Press Release: Santhera Announces Publication of Long-Term Clinical Data with Vamorolone in Patients with Duchenne Muscular Dystrophy

Pratteln, Switzerland, September 22, 2020 -- Santhera Pharmaceuticals

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

academic collaborators have published new open-label, long-term clinical

data on the safety, tolerability and efficacy of vamorolone in patients

with Duchenne muscular dystrophy (DMD). These 18-month treatment data

extend previously published 24-week treatment data, and show a reduction

of corticosteroid-specific side effects and sustained efficacy with

vamorolone including clinical improvement through the 18-month follow-up

period.

This publication in the journal PLOS Medicine [1] provides peer-reviewed

and detailed open-label data in patients with DMD treated for 18 months

with vamorolone. A multi-center, open-label, 24-week trial (VBP15-003;

[2, 3]) with a total 24-month long-term extension (VBP15-LTE; [4]) was

conducted by the Cooperative International Neuromuscular Research Group

(CINRG) and evaluated drug-related effects of vamorolone on motor

outcomes and corticosteroid-associated safety concerns. This publication

covers the 24-week Phase 2a trial (VBP15-003) and the first 12 months of

the open-label extension trial (VBP15-LTE) adding up to a total

treatment period of 18 months.

"This long-term study showed significant continued clinical improvement

of all outcomes measured over an 18-month follow-up period," said Edward

C. Smith, MD, Associate Professor of Pediatrics, Duke University, Durham

(North Carolina, USA), clinical investigator and lead-author of the

publication. "Treatment-related efficacy responses with vamorolone were

similar to those seen in an external control group with

corticosteroid-treated patients. Both 4-stair climb and 10-meter

run/walk tests were significantly improved when compared to

steroid-naïve natural history control subjects."

"Importantly, we also found that vamorolone did not show stunting of

growth seen with deflazacort and prednisone, and vamorolone also showed

fewer physician-reported adverse events such as mood disturbance,

excessive hair growth, and Cushingoid appearance," noted Eric Hoffman,

PhD, Vice President of Research at ReveraGen BioPharma, Inc. and

co-author of the study.

DMD trial participants (4 to <7 years at entry) treated with 2.0 or 6.0

mg/kg/day vamorolone for the full 18-month period (n=23) showed clinical

improvement of all motor outcomes from baseline to month 18 (time to

stand velocity, p = 0.012 [95% CI 0.010, 0.068 event/second]; run/walk

10 meters velocity, p < 0.001 [95% CI 0.220, 0.491 meters/second]; climb

4 stairs velocity, p = 0.001 [95% CI 0.034, 0.105 event/second];

6-minute walk test, p = 0.001 [95% CI 31.14, 93.38 meters]; North Star

Ambulatory Assessment, p < 0.001 [95% CI 2.702, 6.662 points]). Outcomes

in vamorolone-treated DMD patients (n = 46) were compared to

group-matched participants in the CINRG Duchenne Natural History Study

(corticosteroid-naïve, n = 19; corticosteroid-treated, n = 68) over

a similar 18-month period. Time to stand was not significantly different

between vamorolone-treated and corticosteroid-naïve participants (p

= 0.088; least squares [LS] mean 0.042 [95% CI --0.007, 0.091]), but

vamorolone-treated participants showed significant improvement compared

to group-matched corticosteroid-naïve participants for run/walk 10

meters velocity (p = 0.003; LS mean 0.286 [95% CI 0.104, 0.469]) and

climb 4 stairs velocity (p = 0.027; LS mean 0.059 [95% CI 0.007,

0.111]). The vamorolone-related improvements were similar in magnitude

to corticosteroid-related improvements. Corticosteroid-treated

participants showed stunting of growth, whereas vamorolone-treated trial

participants did not (p < 0.001; LS mean 15.86 [95% CI 8.51, 23.22]).

Physician-reported incidences of adverse events (AEs) for Cushingoid

appearance, hirsutism, weight gain, and behavior change were less for

vamorolone than published incidences for prednisone and deflazacort.

About Vamorolone

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

receptor as corticosteroids but modifies its downstream activity and as

such is a dissociative partial agonist [5-8]. This mechanism has the

potential to 'dissociate' efficacy from typical steroid safety concerns

and therefore vamorolone could emerge as a promising alternative to

existing corticosteroids, the current standard of care in children and

adolescent patients with DMD. There is substantial unmet medical need in

this patient group as high-dose corticosteroids have significant

systemic side effects that diminish patient quality of life. The

fully-enrolled, pivotal Phase 2b VISION-DMD trial (VBP15-004, [10, 11],

https://www.globenewswire.com/Tracker?data=yJqg2xznZ4-Y7_879LydYgP91G9a3on_t-gi-fdcjTqW43VdC9mirpbJ1HsrTEJ2noFx1R_jRx_HBR7YbMbIXcQI5GfBCYB75GHbUS56Ii3ZG4ds71FhBNJKh5gZaDlerPIBTZr5qZdxzaYhLVR4cg==

https://vision-dmd.info/2b-trial-information) is currently being

conducted at study sites across North America, Europe, Israel and

Australia and topline 6-month data are expected in Q2-2021, paving the

way for a US NDA submission in Q4-2021. Vamorolone has been granted

Orphan Drug status in the US and in Europe, and has received Fast Track

and Rare Pediatric Disease designations by the US FDA and Promising

Innovative Medicine (PIM) status from the UK MHRA.

Vamorolone was discovered by US-based ReveraGen BioPharma, Inc. and is

being developed in collaboration with Santhera, which owns worldwide

rights to the drug candidate in all indications. The vamorolone

development program has received funding from several international

non-profit foundations and patient organizations, the US National

Institutes of Health, the US Department of Defense and the European

Commission's Horizon 2020 program.

References:

[1] Smith E, et al. (2020). Efficacy and safety of vamorolone in

Duchenne muscular dystrophy: an 18-month interim analysis of a

non-randomized open-label extension study. PLOS Medicine,

https://www.globenewswire.com/Tracker?data=ZSQnH36bK71NSKDgB5vuCjOwOF8_LTHNexatzX4g9vq_7ahlLlZLFiQmmxGUIaUxLb392W4MQE-p1CBj679K4sGkz-n9dhisKqyFsm7xbCM=

Link

[2] Clinicaltrials.gov: An Extension Study to Assess Vamorolone in

Boys with Duchenne Muscular Dystrophy (DMD),

https://www.globenewswire.com/Tracker?data=ZSQnH36bK71NSKDgB5vuClYNTuJngwjV3w34sbAhlWf6HjzbxFAjr0GIrwr4Io39HW-5dm3flUbv3b6qc5SYAqCEkh0URoJEsH-TJS6QV-k=

Link

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

dystrophy shows dose-related improvement of muscle function. Neurology

93: e1312-e1323.

[4] Clinicaltrials.gov: Long-term Extension Study to Assess Vamorolone

in Boys with Duchenne Muscular Dystrophy (DMD),

https://www.globenewswire.com/Tracker?data=ZSQnH36bK71NSKDgB5vuCkfl5MDLnO5CQXSUbrzjYg9vU-JlRIK5CenZBG2Lenlr01bQyvoWiu0W-2hw0zal4Ew7sqmOgYwoqA31P0KRndU=

Link

[5] 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.

[6] Reeves EKM, et al (2013) VBP15: preclinical characterization of a

novel anti-inflammatory delta 9,11 steroid. Bioorg Med Chem

21(8):2241-2249

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

to treat inflammation and dystrophic cardiomyopathy. Life Science

Alliance DOI 10.26508/lsa.201800186.

[8] Liu X et al. (2020). Disruption of a key ligand-H-bond network

drives dissociative properties in vamorolone for Duchenne muscular

dystrophy treatment. Proc Natl Acad Sci USA.

https://www.globenewswire.com/Tracker?data=ZSQnH36bK71NSKDgB5vuCiecWm4cXzuVfCEuwEMHJmnnilJWbsAbUneiuPw8PZveHqypzm2TUusdWRqd2nKbgc_XWAe-QaQaE-qlzsNJwzU=

Link

[9] Press release "Santhera Exercises Option to Obtain Worldwide

Rights to Vamorolone in Duchenne Muscular Dystrophy and All Other

Indications", September 2, 2020,

https://www.globenewswire.com/Tracker?data=ZSQnH36bK71NSKDgB5vuCiCJfHJOvVCEgJD3ierrVvgOuvz-ZDbqgKq7tQdBJVowFHd4A0fUguPtdFbXqgIxapMZrdTZzR5_0M91GyYPB911uLVzE8fEvD4F4YkXtF9w9UJNhR-tT7CotecO0hhsXBOUIFeQjlmBlgtLyM4qlLU=

Link

[10] Clinicaltrials.gov: A Study to Assess the Efficacy and Safety of

Vamorolone in Boys with Duchenne Muscular Dystrophy (DMD),

https://www.globenewswire.com/Tracker?data=ZSQnH36bK71NSKDgB5vuCiomhGvYrA9LcDEVcQmWH7bRj6MrF7FwSEaGYWY-4gXPVZOyOuTtJ-C4EvdEBeMy0kbw-1vBHK5p6quwA0WKRbc=

Link

[11] Press release "Santhera Announces Full Enrollment of ReveraGen's

Pivotal VISION-DMD Study with Vamorolone in Duchenne Muscular Dystrophy",

September 11, 2020,

https://www.globenewswire.com/Tracker?data=ZSQnH36bK71NSKDgB5vuCvWVI64k2SWdg-zonkTpfyo9orGWZ7jkoLtfrrjpH_rbctMxc2tD0oZcVYHYk8dc-DQSzh2cFC2xhsJ_hY__Xhs_PCPK9SbDGtr5N991Hy91gaPWGg0-Sg9OXGCvyKsokUTbFh98reqJwO10r9L5JsM=

Link

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

currently under review by the European Medicines Agency. Santhera has an

exclusive license for all indications worldwide to vamorolone, a

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

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

as an alternative to 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

(MORE TO FOLLOW) Dow Jones Newswires

September 22, 2020 01:00 ET (05:00 GMT)