ABLYNX'S ANTI-IL-6R NANOBODY, ALX-0061, SHOWS EXCELLENT 24 WEEK SAFETY AND EFFICACY RESULTS IN A PHASE II CLINICAL TRIAL IN RHEUMATOID ARTHRITIS
* ACR20, ACR50 and ACR70 scores of up to 100%, 75% and 63% respectively
* Up to 75% of patients in DAS28 remission
* Attractive safety profile at all administered doses
* No anti-drug antibodies detected
* No disease progression as determined by MRI radiography
Results will be discussed during a webcast presentation today at 16h CET, 10 am
EST
Click here to register, call number +32 (0)2 620 01 38
GHENT, Belgium, 13 February 2013 - Ablynx [Euronext Brussels: ABLX] today
announced efficacy and safety data for its anti-IL-6R Nanobody, ALX-0061, at the
24 week final analysis of the Phase II part of a combined Phase I/II study in
patients with moderately to severely active rheumatoid arthritis (RA) on a
stable background of methotrexate.
In this Phase II part, 37 RA patients were recruited and were randomised to
three dose groups of intravenously administered ALX-0061 (1mg/kg Q4W[1], 3mg/kg
Q4W and 6mg/kg Q8W(1)) or to placebo. A total of 34 patients were eligible for
determination of efficacy parameters at the 12 week interim period, and all
these patients continued the study until week 24.
Depending on the patient's disease status at week 10, the monthly dose was
increased (from 1mg/kg to 3mg/kg; or from 3mg/kg to 6mg/kg) or the dosing
regimen intensified (from 6mg/kg Q8W to 6 mg/kg Q4W), and patients on placebo
could start monthly ALX-0061 treatment at 3mg/kg. The vast majority of patients
(86%, N=24) completed the study at their ALX-0061 starting regimen (the
'unmodified' group), for 4 patients the dosing regimen was modified (the
'modified' group) and 3 patients were switched from placebo to ALX-0061
treatment (the 'switchers').
At all doses tested, ALX-0061 was well-tolerated and the safety profile compared
favourably to data reported for other biological DMARDs[2]. No clinically
relevant neutropenia (moderate or severe decrease in neutrophils, a type of
white blood cell), no clinically significant increases in lipid levels
(cholesterol and triglycerides) were observed, and there were no serious
infections. Infrequent elevation of liver enzymes were reported; the events were
transient, generally mild to moderate, and did not result in a discontinuation
of the treatment. Additionally, the side effect profile of ALX-0061 did not
change with increased dose or treatment duration and no anti-drug antibodies
were detected.
The efficacy results for the 'unmodified' patient population at week 24 are
presented below:
+---------------------+----------+----------+----------+-------------------+
|Efficacy parameter |1mg/kg Q4W|3mg/kg Q4W|6mg/kg Q8W|Pooled 'unmodified'|
| |(N=8) |(N=8) |(N=8) |(N=24) |
+---------------------+----------+----------+----------+-------------------+
|ACR20[3] |75% |100% |75% |83% |
+---------------------+----------+----------+----------+-------------------+
|ACR50 |63% |75% |75% |71% |
+---------------------+----------+----------+----------+-------------------+
|ACR70 |50% |63% |63% |58% |
+---------------------+----------+----------+----------+-------------------+
|DAS28 remission[4] |50% |75% |63% |63% |
+---------------------+----------+----------+----------+-------------------+
|Boolean remission[5]Â |25% |38% |25% |29% |
+---------------------+----------+----------+----------+-------------------+
The efficacy results at week 24 for the 'modified' patient population and
patients switching from placebo to ALX-0061 treatment are presented below:
+--------------------+-------------------+--------------------+
| Efficacy parameter | Pooled 'modified' | Pooled 'switchers' |
| | (N=4) | (N=3) |
+--------------------+-------------------+--------------------+
| ACR20 | 75% | 100% |
+--------------------+-------------------+--------------------+
| ACR50 | 50% | 67% |
+--------------------+-------------------+--------------------+
| ACR70 | 50% | 0% |
+--------------------+-------------------+--------------------+
| DAS28 remission | 50% | 33% |
+--------------------+-------------------+--------------------+
A magnetic resonance imaging (MRI) assessment was also included in this study.
At week 24, there was a reduction of bone oedema, which is an early indicator of
joint destruction. Additionally, the global radiographic score confirmed the
absence of disease progression at this final time point.
Dr Josefin-Beate Holz, Chief Medical Officer of Ablynx, commented:
"We are very pleased with the 24 week results of this Phase II part of the
study. We believe we have shown impressive clinical activity for ALX-0061 at the
predicted dose levels as well as the potential for dosing every four or every
eight weeks. The side effect profile of the Nanobody did not change over time or
with dose escalation and the therapeutic effect improved even further with
treatment duration. The majority of patients achieved a durable status of
disease remission, some of them already after the first month of treatment. In
addition, patients who had an inadequate response could be identified early on
in the treatment schedule and could even be 'rescued'. These findings confirm
the potential for ALX-0061 and the drug could become an important addition to
clinicians' range of tools to treat this severely debilitating disease."
Dr Edwin Moses, Chairman and CEO of Ablynx added:
"We believe that these new data provide additional confidence that ALX-0061
could become a very valuable treatment option for patients with RA. We are now
investigating the various possibilities through which we can progress the
development of ALX-0061, including discussions with potential partners and other
paths which will allow us to maximise the value of this asset."
Conference call and webcast presentation
The Ablynx management team will host a conference call and webcast during which
the Phase II results at week 24 will be presented, followed by a Q&A session.
This event will be held today, 13 February 2013 at 4.00 pm CET/ 10 am EST. The
conference call will be webcast live and may be accessed on the home page of the
Ablynx website at www.ablynx.com or by clicking here. If you would like to
participate in the Q&A, please dial +32 (0)2 620 0138. Shortly after the call, a
replay of the webcast and the presentation used in connection with the
conference call webcast will be available on the Company's website.
About ALX-0061 (anti-IL-6R)
ALX-0061 targets the interleukin 6 pathway via its IL-6receptor (IL-6R), which
plays a fundamental role in the inflammation process in RA.
ALX-0061 has been designed to become a best-in-class therapeutic. Its small size
(26kD) should allow ALX-0061 to penetrate more effectively into tissues. The
potent, monovalent interaction of the molecule with its target reduces the
possibility of off-target effects. Its binding to human serum albumin prolongs
the in vivo half-life of the product and can lead to improved trafficking to
areas of inflammation. The Nanobody has a very strong affinity for soluble IL-
6R which should ensure fast target engagement and could result in a fast onset
of effect. ALX-0061 appears to benefit from the general Nanobody characteristic
of having a very low immunogenic potential. ALX-0061 is a very robust and stable
drug product that is already manufactured at a multi-thousand litre scale. It
can be administered both intravenously and subcutaneously.
About Ablynx
Ablynx is a biopharmaceutical company engaged in the discovery and development
of Nanobodies(®), a novel class of therapeutic proteins based on single-domain
antibody fragments, for a range of serious human diseases, including
inflammation, haematology, oncology and pulmonary disease. Today, the Company
has approximately 25 programmes in the pipeline and five Nanobodies at clinical
development stage. Ablynx has ongoing research collaborations and significant
partnerships with major pharmaceutical companies including Boehringer Ingelheim,
Merck Serono, Novartis and Merck & Co. The Company is headquartered in Ghent,
Belgium. More information can be found on www.ablynx.com.
For more information, please contact
Ablynx:
Dr Edwin Moses
Chairman and CEO
t:Â Â +32 (0)9 262 00 07
m: +44 (0)7771 954 193 /
    +32 (0)473 39 50 68
e:Â edwin.moses@ablynx.com
Marieke Vermeersch
Associate Director Investor Relations
t:Â Â +32 (0)9 262 00 82
m: +32 (0)479 49 06 03
e:Â marieke.vermeersch@ablynx.com
Follow us on Twitter @AblynxABLX
M:Communications:
Mary-Jane Elliott, Amber Bielecka, Claire Dickinson
t:Â Â +44 207 920 2330
e:Â ablynx@mcomgroup.com
--------------------------------------------------------------------------------
[1] Q4W: every 4 weeks - Q8W: every 8 weeks
[2] DMARDs: disease modifying anti-rheumatoid arthritis drugs
[3]ACR (American College of Rheumatology) criteria measure improvement in tender
or swollen joint counts and improvement in three of five other disease-activity
measures; ACR20 measures % of patients with 20% improvement; ACR50 measures % of
patients with 50% improvement and ACR70 measures % of patients with 70%
improvement
[4] DAS28 is an RA disease activity score based on C-reactive protein (CRP),
tender and swollen joint counts of 28 defined joints and physician's global
health assessment; a total score of >5.1 is associated with high disease
activity, moderate from 3.2 to 5.1, low disease activity from 3.2 to 2.6, and
remission of disease if <2.6
[5] Boolean remission in RA is a more recent measure of disease activity and is
achieved when at any time point, a patient satisfies all of the following:
swollen and tender joint count, patient global assessment and CRP all less than
or equal to 1.
press release in pdf format:
http://hugin.info/137912/R/1677523/547097.pdf
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Source: Ablynx via Thomson Reuters ONE
[HUG#1677523]