Santhera Pharmaceuticals intends to file for a conditional marketing authorization with the European Medicines Agency (EMA) for idebenone — to be marketed as Puldysa — as a treatment for respiratory dysfunction in Duchenne muscular dystrophy (DMD).
As it continues to gather data on the therapy, the company is recruiting participants for a Phase 3 clinical trial (NCT03603288), called SIDEROS-E. It is aimed at assessing the long-term safety and efficacy of idebenone in DMD patients who completed the Phase 3 SIDEROS study (NCT02814019).
Santhera has gathered clinical data from four clinical trials, including the pivotal Phase 3 DELOS trial and the recently completed SYROS study, which showed that long-term treatment with idebenone slows the loss of respiratory function in DMD patients for up to six years.
Puldysa will be indicated to treat respiratory dysfunction in patients with DMD who are not using glucocorticoids. Glucocorticoids currently are the only available treatment that can slow the decline in muscle strength and function in DMD, regardless of the disease-causing mutation. However, its efficacy is limited and is linked to side effects.
The Phase 3 DELOS (NCT01027884) trial recruited 64 patients (ages 10–18) who were randomly assigned to receive either idebenone (900 mg/day) or a placebo three times a day with meals for 52 weeks.
Results showed that idebenone reduced the loss of respiratory function, delaying the need for assisted ventilation by three years.
In the SYROS trial, investigators collected long-term, retrospective real-world data from the 18 patients who completed the DELOS study and continued idebenone treatment (same dose) for about 4.2 years (ranging from 2.4–6.1 years).
The trial measured patients’ respiratory function for up to six years and compared it with the period before idebenone treatment.
In line with DELOS’ findings, the results showed that idebenone reduced respiratory function decline by 50 percent, measured by the predicted forced vital capacity of each patient.
Forced vital capacity refers to the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible; doctors can predict a normal value for it based on a patient’s age, height, race, and gender.
Most importantly, idebenone’s therapeutic effects were maintained for up to six years. The therapy was also associated with a lower rate of lung-related adverse events and hospital admissions.
Inspiratory and expiratory respiratory function was conserved for a longer period while on idebenone, compared with patients’ clinical status before DELOS.
Moreover, in both trials, treatment with idebenone reduced the risk of hospitalizations due to impaired respiration and the rate of bronchopulmonary adverse events.
“Our team has worked hard to assemble new data which substantially strengthen our regulatory dossier for Puldysa as a potential treatment for DMD,” Kristina Sjöblom Nygren, MD, chief medical officer and head of development at Santhera, said in a press release.
“The continued dialogue with regulators and clinical experts in DMD has provided the necessary guidance which enabled us to close earlier data gaps by bridging clinical trial results to tangible and highly relevant patient benefits,” Nygren added.
Idebenone is a synthetic analog of ubiquinone, a key antioxidant that also plays a role in the cellular production of energy.
The chemical compound allows muscle cells to maintain their cellular energy supply, which has been compromised by a disease-specific lack of dystrophin.
Idebenone, marketed under the brand name Raxone, is already approved in Europe to treat visual impairment in adults and adolescents ages 12 and older with Leber hereditary optic neuropathy (LHON). For treatment in DMD patients, it will be branded as Puldysa to differentiate between the two indications.
“The choice for a conditional marketing authorization pathway was acknowledged by regulators and we are in final preparations to submit the filing dossier,” said Thomas Meier, PhD, CEO of Santhera.
“The regulatory path of a conditional marketing authorization requires us to submit a full dossier with a new tradename, Puldysa, to distinguish this product from Raxone which was previously approved as treatment for patients with Leber’s hereditary optic neuropathy,” Meier added.
Conditional marketing authorization may be granted to medicines whose benefit of immediate availability outweighs the risk of having less comprehensive data. This authorization is valid for one year, but can be renewed annually, and the applicant is expected to outline a timeline for delivering additional data.