Santhera to discontinue Phase 3 SIDEROS study

Santhera to discontinue Phase 3 SIDEROS study and development of Puldysa® in Duchenne Muscular Dystrophy (DMD) and focus on vamorolone.

Original Press Release > Pratteln, Switzerland, October 6, 2020

Santhera Pharmaceuticals announces the discontinuation of its Phase 3 SIDEROS study with Puldysa® (idebenone) in patients with Duchenne muscular dystrophy (DMD) who are in respiratory decline and receive concomitant glucocorticoid treatment. Data from an interim analysis conducted by the independent Data and Safety Monitoring Board (DSMB) concluded that the study was unlikely to meet its primary endpoint. Consequently, Santhera will discontinue the study, withdraw the European marketing authorization application and end the global development program for Puldysa. The Company intends to initiate a restructuring plan to retain key functions for bringing DMD drug candidate vamorolone to patients and execute on its other pipeline programs.

Based on the now completed interim analysis tested for efficacy, the DSMB has recommended the SIDEROS study be discontinued due to futility. The interim analysis was based on the study’s primary endpoint, the change of forced vital capacity % predicted (FVC%p) from baseline to 18 months of treatment. The outcome revealed that the probability of reaching the primary endpoint at the end of the study is too small to merit the study’s continuation. There were no safety concerns noted by the DSMB.

Santhera will stop the SIDEROS trial.

Santhera will stop the SIDEROS trial (including extension), and participants who are enrolled in the study will discontinue study medication and complete the study’s follow-up evaluations. Furthermore, following up on the recommendation from the DSMB, Santhera will discuss the impact of ending the SIDEROS study on ongoing expanded access programs with the corresponding regulatory bodies.


Dario Eklund, Chief Executive Officer of Santhera “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. 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.”


In connection with this decision, Santhera intends to start a restructuring process, aligning its operations to focus on progressing vamorolone for DMD, lonodelestat for cystic fibrosis and other lung diseases discovery-stage gene therapy approach for congenital muscular dystrophy.


SIDEROS was a clinical trial in DMD, 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 trial’s primary endpoint estimates the treatment difference in FVC%p (forced vital capacity % predicted). Read more about Idebenone.

About Santhera

Santhera Pharmaceuticals is a Swiss specialty pharmaceutical company focused on developing and commercializing innovative medicines for rare neuromuscular and pulmonary diseases with a high unmet medical need. Santhera has an exclusive license for all indications worldwide to vamorolone, a first-in-class anti-inflammatory drug candidate with a novel mode of action, currently investigated in a pivotal study in patients with DMD as an alternative to standard corticosteroids. The clinical-stage pipeline also includes lonodelestat (POL6014) to treat cystic fibrosis (CF) and other neutrophilic pulmonary diseases and omigapil and an exploratory gene therapy approach targeting congenital muscular dystrophies. Santhera out-licensed ex-North American rights to its first approved product, Raxone® (idebenone), to treat Leber’s hereditary optic neuropathy (LHON) to Chiesi Group. For further information, please visit  La Force DMD Blog /worldwide rights of vamorolone for DMD


Pfizer receives FDA fast track designation for DMD gene therapy

Pfizer receives FDA fast track designation for Duchenne muscular dystrophy (DMD) investigational gene therapy.

Official press release > NEW YORK–(BUSINESS WIRE)

Pfizer Inc. announced that its investigational gene therapy candidate (PF-06939926) being developed to treat Duchenne muscular dystrophy (DMD) received Fast Track designation from the U.S. Food and Drug Administration (FDA). PF-06939926 is currently being evaluated to determine the safety and efficacy of this gene therapy in boys with DMD.

Fast Track is a process designed to facilitate the development and expedite the review of new drugs that are intended to treat or prevent severe conditions that have the potential to address an unmet medical need. This designation was granted based on data from the Phase 1b study that indicated that the intravenous administration of PF-06939926 was well-tolerated during the infusion period, and dystrophin expression levels were sustained over 12 months.


Brenda Cooperstone, MD, Chief Development Officer, Rare Disease, Pfizer Global Product Development – “The FDA’s decision to grant our investigational gene therapy PF-06939926 Fast Track designation underscores the urgency to address a significant unmet treatment need for Duchenne muscular dystrophy. DMD is a devasting condition and patients, and their parents, are waiting desperately for treatment options. We are working to advance our planned Phase 3 program as quickly as possible.”


DMD is a devastating and life-threatening X-linked disease caused by mutations in the gene encoding dystrophin, which is needed for proper muscle membrane stability and function. Patients present with muscle degeneration that progressively worsens with age to the extent that they require wheelchair assistance when they are in their early teens, and unfortunately, usually succumb to their disease by the time they are in their late twenties. It is estimated that there are ~10-12,000 individuals affected with DMD in the U.S.


About PF-06939926

PF-06939926 is an investigational, recombinant adeno-associated virus serotype 9 (rAAV9) capsid carrying a shortened version of the human dystrophin gene (mini-dystrophin) under the control of a human muscle specific promotor. The rAAV9 capsid was chosen as the delivery vector because of its potential to target muscle tissue. Pfizer initiated the Phase 1b multi-center, open-label, non-randomized, ascending dose study of a single intravenous infusion of PF-06939926 in 2018. The goal of the study is to assess the safety and tolerability of this investigational gene therapy. Other objectives of the clinical study include measurement of dystrophin expression and distribution and assessments of muscle strength, quality and function.

Data from the Phase 1b DMD gene therapy program, including data from an additional nine boys, who were all administered the high dose of the investigational therapy. A total of 15 boys have now been treated with the high dose and 18 boys have been treated overall. > Sources<

  • No Serious Adverse Events (SAE) were observed among the nine additional boys who were treated using a modified immunomodulatory regimen and monitoring regimen. The prophylactic steroid treatment was also changed from 1 mg/kg to an intermediate dose of 2mg/kg.
  • Three of the nine boys were dosed with gene therapy product that was manufactured using the commercial manufacturing process developed at Pfizer’s facility in Sanford, North Carolina.
  • Based on these data, the Company plans to initiate the pivotal study in the next several weeks, with the plan to perform an interim analysis of the clinical data in 2022.

About Pfizer Rare Disease

Rare disease includes some of the most serious of all illnesses and impacts millions of patients worldwide, representing an opportunity to apply their knowledge and expertise to help make a significant impact on addressing unmet medical needs. The Pfizer focus on rare disease builds on more than two decades of experience, a dedicated research unit focusing on rare disease, and a global portfolio of multiple medicines within several disease areas of focus, including rare hematologic, neurologic, cardiac and inherited metabolic disorders.

Pfizer Rare Disease combines pioneering science and a deep understanding of how diseases work with insights from innovative strategic collaborations with academic researchers, patients, and other companies to deliver transformative treatments and solutions. Pfizer innovates every day, leveraging its global footprint to accelerate the development and delivery of groundbreaking medicines and the hope of cures.

Click here to learn more about their Rare Disease portfolio and how Pfizer empowers patients, engage communities in their clinical development programs, and support programs that heighten disease awareness.

Interesting links

La Force DMD talks with Dr. Jeffrey Chamberlain, a geneticist at the University of Washington, Seattle, about adenovirus-associated (AAV) micro-dystrophin gene replacement therapy.

La Force DMD / Press release from Pfizer about gene therapy