Safety and Efficacy of Tamoxifen in Patients with Duchenne muscular dystrophy: open Label Extension of TAMDMD Trial

Safety and efficacy of tamoxifen in boys with Duchenne muscular dystrophy was assessed in the double-blind, randomised, placebo-controlled, multicenter phase 3 trial (TAMDMD), which was followed by an 48 weeks open label extension study. The aim of the open label extension study was to investigate if earlier initiation of tamoxifen could reduce the progression of the disease compared to delayed initiation of tamoxifen. Of the initial TAMDMD trial participants, 66 patients were enrolled in the open label extension (OLE). The objective was to investigate the efficacy of prolonged treatment with tamoxifen 20 mg daily, adjunct to corticosteroids, in individuals with DMD over 48 weeks. We aimed to analyse the sustained effect and the timing effect of tamoxifen in patients with DMD on the basis of a set of motor function tests. The sustained effect corresponds to the treatment effect seen in the tamoxifen treatment arm of the RCT phase of the trial being sustained after all patients got the treatment in the OLE phase. The timing effect addresses if patients with earlier tamoxifen initiation show more favourable disease trajectory than patients with delayed tamoxifen initiation. This study was registered with ClinicalTrials.gov (NCT03354039). Between May 28th 2019 and July 28th 2021, 66 patients in 10 study centres in seven European countries could be enrolled into the OLE phase. Of those, 32 had previously been treated with tamoxifen and 34 had been assigned to placebo. The efficacy outcome defined as the change in the motor function did not differ significantly between the early tamoxifen treatment group and the delayed tamoxifen treatment group. There was neither a sustained nor a timing effect of tamoxifen. Overall tamoxifen was well tolerated. No deaths or life-threatening serious adverse events occurred. The OLE phase of the TAMDMD trial showed that treatment with tamoxifen continued to be well tolerated overall; however, there was neither a sustained nor a timing effect of tamoxifen treatment in patients with DMD. We cannot provide statistical nor clinical evidence that prolonged treatment with tamoxifen is effective in delaying disease progression in DMD when used as an adjunct to corticosteroids.