Press Release: Santhera Announces Full Enrollment of ReveraGen's Pivotal VISION-DMD Study with Vamorolone in Duchenne Muscular Dystrophy

Pratteln, Switzerland, September 11, 2020 -- Santhera Pharmaceuticals

(SIX: SANN) announces that partner ReveraGen Biopharma Inc. has

completed enrollment into the pivotal VISION-DMD study with vamorolone

in patients with Duchenne muscular dystrophy (DMD). Subject to a

positive study outcome, this could allow for a regulatory submission to

the US FDA in the fourth quarter of 2021 with the potential to offer an

alternative to current standard of care in young boys with DMD.

The 48-week Phase 2b VISION-DMD study (VBP15-004; clinicaltrials.gov:

NCT03439670 [1]) is designed as a pivotal trial to demonstrate efficacy

and safety of vamorolone administered orally at doses of 2.0 mg/kg/day

and 6.0 mg/kg/day versus prednisone 0.75 mg/kg/day and placebo in

ambulant boys ages 4 to <7 years with DMD. Efficacy outcome measures

after the first 24-week treatment period are muscle strength and motor

function outcomes with Time to Stand test (TTSTAND) as the primary study

endpoint. Additional analyses compare various safety and tolerability

markers between the vamorolone dose groups, placebo and prednisone. The

second 24-week treatment period where all patients receive one of two

vamorolone doses will evaluate the persistence of effect in the longer

term. In addition to efficacy, the study aims to confirm the favorable

tolerability profile of vamorolone with the potential to offer an

alternative to current standard of care. Although glucocorticoids are

part of the current care recommendations for DMD, their adverse effect

profile limits their use.

With the current number of 121 patients recruited, the VISION-DMD study

has reached its pre-planned enrollment target. The last patient is

expected to complete the first 24-week treatment period in the first

quarter of 2021 with a topline data readout in the second quarter of

2021. Subject to positive results of this first 24-week treatment period,

this would pave the way for a regulatory submission to the US FDA in the

fourth quarter of 2021.

Vamorolone has been granted Orphan Drug status in the US and in Europe,

and has received Fast Track and Rare Pediatric Disease designations from

the US FDA and Promising Innovative Medicine (PIM) status from the UK

MHRA. On September 2, Santhera signed agreements with ReveraGen and

Idorsia that granted Santhera an exclusive license to vamorolone for all

indications worldwide [2].

"We are very pleased having achieved full enrollment of our pivotal

trial with vamorolone in patients with Duchenne muscular dystrophy,"

said Eric Hoffman, PhD, Vice President of Research at ReveraGen

BioPharma. "On behalf of the entire study team we would like to thank

patients and their families for their enthusiastic engagement to help

advance the clinical development of vamorolone. We also thank

investigators and study site personnel for their interest and commitment

in completing this study as planned."

"We congratulate ReveraGen on this accomplishment of fully enrolling the

VISION-DMD trial, in times where the conduct of any clinical trial is

very challenging for patients and families, study sites and study

personnel," said Kristina Sjöblom Nygren, MD, Chief Medical Officer

and Head of Development at Santhera. "It is already clear from existing

data from previous studies that vamorolone has tremendous therapeutic

potential for patients with Duchenne muscular dystrophy and we are

looking forward to the outcome of the 6-month randomized, placebo- and

prednisone-controlled period of the VISION-DMD trial."

About Vamorolone

Vamorolone is a first-in-class drug candidate that binds to the same

receptors as corticosteroids but modifies the downstream activity of the

receptors [3, 4]. This has the potential to 'dissociate' efficacy from

typical steroid safety concerns and therefore could emerge as a valuable

alternative to existing corticosteroids, the current standard of care in

children and adolescent patients with DMD. There is significant unmet

medical need in this patient group as high dose corticosteroids have

significant systemic side effects that detract from patient quality of

life. Vamorolone is being developed by US-based ReveraGen BioPharma Inc.

with participation in funding and design of studies by several

international non-profit foundations, the US National Institutes of

Health, the US Department of Defense and the European Commission's

Horizon 2020 program.

About the clinical development program of Vamorolone in patients with

DMD

The clinical development program with vamorolone in patients with DMD

was initiated following a clinical pharmacology study (VBP15-001) in

healthy volunteers in which biomarker assessments indicated reduced

occurrence of side effects typical for traditional corticosteroid drugs

like bone fragility, metabolic disturbance, immune suppression [5].

The Phase 2a program with vamorolone consisted of two studies that were

conducted back-to-back in 48 boys with DMD aged 4 to <7 years (VBP15-002

and VBP15-003). These studies with a combined duration of 6 months

investigated the efficacy, safety and tolerability of oral

administration of vamorolone at doses of 0.25, 0.75, 2.0 and 6.0

mg/kg/day (12 boys per treatment group). Data from these studies

reported that vamorolone was safe and well tolerated over a period of 6

months with dose- and time-related improvements in various timed

function tests and motor function outcomes [6, 7]. Vamorolone treatment

led to increased serum levels of osteocalcin, a biomarker of bone

formation, suggesting possible reduction of bone morbidities typically

associated with corticosteroids. Biomarker outcomes for adrenal

suppression and insulin resistance also indicated better tolerability of

vamorolone treatment, relative to published studies of corticosteroid

therapy.

All 46 patients who completed the VBP15-003 study requested to continue

vamorolone treatment in the long-term extension, rather than transition

to corticosteroids. This 24-month long-term open-label extension study

(VBP15-LTE) study enabled dose escalation and de-escalation at the

preference of the physician and family and the majority of

physicians/families chose treatment at the highest tested dose of

vamorolone by the end of the VBP15-LTE study.

The now fully enrolled, Phase 2b VISION-DMD trial (VBP15-004)

complements previously conducted clinical studies in DMD. The study is

currently being conducted at over 30 sites across North America, Europe,

Israel and Australia. For more information:

https://www.globenewswire.com/Tracker?data=YGOmHP3HuFALK4Yza9DTbqwgB7G5g2ecLCyUtGzT5d2BHTOgXjUDwo1FbmFK989Bd2UdJ2y57YvinZjGOtbPocgfJYTYht3q0IobnIQ4pn3qvAW_HdDJm7sAZVQl_kCt5jxrV6Iymxtult9yAOgH8KcyeBH_6J9YZkXG9KrZpBk=

https://vision-dmd.info/2b-trial-information.

References:

[1]

https://www.globenewswire.com/Tracker?data=YGOmHP3HuFALK4Yza9DTbpkV8Otn4tOkG-Pq6fu2ZvxDpvJ0FESfVEOrY6dqgklJgEgHuLT92Ktz45PXxVthD0Z8-QqQOy0QrBvb8BUhJyPbZ-k_Smkb6Xu1Ol0O4ViFO9tWa1pbVackir3JAPJsCWcCYm2li-EcesoivSKFxO7o7aQI8MFbQmjbaA_xroDtxRnDat-7b44BXVhymSdWKHMEOtsLy3wVvfgO7n1C40IHil2dmTuC8Iwnp2tRGTLp6gpJO5cCgswhXzIzvgaroA==

https://www.clinicaltrials.gov/ct2/show/NCT03439670?term=vamorolone&draw=2&rank=3

[2] Press release "Santhera Exercises Option to Obtain Worldwide Rights

to Vamorolone in Duchenne Muscular Dystrophy and All Other Indications",

September 2, 2020, accessible

https://www.globenewswire.com/Tracker?data=nQGJHLEJwX4VvycZwdzArj0lsDP0l8ooeR-QzIvusAzGd-mBYfU8BcOIoQVWcODiHpUB2l7-MfUu8r9XL7kv0BkITV8lniLEvJ4FERp6ECd8YrXqU-uJUu6xSeuR0ALyLAt_vNndoAOcOFIUlwnnFRq5U97Br7J7VD9puLJWPlc=

here.

[3] Heier CR at al. (2013). VBP15, a novel anti--inflammatory and

membrane--stabilizer, improves muscular dystrophy without side effects.

EMBO Mol Med 5: 1569--1585.

[4] Heier CR et al. (2019). Vamorolone targets dual nuclear receptors to

treat inflammation and dystrophic cardiomyopathy. Life Science Alliance

DOI 10.26508/lsa.201800186.

[5] Hoffman EP et al. (2018). Phase 1 trial of vamorolone, a

first-in-class steroid, shows improvements in side effects via

biomarkers bridged to clinical outcomes. Steroids 134: 43-52.

[6] Conklin LS et al. (2018). Phase IIa trial in Duchenne muscular

dystrophy shows vamorolone is a first in-class dissociative steroidal

anti-inflammatory drug. Pharmacological Research 136:140-150.

[7] Hoffman EP et al. (2019). Vamorolone trial in Duchenne muscular

dystrophy shows dose-related improvement of muscle function. Neurology

93: e1312-e1323.

About ReveraGen BioPharma

ReveraGen was founded in 2008 to develop first-in-class dissociative

steroidal drugs for Duchenne muscular dystrophy and other chronic

inflammatory disorders. The development of ReveraGen's lead compound,

vamorolone, has also been supported through partnerships with

foundations worldwide, including Muscular Dystrophy Association USA,

Parent Project Muscular Dystrophy, Foundation to Eradicate Duchenne,

Save Our Sons, JoiningJack, Action Duchenne, CureDuchenne, Ryan's Quest,

Alex's Wish, DuchenneUK, Pietro's Fight, Michael's Cause, and Duchenne

Research Fund. ReveraGen has also received generous support from the US

Department of Defense CDMRP, National Institutes of Health (NCATS, NINDS,

NIAMS), and European Commission (Horizon 2020).

https://www.globenewswire.com/Tracker?data=MFS78wFkOhQeRa6o6NV05ga28DL2su5sty9jES9Cr4209A22xSlF9DUy7nQ7Nl1ee62kPxGFDqzXLkY3OkokoSZ8TJP4XKMgJBZqYkB2sI4=

www.reveragen.com

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 from early to late disease stages,

irrespective of causative mutations, ambulatory status or age. A

marketing authorization application for Puldysa(R) (idebenone) is

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