenra to Howmedica International S. de RL, valid throughout the European Union.
For the full EPAR of Opgenra, click here.
Last update of this summary: 11-2008.
