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2016-12-12

RedHill Biopharma Announces Phase IIa 48-Week Final Results Further Supporting Potential of RHB-104 in Multiple Sclerosis

RedHill Biopharma Ltd.
Press release

RedHill Biopharma Announces Phase IIa 48-Week Final Results Further Supporting
Potential of RHB-104 in Multiple Sclerosis

-- Thought to be autoimmune in nature, the multiple sclerosis (MS)
inflammatory process is also consistent with an infectious disease; The
CEASE-MS Phase IIa proof-of-concept (PoC), single-arm, open-label study was
designed with a series of exploratory endpoints to evaluate the safety and
potential efficacy of fixed oral-dose RHB-104 as an add-on therapy to
interferon beta-1a in 18 patients treated for relapsing-remitting multiple
sclerosis (RRMS); Patients underwent 24 weeks of RHB-104 add-on treatment
and a 24-week follow-up treatment period with interferon beta-1a, without
RHB-104
-- Top-line final (48 weeks) results are consistent with the previously
announced interim results suggesting meaningful positive safety and
clinical signals upon 24 weeks of treatment with RHB-104 as an add-on
therapy and support further clinical development
-- The encouraging top-line final results from patients who completed the
48-week study period demonstrate marked improvement over historical
self-control; The treatment effect of RHB-104 appears to be maintained
after discontinuing RHB-104:
-- Annualized relapse rate (ARR) was 0.0 at both 24 and 48 weeks in the
per-protocol (PP) population and 0.288 and 0.29, respectively, in the
modified intent-to-treat (mITT) population, comparing favorably with
previously reported pivotal studies of interferon beta-1a therapies
Avonex
®
(0.67)
[1]
and Rebif
®
(0.87-0.91)
[2]
; Only five relapses were noted throughout the study, four of which
occurred in a single subject
-- 100% of the PP patient population were relapse free at both 24 and 48
weeks and 88% and 93% of the mITT patient population were relapse free
at 24 and 48 weeks, respectively, comparing favorably with previously
reported pivotal data on the use of Rebif
®
(75%) in comparison with Avonex
®
(63%) as standalone first-line therapies
[3]
-- Expanded Disability Status Scale (EDSS) scores, a standard measure of MS
disability, indicate the disease was stable during the treatment period
and there was a signal of improvement; No increase in total EDSS scores
was observed in any of the patients during the treatment phase
-- Combined unique active lesions (CUAs) noted on MRI were almost entirely
T2 lesions; A reduction in total T2 lesion volume was observed at 24 and
48 weeks as compared to baseline, suggesting a decreased burden of
disease and comparing favorably with previously reported Avonex
®
[4]
and Rebif
®
[5]
data; Furthermore, no clinically significant change was observed for
total CUAs during the 24-week treatment period, which is supportive of a
stable disease
-- RHB-104 appeared safe and well-tolerated, with no drug-related serious
adverse events or other clinically relevant or unexpected adverse events
-- 2016 U.S. and worldwide sales of multiple sclerosis therapies were
estimated to exceed $12 billion and $18billion, respectively
-- A first Phase III clinical study with RHB-104 for Crohn’s disease is
ongoing (the MAP US study), with an independent safety-focused data and
safety monitoring board (DSMB) meeting on track by the end of the year
and a second meeting expected in the second quarter of 2017, with an
interim efficacy analysis of an option for early stop for success for
overwhelming efficacy

TEL-AVIV, Israel, Dec. 12, 2016 (GLOBE NEWSWIRE) -- RedHill Biopharma Ltd.
(NASDAQ:RDHL) (TASE:RDHL) (“RedHill” or the “Company”), a biopharmaceutical
company primarily focused on development and commercialization of late
clinical-stage, proprietary, orally-administered, small molecule drugs for
gastrointestinal and inflammatory diseases and cancer, today announced the
top-line final results from its CEASE-MS Phase IIa proof-of-concept (PoC)
clinical study evaluating fixed oral-dose RHB-104 in patients treated for
relapsing-remitting multiple sclerosis (RRMS).

Ira Kalfus, MD, Medical Director of RedHill and the CEASE-MS study said, “We
are very pleased with the final results from the CEASE-MS Phase IIa
proof-of-concept study with RHB-104 for relapsing-remitting multiple sclerosis
(RRMS). The findings from the study, including safety, clinical and MRI,
support the therapeutic potential of RHB-104 as an add-on therapy in RRMS. The
final results from patients who completed the 48-week study period demonstrate
marked improvement over historical self-control, suggesting the treatment
effect of RHB-104 is maintained after discontinuing RHB-104.” Dr. Kalfus added:
“Although designed as an exploratory proof-of-concept study in a very small
patient population and not powered for efficacy, the study results demonstrate
positive safety data and clinical signals, supporting additional studies to
better investigate the therapeutic potential of RHB-104 in RRMS. The results of
this study using targeted antibiotic therapy support the hypothesis that a
bacterially-induced dysregulated immune system plays a role in the pathogenesis
of multiple sclerosis. Importantly, a positive efficacy signal was seen in the
reduction of total T2 lesion volume at 24 and 48 weeks compared to baseline.
Moreover, despite the short duration of the study, EDSS scores at 24 weeks of
treatment with RHB-104 were stable, with suggestion of improvement, and upon
discontinuation of RHB-104, EDSS scores, while still stable, suggested a
possible deterioration. Notably, no patients experienced a worsening in total
EDSS while on treatment and a single patient experienced clinically relevant
deterioration following treatment, further supporting the therapeutic potential
of RHB-104 for the treatment of RRMS. RHB-104 was observed to be safe and
well-tolerated with no clinically relevant or unexpected adverse events,
reinforcing our confidence in this therapeutic candidate as we continue to
advance the ongoing Phase III MAP US study with RHB-104 for Crohn’s disease.
Further analysis will drive next steps in the development path of RHB-104 for
MS. We would like to thank the patients, investigators and clinical support
staff who participated in this important study.”

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the
central nervous system (CNS) with an unknown multifactorial etiology. Thought
to be autoimmune in nature, the MS inflammatory process is also consistent with
an infectious disease. RHB-104 is a proprietary, orally administered,
potentially groundbreaking antibiotic combination therapy with potent
intracellular, anti-mycobacterial and anti-inflammatory properties. The
completed CEASE-MS Phase IIa clinical study was a single-arm, open-label PoC
study evaluating fixed oral-dose RHB-104 as add-on therapy to interferon
beta-1a for the treatment of RRMS. This study followed positive pre-clinical
research findings and provides clinical evidence of RHB-104’s potential as a
treatment for MS. The study was designed as an uncontrolled, non-powered,
single-arm, open-label PoC study with the objective of evaluating the safety
and potential efficacy of RHB-104 using a series of exploratory measures. The
results presented in this press release remain subject to the Clinical Study
Report (CSR), to be finalized.

Study Design and Baseline Characteristics

CEASE-MS was a 48-week study, where patients underwent 24 weeks of RHB-104
treatment and a 24-week follow-up treatment period with interferon beta-1a,
without RHB-104 add-on. Interim results for this study were announced after the
24-week treatment phase was completed by all patients. All endpoints have been
reassessed for the final data analysis using patients as their own control for
analysis of interferon beta-1a treatment with and without add-on RHB-104
therapy.

18 patients suffering from RRMS were enrolled in the CEASE-MS study in two
sites in Israel, of which 17 patients who completed dose escalation were
included in the modified intent-to-treat (mITT) data set. One patient was
withdrawn from the study due to prohibited concomitant medication usage. The
patients had been treated with interferon beta-1a for an average of
approximately five years prior to enrollment in the study, experienced at least
one MS relapse within 12 months prior to enrollment or two MS relapses within
24 months prior to enrollment, and had an EDSS score of 6.0 or less at
screening, with a mean of 3.06. The per-protocol (PP) analysis included ten
patients, all of whom completed both the dose escalation and 48-week study
period without any major protocol deviations.

Annualized Relapse Rate (ARR)

In the 24-week treatment period, patients in the study experienced an
annualized relapse rate (ARR) of 0.0 in the per-protocol (PP) population and
0.29 in the mITT population. Notably, the ARR remained 0.0 in the PP population
throughout the 24-week post-treatment period as well. This Phase II data using
RHB-104 experimentally as an add-on therapy is encouraging in comparison with
previously reported studies of FDA-approved standalone therapies like Avonex®
and Rebif®.

The top-line final results from patients who completed the 48-week study period
demonstrated marked improvement over historical self-control. The treatment
effect of RHB-104 appears to be maintained after completion of treatment with
RHB-104.

In the 24-week treatment period of the study, patients in the study experienced
an ARR of 0.0 in the PP population and 0.288 in the mITT population. These
results compare favorably with previously reported values for both interferon
beta-1a therapies Avonex® and Rebif®. The pivotal study of Avonex® demonstrated
an ARR of 0.67[6], and a different Avonex® study reported ARRs of 0.53 and 0.31
in patients with and without previous history of disease modifying therapy,
respectively[7]. The pivotal study of Rebif® demonstrated an ARR of 0.87 - 0.91
(a relapse rate of 1.73 - 1.82 over 2 years, 44 mcg or 22 mcg dose-dependent),
respectively[8]. In separate studies, reported ARRs for Rebif® have ranged from
0.72 in the PRISMS-4 Long-Term Efficacy Study[9] and 0.39 as first line therapy
in the CARE-MS I study[10].

Relapse During the Study

100% of the PP patient population was relapse free throughout the study, while
88% of the mITT patient population was relapse free during the 24 weeks of
treatment with RHB-104 and 93% of the mITT patient population was relapse free
in the 24 weeks following RHB-104 treatment. Two patients experienced relapses
during the study. One between weeks f...

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