Today, we are disappointed to learn that Santhera announced its decision to discontinue development of its Phase 3 SIDEROS study with Puldysa® (idebenone) in Duchenne. 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.

PPMD connected with Santhera today on the interim analysis results which found no difference in progression between the treatment and placebo groups in 197 trial participants who were included in the interim analysis. Santhera has committed to performing additional analysis in the coming weeks to fully understand the data. The company also remains committed to progressing vamorolone which was 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.

PPMD and World Duchenne Organization are working together with Santhera to plan a webinar with the global community to answer questions and to discuss the results and we will provide those details as soon as they are available.

We are grateful to all the families who have participated in clinical trials with idebenone, and to the Santhera team for their work to advance therapy development in non-ambulatory people with Duchenne. The failure of a trial is always difficult for our community, but we remain hopeful that the forthcoming data from this trial will inform other potential treatments and that these experiences will lead us to the day that we end Duchenne.

Read Santhera’s letter to the Duchenne community:

October 6, 2020

SIDEROS trial interim analysis – update from Santhera

Dear Duchenne community,

Since 2016, Santhera has been conducting one of the largest clinical trials in Duchenne muscular dystrophy – the SIDEROS study. SIDEROS is a phase III double-blind, randomized, placebo-controlled study assessing the efficacy, safety and tolerability of idebenone in patients with Duchenne muscular dystrophy receiving glucocorticoids. We regret to inform the Duchenne community, that based on the results of the interim analysis and recommendation from the trial’s Data and Safety Monitoring Board (DSMB), the SIDEROS trial has been deemed futile. Based on the results of the interim analysis, we have made the difficult decision to discontinue SIDEROS and the development of idebenone in Duchenne muscular dystrophy. This update serves to address the details of this morning’s press release with the community.

What does futility mean and how was this determined? Futility means that the probability for SIDEROS to reach its primary endpoint in the planned final analysis has become so small that continuation of the study cannot be justified any more. No difference was seen between the treatment and placebo groups in 197 trial participants who were included in the interim analysis. This was the basis for the DSMB recommendation.

What does this mean for the community?

Santhera has endorsed the DSMB recommendation and will discontinue the SIDEROS study. As a consequence, the development of idebenone in DMD will not be continued further, including SIDEROS-Extension and expanded access programs. Participating patients are asked to stop taking idebenone treatment immediately. Study sites will be in contact with study participants to schedule a final visit four weeks after stopping the investigational treatment. All study participants who have questions about the next steps should reach out to their clinical study site. Santhera will be in close communication with the study sites and investigators in the coming days.

It’s important to note that the DSMB has been reviewing the safety data throughout the conduct of the study and has not detected any new safety concerns.

Why did we conduct an interim analysis?

An interim analysis in a trial is an analysis of data that is conducted before data collection has been completed. In May, Santhera determined that enough of the participants had completed the study, the power of the study was high, and the variability in the primary endpoint was lower than expected. By conducting the interim analysis and stopping the study for futility, this ensures that study participants are not exposed to a treatment that is unlikely to be of clinical benefit or exposed to placebo for longer than is necessary.

Why is this being announced in a press release?

Pharmaceutical and biotechnology companies that are traded publicly are governed by strict regulations that dictate how companies release information that may have any impact on the value of the company or stock prices. This includes the release of clinical trial results. Therefore, the interim analysis results must be released via a press release as soon as possible after the DSMB recommendation has been made. Federal guidelines do not allow us to notify the study participants first.

While this is not the news that we hoped to share with the Duchenne community, Santhera’s team will fully analyze the study data to better understand the results of the interim analysis and will share additional insights with the Duchenne community via the patient advocacy groups. Santhera aims to continue data contributions to C-Path’s Duchenne Regulatory Science Consortium to help with their efforts to design more efficient trials using disease modeling expertise.

In closing, we would like to take this moment to express our deep appreciation to the participants in the SIDEROS study and all of the families that support them. Your commitment to the study, even in the midst of a global pandemic, has been nothing short of remarkable. We acknowledge that the discontinuation of a trial and development program is disappointing to the Duchenne community and we share your sentiment on these results. As a company, Santhera will remain committed to developing therapies for Duchenne muscular dystrophy. The Duchenne community is a model of resilience and we will keep working hard for your families.

With warm regards,

Dario Eklund
Chief Executive Officer

Jodi Wolff
Head of Patient Advocacy – U.S

Read the press release from Santhera:

Santhera to Discontinue Phase 3 SIDEROS Study and Development of Puldysa® in Duchenne Muscular Dystrophy (DMD) and Focus on Vamorolone

Pratteln, Switzerland, October 6, 2020 – Santhera Pharmaceuticals (SIX: SANN) 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. As a consequence, 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 for the business with a focus on retaining key functions for bringing DMD drug candidate vamorolone to patients and execute on its other pipeline programs.

Based on the now completed interim analysis which tested for efficacy, the DSMB has recommended the SIDEROS study be discontinued due to futility. The interim analysis was based on the primary endpoint of the study, 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 continuation of the study. There were no safety concerns noted by the DSMB.

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.

“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,” said Dario Eklund, Chief Executive Officer of Santhera. “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 and its discovery-stage gene therapy approach for congenital muscular dystrophy.

Click here to read the full press release.