Santhera said in a press release that it plans to appeal the Committee for Medicinal Products for Human Use’s decision, which covers Raxone in DMD patients not being treated with glucocorticoids. The committee, known as CHMP, is the regulatory arm of the European Medicines Agency, or EMA.
The opinion, which was in response to a Type II extension application that Santhera filed, may have taken the company by surprise. Santhera had offered an upbeat picture of ongoing talks with CHMP about the application as recently as May.
Raxone is already approved in the European Union as a treatment for Leber’s hereditary optic neuropathy, or LHON. The extension sought to expand its approval to Duchenne patients whose respiratory function is declining and who are not using glucocorticoids, or steroids.
Santhera supported the application with results from the Phase 2 DELPHI clinical trial (NCT00654784) and the Phase 3 DELOS study (NCT01027884). DELOS, a 52-week placebo-controlled, randomized study of 64 DMD patients, met its primary objective of slowing patients’ decline in respiratory function. The yardstick researchers used was changes in treated patients’ Peak Expiratory Flow from the study’s start.
CHMP expressed doubts that the DELOS trial results provided sufficient evidence of effectiveness to support Raxone’s approval for Duchenne patients.
“We are surprised and disappointed by the opinion of the CHMP,” said Thomas Meier, Santera’s chief executive officer. “Data from the phase III DELOS trial demonstrated statistically significant and clinically relevant evidence that Raxone slows the decline of respiratory function, and reduces the risk of bronchopulmonary complications and hospitalization, in patients with DMD not using glucocorticoids.
“These patients in the respiratory decline stage currently have no treatment options, and because we are confident that they could benefit from treatment with Raxone, we plan to appeal this opinion and seek re-examination,” he added.
The U.S. Food and Drug Administration has not approved idebenone for any disease. It has designated it an orphan drug as a potential treatment for both LOHN and Duchenne MD, however.
The FDA declined Santera’s request for accelerated approval of idebenone as a DMD treatment in July 2016, also on the grounds that the DELOS trial results were insufficient. It requested that any application for approval include data from an ongoing Phase 3 trial, SIDEROS (NCT02814019), which is assessing idebenone in DMD patients using glucocorticoids.
Results of the SIDEROS trial are not expected until 2019, the Muscular Dystrophy Association reported at the time, noting that an FDA review could be pushed back to 2020.
Marketing approval of a potential treatment in Europe is made by the European Commission, but its decision is usually in agreement with the opinion expressed by the EMA and its scientific arm, CHMP.