Press Release: Santhera Provides Update on the Ongoing Regulatory Review of Puldysa(R) (Idebenone) by the CHMP in Duchenne Muscular Dystrophy (DMD)

A conference call will be held today at 13:00 CEST, 12:00 BST, 07:00

EDT. Details are at the end of this statement.

Pratteln, Switzerland, May 29, 2020 -- Santhera Pharmaceuticals (SIX:

SANN) announces that the EMA's CHMP has granted a requested extension of

the clock-stop in the regulatory procedure for its conditional marketing

authorization (CMA) application for Puldysa(R) (idebenone) in Duchenne

muscular dystrophy (DMD). During this clock-stop, the Company is

evaluating the potential of conducting an interim analysis to test for

so-called overwhelming efficacy of its SIDEROS study with a view of

including the data in the review procedure and potentially completing

the trial early. This will result in a CHMP opinion in Q4 2020. A

positive early completion of the SIDEROS study would allow acceleration

of subsequent regulatory filings in the US and Europe by approximately

one year.

During its May meeting the CHMP accepted a requested extended clock-stop

to address the list of outstanding issues adopted at Day 180 of the

ongoing review procedure of the conditional marketing authorization

(CMA) application for Puldysa(R) (idebenone) in DMD for patients not

using concomitant glucocorticoids. This extends the review time into the

fourth quarter 2020.

Santhera recently communicated that it has completed enrollment into its

SIDEROS study. SIDEROS is 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 using concomitant

glucocorticoids. As previously announced, and given the strong powering

of SIDEROS, Santhera now intends to pursue the conduct of an interim

analysis by the independent Data and Safety Monitoring Board (DSMB) to

test if the trial can be stopped early due to overwhelming efficacy.

Under the scenario that overwhelming efficacy is demonstrated, the

outcome of the interim analysis would be added within the clock-stop to

the dossier currently under review by the CHMP to further enhance the

CMA data package. Furthermore, the study would be completed with the

option for trial participants to transfer into the open label extension

of SIDEROS, where all patients are treated with idebenone.

Positive interim data supporting overwhelming efficacy from the SIDEROS

study and a potential early completion of the study would also allow

acceleration of filings for a label including patients irrespective of

their glucocorticoid use status. Such NDA filing with the US FDA could

be accelerated by approximately one year. In Europe, subject to approval

in the indication currently under CHMP review for patients not using

concomitant glucocorticoids, such positive SIDEROS data could also

shorten time to a label extension to include glucocorticoid using DMD

patients by around one year.

"We are delighted about the completion of enrollment of the SIDEROS

study and hope to now be able to proceed with an interim analysis which

potentially paves the way for an earlier close of the trial," said Dario

Eklund, Chief Executive Officer of Santhera. "Despite the delay in our

plans to get a CMA approved resulting from the clock-stop, we are

convinced that this is the right strategy to both strengthen our current

filing dossier and also to accelerate time to market in the US, and in

the EU for patients using glucocorticoids."

Conference Call

Santhera will host a conference call today at 13:00 CEST / 12:00 BST /

07:00 EDT. Dario Eklund, CEO of Santhera, will discuss this update.

Participants are invited to call one of the following numbers 10-15

minutes before the conference call starts (no dial-in code is required):

Europe: +41 58 310 50 00

UK: +44 207 107 06 13

USA: +1 631 570 56 13

About Duchenne Muscular Dystrophy

DMD is one of the most common and devastating types of progressive

muscle weakness and degeneration starting at an early age and leading to

early morbidity and mortality due to respiratory failure. It is a

genetic, degenerative disease that occurs almost exclusively in males

with an incidence of up to 1 in 3,500 live male births worldwide. 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. With age, progressive

respiratory muscle weakness affecting thoracic accessory muscles and the

diaphragm causes respiratory disease, impaired clearance of airway

secretions, recurrent pulmonary infections due to ineffective cough, and

eventually respiratory failure. There is currently no treatment approved

for slowing loss of respiratory function in patients with DMD.

About Idebenone in Duchenne Muscular Dystrophy

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 is a Phase 3, double-blind, placebo-controlled 52-week study which

randomized 64 patients, not taking concomitant glucocorticoids, to

receive either idebenone (900 mg/day) or matching placebo. The study met

its primary endpoint, the change from baseline in peak expiratory flow

(PEF) expressed as percent of predicted, which demonstrated that

idebenone can slow the loss of respiratory function and reduces the risk

of bronchopulmonary adverse events [1-5]. Supportive data for idebenone

were shown in the Phase 2 double-blind, placebo-controlled DELPHI study

and its 2-year open-label extension study (DELPHI-E).

SYROS is a prospectively planned, retrospective collection of long-term

respiratory function data from 18 patients who completed the DELOS study

and subsequently received idebenone (900 mg/day) under Expanded Access

Programs (EAPs). The SYROS study showed that the previously observed

beneficial effect of idebenone in reducing the rate of respiratory

function decline was maintained for up to six years during treatment

[6].

SIDEROS, the largest currently ongoing clinical trial in DMD, is a

double-blind randomized placebo-controlled Phase 3 study evaluating the

efficacy of idebenone (900 mg/day) in delaying the loss of respiratory

function in DMD patients using concomitant glucocorticoids. The trial is

fully enrolled and an assessment of the potential of conducting an

interim analysis by the independent Data and Safety Monitoring Board

(DSMB) to test for overwhelming efficacy with a view of potentially

completing the trial early is ongoing. Further information is available

at ClinicalTrials.gov NCT#02814019.

References:

[1] Buyse et al. (2015), The Lancet 385:1748-1757

[2] McDonald et al. (2016), Neuromuscular Disorders 26:473-480

[3] Buyse et al. (2017), Pediatric Pulmonology 52:508-515

[4] Mayer et al. (2017), Journal of Neuromuscular Diseases 4:189-198

[5] Buyse et al. (2018), Journal of Neuromuscular Diseases 5: 419-430

[6] Servais et al. (2020), Neuromuscular Disorders 30: 5-16

About Santhera

Santhera Pharmaceuticals (SIX: SANN) is a Swiss specialty pharmaceutical

company focused on the development and commercialization of innovative

medicines for rare neuromuscular and pulmonary diseases with high unmet

medical need. Santhera is building a Duchenne muscular dystrophy (DMD)

product portfolio to treat patients irrespective of causative mutations,

disease stage or age. A marketing authorization application for

Puldysa(R) (idebenone) is currently under review by the European

Medicines Agency. Santhera has an option to license vamorolone, a

first-in-class anti-inflammatory drug candidate with novel mode of

action, currently investigated in a pivotal study in patients with DMD

to replace standard corticosteroids. The clinical stage pipeline also

includes lonodelestat (POL6014) to treat cystic fibrosis (CF) and other

neutrophilic pulmonary diseases, as well as omigapil and an exploratory

gene therapy approach targeting congenital muscular dystrophies.

Santhera out-licensed ex-North American rights to its first approved

product, Raxone(R) (idebenone), for the treatment of Leber's hereditary

optic neuropathy (LHON) to Chiesi Group. For further information, please

visit

https://www.globenewswire.com/Tracker?data=9zaqYh8ZPyNhWKjif2c6TKm-PNSV8KvSq9aJ4kV_izxqyeLeXblNgVkHpkDmwhYLIRPFVivB_9BEf6If4meN4A==

www.santhera.com.

Raxone(R) and Puldysa(R) are trademarks of Santhera Pharmaceuticals.

For further information please contact:

https://www.globenewswire.com/Tracker?data=Bxu70dpKTAPOFmllbJLA9dVpFpVGJDGKZvnGPsBBbYGJUV8cepAPEOaSjm6fUpfbP1ohK8hDGgAeAnuW11Gl9TB2jS4Z2_KLd0NMfU-cxrZA6FfdiP2BgClQxUz7kfFj

public-relations@santhera.com or

Eva Kalias, Head External Communications

Phone: +41 79 875 27 80

eva.kalias@santhera.com

Disclaimer / Forward-looking statements

This communication does not constitute an offer or invitation to

subscribe for or purchase any securities of Santhera Pharmaceuticals

Holding AG. This publication may contain certain forward-looking

statements concerning the Company and its business. Such statements

involve certain risks, uncertainties 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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May 29, 2020 01:00 ET (05:00 GMT)