Der Spiegel

Dienstag, 21. Januar 2020


GlobeNewswire: Encouraging Phase 2 data on cenerimod - Idorsia's S1P1 receptor modulator currently investigated for SLE - presented at ACR 2019

11.11.2019, 07:00 Uhr

Encouraging Phase 2 data on cenerimod - Idorsia's S1P1 receptor modulator
currently investigated for SLE - presented at ACR 2019 A Phase 2 safety study
showed that cenerimod reduced circulating lymphocytes in a dose-dependent
manner and was safe and well tolerated at doses up to 4 mg in patients with
systemic lupus erythematosus (SLE). Exploratory analyses indicated an
encouraging numerical reduction in the modified SLEDAI-2K, an important measure
of disease activity and in anti-dsDNA antibodies. The company is currently
running a multiple-dose, efficacy and safety study with cenerimod for the
treatment of adult patients with moderately to severely active,
autoantibody-positive SLE.

Allschwil, Switzerland - November 11, 2019
Idorsia Ltd (SIX: IDIA) today announced that data from a Phase 2 study with
cenerimod, a selective sphingosine-1-phosphate 1 (S1P 1 ) receptor modulator,
were presented at the 2019 American College of Rheumatology (ACR) / Association
for Rheumatology Professionals (ARP) Annual Meeting in Atlanta, Georgia, US.

Systemic lupus erythematosus (SLE), the most common form of lupus, is an
autoimmune disease. In SLE, the body's immune system malfunctions and attacks
the body's own tissues, which can affect the skin, joints, gut, blood cells,
lungs, and other organs. While the cause of SLE is not fully known, T and B
lymphocytes are considered the key immune system cells that play a key role in
the development of SLE.

Cenerimod is a selective sphingosine-1-phosphate 1 (S1P 1 ) receptor
modulator, which potentially offers a novel approach for SLE - a disease with
limited treatment options. Idorsia is investigating cenerimod, an oral
once-daily tablet in patients with SLE. Cenerimod has the potential to add a
distinct mechanism to the treatment armamentarium for this underserved patient

Martine Clozel, MD and Chief Scientific Officer, commented:
"I am very encouraged by the excellent data presented with cenerimod, the
result of 20 years of research in our labs. As expected, we saw a
dose-dependent reduction in lymphocyte counts in patients with lupus. Perhaps
more importantly, we saw that the antibody-producing B-cells, which are
elevated in patients with lupus and critical to the disease processes, were
markedly reduced. In the limited current treatment landscape, I believe that
the properties of cenerimod and the mechanism of S1P 1 receptor modulation
provides significant potential to address the pathophysiology of lupus,
reducing circulating autoreactive T and B cells thereby stopping the production
of pathogenic autoantibodies."

Phase 2 study results presented at 2019 ACR/ARP Annual Meeting
Viktoria Hermann, MD from Idorsia gave an oral presentation entitled
"Cenerimod, a Selective S1P 1 Receptor Modulator, in Systemic Lupus

Abstract : Hermann V, et al. First Use of Cenerimod, a Selective
sphingosine-1-phosphate 1 (S1P 1 ) Receptor Modulator, for the Treatment of
Systemic Lupus Erythematosus: A Double-Blind, Randomised, Placebo-Controlled,
Phase II, Proof-of-Concept Study [abstract]. Arthritis Rheumatol. 2019; 71
(suppl 10).

Aberrantly activated T- and B-lymphocytes play a major pathophysiological role
in SLE. Cenerimod, a potent, selective sphingosine-1-phosphate 1 receptor
modulator, blocks the egress of lymphocytes from lymphoid organs, thereby
reducing their availability, thus providing rationale for development. The
study investigated the effect of cenerimod on circulating lymphocytes, disease
activity, safety and pharmacokinetics in SLE patients.

The study was conducted in two parts, A and B, which were separated by an
independent safety review. Patients with SLEDAI-2K score ≥2 points for
mucocutaneous or musculoskeletal manifestations and positive serum test for ANA
or anti-dsDNA antibodies were randomized evenly in Part A to cenerimod 0.5, 1,
2 mg or placebo once daily and 3:1 in Part B to cenerimod 4 mg or placebo
once-daily and treated for 12 weeks. All 67 patients (A: 49; B: 18) met at
least 4 ACR criteria in the past, 70% had 4 to 11 ACR criteria ongoing at
screening. Mean (SD) mSLEDAI-2K was 7.7 (±3.1) at baseline. Predefined Day 1
safety assessments included heart rate (HR) monitoring and hourly 12-lead ECG
monitoring (pre-dose, to 6 hours post-dose). Endpoints included
treatment-emergent adverse events (TEAEs), changes in total lymphocyte count,
SLEDAI-2K score (modified [mSLEDAI] to exclude leucopoenia), anti-dsDNA
antibody, a disease relevant biomarker, and pharmacokinetic assessments.


Part A included 49 patients (12:12:13:12 receiving cenerimod 0.5, 1, 2 mg or
placebo, respectively); Part B included 18 patients (13 cenerimod 4 mg; 5
placebo). Cenerimod dose-dependently reduced total lymphocyte count from
baseline to end of treatment (EOT; p < 0.001). In pairwise comparisons,
cenerimod 1, 2, and 4 mg significantly decreased lymphocytes versus placebo
(all p < 0.001). Exploratory analyses indicated clinical and biological
improvement with cenerimod 4 mg with an estimated mean treatment effect on
change from baseline to EOT in mSLEDAI-2K score of −2.420 (p=0.0306), and a
decrease in anti-dsDNA of −28.80 U/mL (p=0.0146) compared with placebo. All
treatment groups reported similar and non-dose-related rates of TEAEs
(cenerimod 0.5: 41.7%; 1: 41.7%; 2: 46.2%; 4 mg: 38.5%; and placebo: 58.8%).
After the first dose, cenerimod induced minimal, transient and dose-dependent
decreases in HR; no patient had an HR < 40 bpm at any time post baseline. Small
decreases in pulmonary function, not dose-related, were observed in
cenerimod-treated patients at EOT. Cenerimod did not increase blood pressure or
show any effects on laboratory variables. Trough plasma concentrations revealed
that steady-state conditions were reached after 4-8 weeks of once-daily dosing
and dose-proportionality was observed.

The results of this study have recently been published as a peer-reviewed
manuscript in Lupus Science & Medicine:

Hermann V, Batalov A, Smakotina S, et al. First use of cenerimod, a selective
S1P 1 receptor modulator, for the treatment of SLE: a double-blind, randomised,
placebo-controlled, proof-of-concept study. Lupus Science & Medicine
2019;6:e000354. doi:10.1136/lupus-2019-000354

Guy Braunstein, MD and Head of Idorsia Global Clinical Development, commented:
"This was the first study to investigate cenerimod in patients with SLE and
confirmed its lymphocyte lowering effects in this patient population.
Considering this was a small, 12-week study in patients with mild-to-moderate
SLE, we were encouraged by the early signs of reduced disease activity. We are
now investigating whether this translates into clinical efficacy in the ongoing
longer-term efficacy and safety study."

In addition to the Phase 2 data, posters already presented have highlighted
further results of a qualitative study of fatigue in SLE and preclinical
studies with cenerimod: Assessment of Fatigue in Adults with Moderate to Severe
Systemic Lupus Erythematosus (SLE): A Qualitative Study to Explore the Content
Validity of a Fatigue Questionnaire
Abstract : Mannix S, et al. Arthritis Rheumatol. 2019; 71 (suppl 10).
Cenerimod, a Potent and Selective Sphingosine-1-Phosphate Receptor 1 Modulator,
Controls Systemic Autoimmunity and Organ Pathology in Mouse Models of Systemic
Lupus Erythematosus and Sjögren's Syndrome
Abstract : Gerossier E, et al. Arthritis Rheumatol. 2019; 71 (suppl 10). In
Vitro Characterization of the Effect of Cenerimod, a Potent and Selective
Sphingosine-1-Phosphate Receptor 1 (S1P 1 ) Modulator, on S1P 1 Receptor
Expression, Receptor Internalization, and Migration of Primary Human T cells in
the Presence or Absence of Glucocorticoids
Abstract : Kulig P, et al. Arthritis Rheumatol. 2019; 71 (suppl 10).

A fourth poster is still to be presented on Tuesday, November 12, 2019:
Cenerimod, a Potent, Selective and Orally Active Sphingosine-1-phosphate
Receptor 1 Modulator, Reduced Blood Antibody-secreting Cells in Patients with
Abstract : Strasser D, et al. Arthritis Rheumatol. 2019; 71 (suppl 10).

In December 2018, Idorsia initiated a multiple-dose, efficacy and safety study
with cenerimod for the treatment of adult patients with moderately to severely
active, autoantibody-positive SLE. The multicenter, randomized, double-blind,
placebo-controlled, parallel-group study will enroll around 500 patients, who
will be randomized into four cenerimod treatment arms: 0.5, 1, 2, and 4 mg
once-daily orally or placebo for up to 12 months. Patients will receive study
treatment in addition to background SLE therapy, which will be kept as stable
as possible to avoid confounding the treatment effect. The study aims to
validate the appropriate dose, patient population and endpoints for further
development in SLE.

In December 2017, the US FDA designated the investigation of cenerimod for the
treatment of SLE as a Fast Track development program. The Fast Track
designation is intended to promote communication and collaboration between the
FDA and the company for drugs that treat serious conditions and fill an unmet
medical need.


Notes to the editor

About systemic lupus erythematosus
SLE - known more simply as "lupus" since it is the most common form of lupus -
is an autoimmune disease, which means that the body's immune system
malfunctions and attacks the body's own tissues, causing inflammation and organ
damage. Some autoimmune diseases affect individual organs, but in the case of
lupus, most parts of the body can be affected: most commonly the skin, joints,
gut, blood cells, and lungs, as well as the brain, heart, and kidneys.

Lupus can range from mild to life-threatening and can randomly become worse
(so-called 'flare ups') and then better again, which can make living with lupus
unpredictable and its impact on day-to-day life wide-ranging. Around five
million people worldwide have a form of lupus and while it affects people of
all races, genders, and ages, as much as ninety percent of diagnosed cases are
in women. The condition is also more common in people of Afro-Caribbean and
Asian origin compared to Caucasians and is likely to affect these ethnic groups
more severely.

There is no cure for lupus. Most people with lupus are prescribed a
combination of different medications including anti-inflammatory, anti-malarial
drugs, corticosteroids, immunomodulators.

Key scientific literature Hermann V,  et al. Lupus Science & Medicine
2019;6:e000354. doi:10.1136/lupus-2019-000354 Juif P-E,et al. Int. J. Mol. Sci.
2017, 18, 2636; doi:10.3390/ijms18122636 Piali L, et al. Pharmacol Res
Perspect. 2017 Dec;5(6). Borchers AT, et al. Autoimmun Rev. 2010; 9(5):A277-87.
Pons-Estel GJ, et al. Semin Arthritis Rheum. 2010; 39(4):257-68. Govoni M, et
al. Lupus. 2006; 15:110-113. Rahman A, Isenberg DA. N Engl J Med. 2008;
358:929-39. Abu-Shakra M, et al. J Rheumatol 1995; 22(7):1259-64.

About Idorsia
Idorsia Ltd is reaching out for more - We have more ideas, we see more
opportunities and we want to help more patients. In order to achieve this, we
will develop Idorsia into one of Europe's leading biopharmaceutical companies,
with a strong scientific core.

Headquartered in Switzerland - a biotech-hub of Europe - Idorsia is
specialized in the discovery and development of small molecules, to transform
the horizon of therapeutic options. Idorsia has a broad portfolio of innovative
drugs in the pipeline, an experienced team, a fully-functional research center,
and a strong balance sheet - the ideal constellation to bringing R&D efforts to
business success.

Idorsia was listed on the SIX Swiss Exchange (ticker symbol: IDIA) in June
2017 and has over 750 highly qualified specialists dedicated to realizing our
ambitious targets.

For further information, please contact
Andrew C. Weiss
Senior Vice President, Head of Investor Relations & Corporate Communications
Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, CH-4123 Allschwil
+41 58 844 10 10

The above information contains certain "forward-looking statements", relating
to the company's business, which can be identified by the use of
forward-looking terminology such as "estimates", "believes", "expects", "may",
"are expected to", "will", "will continue", "should", "would be", "seeks",
"pending" or "anticipates" or similar expressions, or by discussions of
strategy, plans or intentions. Such statements include descriptions of the
company's investment and research and development programs and anticipated
expenditures in connection therewith, descriptions of new products expected to
be introduced by the company and anticipated customer demand for such products
and products in the company's existing portfolio. Such statements reflect the
current views of the company with respect to future events and are subject to
certain risks, uncertainties and assumptions. Many factors could cause the
actual results, performance or achievements of the company to be materially
different from any future results, performances or achievements that may be
expressed or implied by such forward-looking statements. Should one or more of
these risks or uncertainties materialize, or should underlying assumptions
prove incorrect, actual results may vary materially from those described herein
as anticipated, believed, estimated or expected.

Anhang Medienmitteilung PDF

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