Press Release: Santhera and ReveraGen Announce New 2.5-year Treatment Data with Vamorolone in Duchenne Muscular Dystrophy

Pratteln, Switzerland, April 28, 2021 -- Santhera Pharmaceuticals (SIX:

SANN) and ReveraGen Biopharma announce new clinical data of 2.5-year

treatment outcome with vamorolone in patients with Duchenne muscular

dystrophy (DMD). These Phase 2a long-term treatment data demonstrate a

maintenance of treatment effect, equivalent to a delay of about two

years in decline for time to stand (TTSTAND) velocity, and confirm

safety and tolerability benefits of vamorolone over the 2.5-year follow

up period. Long-term treatment with vamorolone resulted in significantly

fewer corticosteroid-associated adverse events than reported in other

clinical trials with other steroids.

A sequence of studies investigated the safety, tolerability and

long-term treatment benefit with vamorolone and provide open-label data

in a total of 46 patients with DMD, aged 4 to up to 10 years (start/end

of treatment), of which 41 (89%) completed a 2.5 years treatment period.

48 participants initially completed a two-week multiple ascending dose

trial VBP15-002 [1], 46 of whom entered the open-label 6-month extension

VBP15-003 [2], covering a dose range of vamorolone of 0.25 to 6.0

mg/kg/day. All of the 46 patients completing the latter study entered

the 24-month long-term extension study VBP15-LTE [3] where all patients

eventually received doses of vamorolone of 2.0 to 6.0 mg/kg/day. The

total exposure to vamorolone treatment in these studies was 113 patient

years. The most commonly administered dose of vamorolone was 6.0

mg/kg/day. The studies, conducted by the Cooperative International

Neuromuscular Research Group (CINRG), evaluated drug-related effects of

vamorolone on timed motor function outcomes and

corticosteroid-associated safety concerns.

Maintenance of treatment effect indicates disease modifying potential of

long-term treatment with vamorolone

Previously reported findings [2] showed that patients treated with the

two highest dose levels of vamorolone (2.0 mg/kg/day or 6.0 mg/kg/day)

improved on average in their time to stand (TTSTAND) velocity by

approximately 0.05 rises/second after 6 months of treatment from

baseline, while patients treated with lower vamorolone doses or

steroid-naïve controls from the CINRG-DMD Natural History Study

(DNHS) showed no change. In practice, this change of 0.05 rises/second

in a velocity is equal to e.g. an improvement from 5 to 4 seconds or

from 8 to 5.7 seconds in the rise time from supine to standing. The

treatment effect of the two highest dose levels of vamorolone was

maintained at 0.05 rises/second at 2.5 years when compared to

age-matched steroid-naive patients from the CINRG-DNHS. These results

are equivalent to a delay of about two years in decline in TTSTAND

velocity, which is consistent with the treatment effect of

glucocorticoids seen in other studies [4, 5], and suggest disease

modifying potential of vamorolone treatment in DMD. A similar change in

trajectory was also observed for time to run/walk 10 meters (TTRW)

compared to steroid-naïve patients from CINRG-DNHS. Assessments of

6-minute walk test (6-MWT) was not conducted in an adequate number of

participants in CINRG-DNHS to allow for a comparison, however, patients

receiving long term treatment with vamorolone remained above their

average baseline value for 6-MWT after 2.5 years which further supports

the long-term efficacy of vamorolone.

Favorable tolerability profile of vamorolone with less

corticosteroid-typical side effects confirmed

The safety and tolerability of vamorolone at 2.5 years was consistent

with previously published 18-month data [3]. Both doses of 2.0 and 6.0

mg/kg/day were safe and well tolerated during 2.5 years of treatment in

DMD patients. Four out of the five patients who discontinued the study

did so for logistical reasons or switching to other trials and only one

patient discontinued from the study due to a disease-related adverse

event (muscle weakness). A longer treatment duration was not associated

with an increase in the incidence of treatment emergent adverse events.

Patients experiencing adverse weight gain on the 6.0 mg/kg/day dose

level (19% annual incidence rate), the most frequent steroid-associated

adverse event, were clinically managed by reducing the dose of

vamorolone to 4.0 or 2.0 mg/kg/day. This resulted in a reduction of the

annual incidence rate to 6%. Other typical adverse events seen

frequently in patients treated with corticosteroids such as Cushingoid

appearance, behavioral abnormalities, skin changes (such as acne) or

abnormal hair growth (hirsutism) were observed in only a few individual

patients or not at all. Incidence rates of these individual events did

not exceed 5% per year of treatment with vamorolone in the LTE.

Importantly there were no reports of stunted growth, commonly reported

in connection with corticosteroid treatment, over the entire follow up

period.

"We are very pleased with the results of this long-term follow-up which

show that treatment benefits of vamorolone are sustained over the

2.5-year follow-up period. Importantly, vamorolone was well tolerated

and we observed far fewer of the side effects typically seen with

corticosteroids in the clinic," said Eric Hoffman, PhD, President and

CEO at ReveraGen BioPharma. "We would like to thank all patients, their

caregivers and health care professionals for their much-valued

participation in these studies which, we are confident, will support our

approach to develop vamorolone as a novel treatment for this devastating

disease."

"These findings indicate the long-term maintenance of treatment effect

and disease modifying potential with vamorolone. We are equally excited

about the findings that vamorolone did not show stunting of growth

typically reported for other corticosteroids, and also resulted in

significantly fewer physician-reported adverse events which are common

reasons for corticosteroid treatment discontinuation," said Dario Eklund,

CEO of Santhera. "We are expecting the 6-month results from the pivotal

Phase 2b VISION-DMD study in Q2-2021 and are confident that they will

provide further evidence to establish vamorolone as an effective

treatment and valuable alternative to corticosteroids for the long-term

treatment for DMD."

Additional data analyses including comparisons to external control

datasets are planned and will be submitted to forthcoming congresses and

for journal publication.

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 [6-8]. 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. In the

pivotal Phase 2b VISION-DMD trial, the last patient has completed the

last visit of the 24-week, placebo- and active-controlled treatment

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

for a US NDA submission in Q1-2022. 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] Conklin et al. (2018). Pharmacol Res. 136:140-150.

[2] Hoffman EP et al. (2019). Neurology 93: e1312-e1323.

[3] Smith E, et al. (2020). PLOS Medicine, Link

https://www.globenewswire.com/Tracker?data=cPbvZiXJfTtluMNIXwi6JWmMvjHJwHvlv0HVi-Pre2E7RzZWnyOEKx9HS18W_xIHJb9ZPdkokpXoc6h4oZKWUd07IvR6c4ylaVqSX1XGaEI=

[4] McDonald CM et al. Lancet. 2018 Feb 3;391(10119):451-461.

[5] Matthews E et al. Cochrane Database Syst Rev. 2016; 5.

[6] Heier CR at al. (2013). EMBO Mol Med 5: 1569--1585.

[7] Reeves EKM, et al (2013). Bioorg Med Chem 21(8):2241-2249.

[8] Liu X, et al. (2020). Proc Natl Acad Sci USA 117:24285-24293.

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 has an exclusive license for all indications

worldwide to vamorolone, a first-in-class dissociative steroid 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 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 www.santhera.com.

Raxone(R) is a trademark of Santhera Pharmaceuticals.

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,

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April 28, 2021 01:00 ET (05:00 GMT)