Santhera Pharmaceuticals (SIX: SANN) announces full recruitment of its Phase 3 SIDEROS study with idebenone in Duchenne muscular dystrophy (DMD). The sample-size and variability re-assessment performed according to study protocol demonstrated that with the currently enrolled patients the study has a very high power (>99%). Given the strong powering of SIDEROS, the Company is now assessing the potential of conducting an interim analysis to test for overwhelming efficacy with a view of completing the trial early.
With patient recruitment into the 18-month international SIDEROS trial in its final stages, Santhera performed the planned sample size and variability re-assessment in accordance with the study protocol to confirm adequate study power. This blinded analysis showed that variability is lower than anticipated per protocol and, with the current number of enrolled patients, the SIDEROS study has a very high power of over 99% to detect a treatment difference. On this basis, Santhera has taken the decision to complete enrollment into the SIDEROS trial. At present, approximately half of the recruited patients in SIDEROS have completed 18 months of treatment and about two thirds of patients have completed 12 months of treatment.
Owing to the decision to complete enrollment of this advanced study, its very high power as well as the urgent unmet medical need, Santhera is assessing the potential of conducting an interim analysis to test for overwhelming efficacy with a view of completing the trial early. Such an interim analysis would be performed by the independent Data and Safety Monitoring Board (DSMB) to preserve the integrity of the study. If overwhelming efficacy is not established in the interim analysis, the study could continue as planned with the currently enrolled patients and the corresponding high power. However, if overwhelming efficacy is demonstrated, it would be considered unethical to continue with the blinded study and the Company would decide to end the study later this year. This would result in acceleration of corresponding regulatory filings by approximately one year both in Europe and the US.
”Santhera is the only company that has dedicated its clinical development program towards finding a treatment to preserve respiratory function in DMD. The large Phase 3 SIDEROS study was designed to confirm the efficacy of idebenone in patients with respiratory function decline who are concurrently taking glucocorticoids,” said Gunnar Buyse, MD, PhD, Professor of Child Neurology at the University Hospitals Leuven (Belgium), SIDEROS Principal Investigator and Lead Investigator for Europe. “We are truly excited that SIDEROS has completed recruitment and is on track to generate a comprehensive dataset in an area of such high unmet need.”
“There are currently no approved treatments to slow the rate of respiratory function decline leading to respiratory failure, which remains a leading cause of premature death in young men at the advanced stages of DMD,” commented Oscar Henry Mayer, MD, Medical Director of the Pulmonary Function Testing Laboratory at the Children’s Hospital of Philadelphia and Lead Investigator for US. “By slowing the rate of respiratory function decline, we open the possibility to delaying the time to chronic respiratory failure and the need to assisted ventilation and reducing the risk of other life-threatening respiratory complications.”
“We are delighted to have reached such an important milestone and wish to express our sincere thanks to patients and families, caregivers, physicians and study personnel for their support and commitment,” added Kristina Sjöblom Nygren, MD, Chief Medical Officer and Head of Development of Santhera.
SIDEROS, the largest currently ongoing clinical trial in DMD, is a double-blind randomized placebo-controlled Phase 3 study evaluating the efficacy of idebenone in delaying the loss of respiratory function in patients with DMD. Patients on any stable glucocorticoid treatment scheme and irrespective of the underlying dystrophin mutation or ambulatory status were randomized to receive oral idebenone (900 mg/day three times a day) or placebo for 18 months. The primary endpoint of the trial estimates the treatment difference in FVC%p (forced vital capacity % predicted). Patients completing the trial are offered the opportunity to enroll in an open label extension study where all patients receive idebenone. The study is currently conducted in 62 sites in the United States, Europe and Israel. Further information is available at ClinicalTrials.gov NCT#02814019.