Phase 3 Trial of Puldysa Stopped for Lack of Efficacy in Duchenne Patients

Phase 3 Trial of Puldysa Stopped for Lack of Efficacy in Duchenne Patients
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Santhera Pharmaceuticals has decided to stop SIDEROS, its Phase 3 trial assessing the effectiveness of Puldysa (idebenone) at delaying respiratory decline in patients with Duchenne muscular dystrophy (DMD) on a stable glucocorticoid dose.

An interim data analysis of the study (NCT02814019), which was fully enrolled, determined that SIDEROS was unlikely to achieve its primary goal of slower lung function decline — as measured by changes in forced vital capacity percent predicted — over 18 months of treatment.

This efficacy analysis was conducted by the trial’s independent Data and Safety Monitoring Board. The board found no safety concerns regarding treatment.

“We would like to thank the patients and the families, as well as investigators and medical professionals, who participated in the SIDEROS study. Without their contributions we would not be able to advance DMD research,” Dario Eklund, CEO of Santhera, said in a press release.

Based on these futility findings, Santhera decided to halt both SIDEROS and its open-label extension study (NCT03603288), and to suspend Puldysa’s development program. The company also withdrew its application to the European Medicines Agency, requesting Puldysa’s approval to treat respiratory dysfunction in people with DMD.

All enrolled patients will stop taking Puldysa, designed to aid breathing by improving mitochondrial function within cells, and will complete follow-up evaluations. In line with the board’s recommendations, Santhera will also meet with regulatory authorities to discuss the impact of suspending SIDEROS on current expanded access programs.

Santhera is now planning to focus on vamorolone (VBP15), an oral anti-inflammatory steroid treatment that aims to slow DMD progression with fewer side effects than corticosteroids — the current standard therapy for children and adolescents with Duchenne. The company recently acquired worldwide rights to vamorolone from ReveraGen Biopharma, its original developer.

Recent data from a Phase 2 trial (NCT02760277) and its open-label extension study (NCT03038399) showed that vamorolone was able to improve motor outcomes in boys, ages 4–7, with DMD, while causing fewer side effects compared with conventional corticosteroids, such as prednisone and Emflaza (deflazacort).

Compared with published data on patients using corticosteroids, vamorolone did not stunt growth, and led to lesser weight gain, behavioral changes, and hirsutism (excessive hair growth).

A Phase 2b trial called VISION-DMD (VBP15-004, NCT03439670) is now assessing the safety and efficacy of vamorolone, at 2 or 6 mg/kg daily, compared with prednisone or a placebo for up to 48 weeks in 121 Duchenne boys, ages 4–7, who are able to walk independently.

The company anticipates announcing top-line data from VISION-DMD, which recently completed enrollment, next year. 

“While this is obviously not the outcome we expected, all our efforts in DMD will now be focused on progressing the promising drug candidate vamorolone which we recently licensed from ReveraGen to its next inflection point, the readout of 6-month topline data from the pivotal VISION-DMD study planned for the second quarter of 2021,” Eklund said.

Santhera is also focused on developing lonodelestat to treat cystic fibrosis and other lung disorders, and developing new gene therapies for congenital muscular dystrophy.

Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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