Drugs Xagena
On 21 March 2013, Santhera Pharmaceuticals ( Deutschland ) GmbH officially notified the Committee for Medicinal Products for Human Use ( CHMP ) that it wishes to withdraw its application for a marketing authorisation for Raxone, for the treatment of Leber’s hereditary optic neuropathy ( LHON ).
Raxone is a medicine that contains the active substance Idebenone. It was to be available as 150 mg tablets.
Raxone was expected to be used for the treatment of LHON, which is an inherited disease characterised by progressive loss of sight.
Raxone was designated an orphan medicine on 15 February 2007 for the treatment of LHON.
The active substance in Raxone, Idebenone, acts on structures inside cells known as mitochondria, which produce the energy necessary for cells to function. Patients affected by LHON have mutations in the genetic material of mitochondria. This means that mitochondria do not work properly to generate energy, and produce toxic forms of oxygen ( free radicals ) that damage nerve cells in the eye that are needed for vision. The way Idebenone works in LHON is not fully understood but it is thought to reduce the formation of free radicals and to help improve production of energy, thereby preventing the cellular damage and the loss of sight seen in LHON.
The company presented the results from one main study with Raxone involving 85 patients with LHON whose symptoms started in the previous five years. In the study, patients received Raxone or placebo for six months. The main measure of effectiveness was the change in vision after six months of treatment measured using a standard eye test with a letter chart.
The evaluation had finished and the CHMP had given a negative opinion. The company had requested a re-examination of the negative opinion, but withdrew before this re-examination had started.
Based on the review of the data, at the time of the withdrawal, the CHMP had given a negative opinion recommending that the marketing authorisation be refused for Raxone for the treatment of Leber’s hereditary optic neuropathy.
At the time of the negative opinion, the CHMP was concerned that in patients with LHON whose symptoms started in the previous five years, taking Raxone for six months did not lead to a significant improvement in vision compared with placebo ( patients taking Raxone were able to distinguish three more letters on the letter chart compared with patients taking placebo ). The CHMP did not consider this benefit to be significant.
Based on the same study, the company later proposed to restrict the use of Raxone to patients with LHON whose symptoms started in the previous year. These patients showed an improvement of 17 letters on the letter chart compared with placebo. However, the CHMP concluded that the new sub-group of patients proposed for treatment was not well represented in the study ( 28 patients ) and the reliability of the results is questionable. Given the small size of this sub-group, the CHMP considered that a spontaneous improvement could not be ruled out.
In addition, the CHMP considered that the data supporting the mode of action for idebenone in LHON are not sufficient. Therefore, at the time of the withdrawal, the CHMP was of the opinion that the benefits of Raxone did not outweigh its risks. ( Xagena )
Source: European Medicines Agency, 2013
XagenaMedicine_2013
