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FDA Turns Down Santhera Pharmaceuticals’ Request for Accelerated Approval for Idebenone to Treat DMD

Background: Santhera Pharmaceuticals has been notified by the U.S. Food and Drug Administration (FDA) that the company must include results from its SIDEROS clinical trial at the time that it files a New Drug Application (NDA) for idebenone to treat Duchenne muscular dystrophy (DMD). Results from the ongoing phase 3, placebo-controlled trial of idebenone (brand name Raxone) in DMD patients who are receiving treatment with glucocorticoids (steroids), are not expected to be available until 2019, which could push back FDA review of the drug to 2020.

A phase 3 clinical trial called DELOS, conducted by Santhera in DMD patients who were not being treated with steroids, showed that treatment with idebenone significantly reduced the annual decline in Peak Expiratory Flow (a measure of lung function) compared to patients who received a placebo. Additional analysis from the study showed that when compared with those who were treated with placebo, trial participants who were treated with idebenone for one year had fewer bronchopulmonary adverse events such as upper respiratory tract infections and bronchitis.

Santhera had hoped that the results from the DELOS trial would support an NDA through the accelerated approval pathway for use of idebenone in patients who are not taking steroids, but following FDA guidance, will need to wait and submit data from its upcoming phase 3 SIDEROS trial as part of its filing as well.

Statement from MDA Scientific Program Officer Laura Hagerty, Ph.D.:

“Although this isn’t the news many had hoped for, MDA will continue our work to bring safe and effective therapy options to the Duchenne community. We are optimistic that viable treatment options are closer than ever before, and we will continue to do everything in our power to advocate on behalf of our families.”

“MDA is committed to bringing safe and effective treatments and cures to children and adults living with life-threatening neuromuscular diseases as quickly as possible. Today, new treatments in the pipeline are making their way through testing toward regulatory review. MDA will continue to work hand-in-hand with families, health care professionals, sister organizations, scientists and the FDA to move these treatments through the development process and hasten the day when there will be treatments available for all the diseases in our program.”

See below to read Santhera’s Press Release:

Santhera Updates on U.S. Regulatory Filing for Raxone® (idebenone) in Duchenne Muscular Dystrophy (DMD)

Liestal, Switzerland, July 14, 2016 – Santhera Pharmaceuticals (SIX: SANN) announces that it has received written correspondence from the U.S. Food and Drug Administration (FDA) on its proposed subpart H approval pathway for Raxone in DMD patients not taking concomitant glucocorticoids. Santhera had proposed that the planned SIDEROS trial would provide confirmatory evidence of efficacy in these patients whilst expanding the label to include the treatment of glucocorticoid-using patients.

From its review of this strategy, the FDA concluded that results from the SIDEROS trial, which is powered to detect a difference in the established surrogate endpoint Forced Vital Capacity percent predicted (FVC%p) in glucocorticoid-using patients, should be provided at the time of filing to support an NDA for the treatment of DMD patients irrespective of their glucocorticoid use status.

The protocol of the SIDEROS trial has previously been reviewed by the FDA which confirmed that this trial has the potential, if positive, to provide the necessary efficacy data, along with data from previous trials to support NDA filing in patients with DMD.

“While we are disappointed that the FDA does not support our plan to file an NDA for Raxone under subpart H for patients not using concomitant glucocorticoids, we now have clarity that successful completion of the SIDEROS trial will provide the necessary data to support NDA filing for Raxone in all DMD patients irrespective of the glucocorticoid use status,” commented Thomas Meier, PhD, CEO of Santhera. “Enrolment in the SIDEROS trial will start shortly and we are committed to working closely with the FDA, clinical experts and the DMD patient community to make Raxone available for all DMD patients in the U.S. as quickly as possible.”

About the SIDEROS Trial

SIDEROS is a Phase III double-blind, randomized, placebo-controlled trial of Raxone in Duchenne muscular dystrophy (DMD) patients receiving concomitant glucocorticoids. Patients with declining respiratory function on any stable glucocorticoid treatment scheme irrespective of the underlying dystrophin mutation or ambulatory status will be eligible for participation. Study participants will receive either Raxone (900 mg/day; given as 2 tablets 3 times a day with meals) or placebo for 78 weeks (18 months). The primary endpoint of the trial is change from baseline to week 78 in forced vital capacity % predicted (FVC%p). Secondary endpoints include changes from baseline in % predicted peak expiratory flow (PEF%p), time to first 10% decline in FVC, and change from baseline in inspiratory flow reserve. Patients completing the trial will be offered the opportunity to enroll in an open label extension study where all patients receive Raxone. It is currently expected that the results of the SIDEROS trial will become available in 2H 2019.

About Raxone® (Idebenone) in Duchenne Muscular Dystrophy and Regulatory Status

Duchenne muscular dystrophy (DMD) is one of the most common and devastating types of muscle degeneration and results in rapidly progressive muscle weakness. DMD is characterized by a loss of the protein dystrophin, leading to cell damage, impaired calcium homeostasis, elevated oxidative stress and reduced energy production in muscle cells. This results in progressive muscle weakness and wasting and early morbidity and mortality due to respiratory failure.

Idebenone is a synthetic short-chain benzoquinone and a cofactor for the enzyme NAD(P)H:quinone oxidoreductase (NQO1) capable of stimulating mitochondrial electron transport, reducing and scavenging reactive oxygen species (ROS) and supplementing cellular energy levels.

DELOS was a phase III, double-blind, placebo-controlled trial which randomized 64 patients, not taking concomitant glucocorticoids, to receive either Raxone (900 mg/day) or matching placebo. The trial met its primary endpoint and demonstrated that Raxone can slow the loss of respiratory function and reduces bronchopulmonary complications. The positive outcome of the Phase III DELOS study was published by Buyse et al., The Lancet 2015 385(9979):1748-57) and McDonald et al., Neuromuscular Disorders http://dx.doi.org/10.1016/j.nmd.2016.05.008.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is currently assessing a Marketing Authorization Application (MAA) for Raxone in DMD patients with respiratory function decline who are not taking concomitant glucocorticoids. The indication would include patients who previously were treated with glucocorticoids or in whom glucocorticoid treat-ment is not desired, not tolerated or is contraindicated. The MAA was recently submitted as a Type II variation of the company’s existing marketing authorization for Raxone. In September 2015, Raxone was approved for the treatment of visual impairment in adolescent and adult patients with Leber's hereditary optic neuropathy (LHON) in all EU member states, Norway, Iceland and Liechtenstein.

About Santhera

Santhera Pharmaceuticals (SIX: SANN) is a Swiss specialty pharmaceutical company focused on the development and commercialization of innovative pharmaceutical products for the treatment of orphan mitochondrial and neuromuscular diseases. Santhera's lead product Raxone® is authorized in the European Union for the treatment of Leber's hereditary optic neuropathy (LHON). For Duchenne muscular dystrophy (DMD), the second indication for Raxone®, Santhera has filed a Marketing Authorization Application (MAA) in the European Union. Santhera develops Raxone® in a third indication, primary progressive multiple sclerosis (PPMS), and omigapil for congenital muscu-lar dystrophy (CMD), all areas of high unmet medical need. For further information, please visit the Company's website www.santhera.com.

Raxone® and Catena® are trademarks of Santhera Pharmaceuticals.

For further information, contact:
Thomas Meier, PhD, Chief Executive Officer
Phone +41 61 906 89 64
thomas.meier@santhera.com

Christoph Rentsch, Chief Financial Officer
Phone +41 61 906 89 65
christoph.rentsch@santhera.com

US investor contact
Hans Vitzthum, LifeSci Advisors, LLC
Phone +1 212 915 2568
hans@lifesciadvisors.com

US Public Relations contact
Deanne Eagle, Planet Communications
Phone +1 917 837 5866
deanne@planetcommunications.nyc

Disclaimer / Forward-looking statements
This communication does not constitute an offer or invitation to subscribe for or purchase any secu-rities of Santhera Pharmaceuticals Holding AG. This publication may contain certain forward-looking statements concerning the Company and its business. Such statements involve certain risks, uncer-tainties and other factors which could cause the actual results, financial condition, performance or achievements of the Company to be materially different from those expressed or implied by such statements. Readers should therefore not place undue reliance on these statements, particularly not in connection with any contract or investment decision. The Company disclaims any obligation to update these forward-looking statements.

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