Today Santhera announced that they have received a negative opinion on the Appeal for Authorization of Raxone® from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). While the news is disappointing, Santhera shares that they remain fully committed to addressing this unmet need in Duchenne and intends to collect further evidence to strengthen the clinical data package for Raxone in preparation of a refiling of a Marketing Authorization Application (MAA) in Europe. According to the company, this news will not impact Santhera’s US regulatory plans and they continue to prepare for a New Drug Application for Raxone.
Read today's Press Release and FAQ document from Santhera below.
Santhera Receives Negative CHMP Opinion on Appeal for Authorization of Raxone® in Duchenne Muscular Dystrophy
Liestal, Switzerland, January 26, 2018 - Santhera Pharmaceuticals (SIX: SANN) announces that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) maintained its negative opinion on the Type II extension application for Raxone® (idebenone) in Duchenne muscular dystrophy (DMD) following a re-examination procedure.
The CHMP concluded that an approval for Raxone in DMD, applied as a Type II variation of the existing marketing authorization, cannot be granted at the present time based on the current existing evidence. Although the positive outcome of the Phase III DELOS trial was acknowledged, the CHMP has invited Santhera to present additional data to further link the observed treatment effects on respiratory function outcomes to patient benefit.
Respiratory decline is one of the leading causes of death in patients with DMD and there is currently no approved treatment. Santhera remains fully committed to addressing this unmet need and is convinced of the treatment benefits of Raxone in DMD. Santhera intends to collect further evidence to strengthen the clinical data package for Raxone in preparation of a refiling of a Marketing Authorization Application (MAA) in Europe.
Santhera will continue working with regulatory authorities to bring this treatment option to patients as quickly as possible. The intended indication for Raxone is to slow the decline of respiratory function in patients with DMD who are currently not taking glucocorticoids. The indication would include patients in whom glucocorticoid treatment is no longer tolerated or is considered inadvisable.
"Data from the Phase III DELOS trial demonstrated statistically significant and clinically relevant evidence that Raxone slows the decline of respiratory function, and reduces the risk of bronchopulmonary complications and hospitalization in patients with DMD not using glucocorticoids. The CHMP acknowledged the unmet medical need in this patient population," said Thomas Meier, PhD, CEO of Santhera. "We are very grateful to the DMD community, patients, their caregivers and treating doctors, for their relentless support. Santhera remains fully committed to realizing the potential of Raxone in treating patients with DMD through its clinical trial program and disease awareness efforts in close cooperation with the medical community and patient organizations."
Jon Hastie, PhD and CEO of DMD Pathfinders, a user led organization of adults with Duchenne which provides peer support and advice for others living with the condition commented on today's news: "The news about Raxone being given a negative opinion is disappointing for individuals with DMD, particularly teenagers and adults experiencing respiratory decline. The need for assisted ventilation and the likelihood of chest infections and consequent emergency hospital admissions is a source of constant anxiety and has a significant burden on our lives. - There really is an urgent need to find a treatment to slow the decline in respiratory function in individuals who do not take steroids as there is no other treatment option available. I'm glad that Santhera will continue in their efforts to make Raxone available to patients."
"Across Europe about half of patients with DMD aged 10-20 years old are not able to take steroids or have stopped because of side effects. These patients are currently left with no treatment option to slow the progressive decline in their respiratory function. We will continue supporting Santhera in obtaining additional evidence required to have this medicine approved for this older group of DMD patients," said Thomas Voit, MD and Professor of pediatrics at the Great Ormond Street Hospital for Children and University College London (London, UK).
The MAA for Raxone in DMD was filed as a Type II Variation of the existing marketing authorization for Leber's hereditary optic neuropathy (LHON), and is based on data from Santhera's Phase II DELPHI study and the successful pivotal Phase III DELOS study, the latter in patients not taking concomitant glucocorticoids. These data demonstrated a statistically significant and clinically relevant outcome for Raxone in slowing the loss of respiratory function compared to placebo. The results of the Phase III DELOS study were published in several peer-reviewed journals: Buyse et al., The Lancet 2015, 385:1748-1757; McDonald et al., Neuromuscular Disorders 2016, 26:473-480; Buyse et al., Pediatric Pulmonology 2017, 52:580-515; Mayer et al., Journal of Neuromuscular Diseases 2017, 4:189-198; Meier et al., Neuromuscular Disorders 2017, 27:307-314.
In light of the CHMP's opinion, Santhera has withdrawn the corresponding regulatory application in Switzerland with the intention to refile at a later stage.
An investor conference call with Thomas Meier, PhD, CEO of Santhera, to discuss the CHMP decision will be held today, January 26, 2018, at 14:00 hrs CET. Dial-in participants are invited to call one of the following numbers about 10 minutes before the conference call is due to start.
+41 (0)58 310 50 00 (Europe)
+44 (0)207 107 0613 (UK)
+1 (1)631 570 5613 (USA)
1. Why has the CHMP reached a negative opinion for Raxone?
The Committee for Human Medicinal Products (CHMP), the people who assess new medicines on behalf of European Medicines Agency (EMA), acknowledged that the primary endpoint of the pivotal DELOS study, peak expiratory flow percent predicted, which is used in routine clinical practice was acceptable. The effect on clinical outcomes such as the reduction in rates of bronchopulmonary adverse events (respiratory infections) and hospitalization were also noted to be clinically important.
However, the CHMP has requested additional data to help support the link between the observed treatment effect on respiratory function outcomes during the trial and patient benefit. Simply stated, the CHMP would like additional data to support that the positive results of the trial translate into real world benefit for boys and men with Duchenne.
Importantly, the CHMP also recognized that patients with DMD in respiratory function decline and not able to take glucocorticoids represents a clinically distinct group of patients in high-unmet medical need. This means they are willing to review a therapy with data specifically focused on patients not taking glucocorticoids prior to obtaining data supporting safety and efficacy of the drug in patients taking glucocorticoids.
We are immensely grateful to the DMD community for their continued support and want to thank the community of patients, families, and healthcare professionals who have participated in our trials and supported us during the regulatory processes. We would not have been able to achieve what we have without their valued and ongoing input and we remain committed to working with them to develop Raxone for the treatment of respiratory function decline in DMD.
2. What were the specific concerns raised by the CHMP?
In its published summary of the meeting, the CHMP has cited robustness issues, common when conducting research in a small population, as the main reason why the assessment was challenging and a negative opinion reached.
Trials in rare disease commonly face challenges related to their size, how much is known about the progression of the disease when conducting the trial, and development of clinical trial endpoints – particularly with respect to studying respiratory function decline for which current knowledge is limited. Santhera is proud of the pioneering work conducted as one of the first trials in older boys and adults with Duchenne and focusing on one of the major causes of death in this population, respiratory function decline.
Santhera will continue to work with regulators to define a clear path forward to obtain additional data to strengthen the submission package and intends to submit a new application for marketing authorisation.
3. What are the next steps? Will there be a further appeal process?
The appeal decision is final. However, Santhera will continue its dialogue with regulators and seek scientific advice on how best to address the concerns of the CHMP to enable a new submission for marketing authorization as soon as possible.
4. Will this the impact the US regulatory plans?
No. Santhera continues to prepare for a New Drug Application for Raxone in the US and will update on the progress of that program as and when there is information to share.
5. What impact does this have on the early access programs?
Santhera will discuss with national regulatory authorities regarding patients with DMD who are already in an early access programs or receiving compassionate use supply, as required.
Santhera recognizes the importance of supporting the patient community and will work to ensure access in accordance to guidance from health authorities.
6. What are Santhera’s next steps to help patients with DMD?
Santhera will continue to generate and publish new data to provide further insights into the natural history and clinical impact of respiratory decline and its complications.
Santhera is fully committed to supporting patients with DMD who are in respiratory decline and will continue to raise awareness about the importance of regular monitoring, recognizing symptoms of respiratory decline, and access to specialized respiratory care for DMD.
Santhera will continue to work with regulators to define a clear path forward to strengthen the package with additional evidence and will aim to submit a new application for marketing authorisation.
7. What does this mean for the SIDEROS trial?
Santhera remains committed to the clinical development program for Raxone in DMD and will continue enrolling the SIDEROS trial. This negative opinion does not impact the ongoing Phase III SIDEROS study. The SIDEROS trial could provide additional evidence supporting the safety and efficacy of idebenone in treating respiratory function decline in DMD, specifically in boys and men taking glucoccorticoids.