STOCKHOLM, Aug. 28, 2019 /PRNewswire/ -- IRLAB
(Nasdaq First North Premier: IRLAB A) today announced that the
in-depth analysis of the data from the recently concluded Phase IIa
study of IRL790 in Parkinson's patients with L-dopa induced
dyskinesia (LIDs) brings further evidence of the drug candidate's
ability to significantly and meaningfully improve daytime movement
quality. IRLAB has therefore decided to prioritize the LIDs
indication in the development of IRL790. A Phase IIb/III study in
this patient group is planned to start in the first half of 2020,
as part of a pivotal clinical program towards market approval. The
planned study in Parkinson's disease psychosis will be performed in
parallel with the pivotal program in LIDs.
The in-depth data analysis is based on data from the recently
concluded Phase IIa study to evaluate the efficacy, safety and
tolerability of IRL790 in patients with L-dopa induced dyskinesias
(LIDs, involuntary movements). Three independent measurement
methods were used to assess the clinical efficacy of IRL790:
UDysRS, MDS-UPDRS and standardized patient reported
diaries. As previously communicated, IRL790 showed
beneficial safety, tolerability and pharmacokinetics in the study.
Two out of three measurement methods revealed a significant and
clinically meaningful effect on dyskinesia.
"I think that the study shows a strong efficacy signal for
IRL790 in treating dyskinesia in people with Parkinson's, using
measures that are of relevance to them, and importantly with very
few adverse events. These findings need to lead to larger studies,
to more clearly evaluate the efficacy, and hopefully lead to a
much-needed additional therapy for this disabling side-effect of
levodopa therapy", said Dr Camille
Carroll, Associate Professor and Honorary Consultant
Neurologist and National Speciality Lead for Neurodegenerative
Diseases NIHR CRN, University of Plymouth.
"IRLAB has now concluded an in-depth analysis of the Phase IIa
study data that further substantiates the potential for IRL790 to
improve treatment of L-dopa induced dyskinesia. We have gained a
deeper understanding of the results, including pros and cons of the
independent measurement methods used in the study, and are now able
to optimize the clinical path forward. The next step will be
initiation of a Phase IIb/III study in this severely troubled
patient group, which can be part of the pivotal program. The
planned study in Parkinson's disease psychosis will be performed in
parallel with the final studies in the LIDs program. This does not
delay the total program", said Nicholas
Waters, CEO at IRLAB.
Assessments of motor function
The in-depth analysis of study efficacy data showed clinically
meaningful effects on dyskinesias assessed by the Hauser
standardized patient reported diaries and by MDS-UPDRS (Unified
Parkinson's Disease Rating Scale) dyskinesia assessments. The
patient reported diaries showed that IRL790 treatment, compared to
placebo, significantly reduced patient's time with troublesome
dyskinesias by 1.6 hours daily. In patients without concomitant
amantadine treatment, the reduction in time with troublesome
dyskinesia was 2.7 hours daily, compared to placebo. Further,
MDS-UPDRS dyskinesia assessment showed a significant improvement in
patients treated with IRL790 as compared to placebo. As illustrated
in the data table below, both of these efficacy endpoints were
further improved over placebo in patients who were not treated with
the anti-parkinsonian drug amantadine as part of their regular
medication.
Joakim Tedroff, CMO at IRLAB, commented: "In patients with
advanced Parkinson's disease, IRL790 treatment improved the motor
function response with a marked qualitative shift in ON-time
towards more 'good ON hours', without troublesome dyskinesia
or adverse effects. This beneficial shift in motor response quality
was even more pronounced in patients not taking amantadine. This
amantadine interaction is a very important discovery from a
therapeutic perspective. In order to demonstrate the true efficacy
of IRL790 this will be considered when designing coming clinical
studies."The period when levodopa has a positive effect on
Parkinson's disease symptoms is called ON-time and is also when
dyskinesias occur. Once the medication stops working, the so-called
OFF-time starts, where symptoms recur. In-depth assessment of other
motor symptoms of Parkinson's disease using MDS-UPDRS part II+III,
MDS-UPDRS OFF-time assessment as well as the 24-hour diaries showed
that patients treated with IRL790 maintained their general motor
function and their total daily ON-time. There was no change in
daily OFF-time. Thus, the positive effects of IRL790 are achieved
without negative effects on traditional Parkinson symptoms,
increased OFF-time or decreased ON-time. These important
observations were similar in patients with, and without concomitant
amantadine treatment.
Application of UDysRS in the study
As previously communicated in the top-line analysis, no
difference in efficacy between IRL790 and placebo was seen using
the Unified Dyskinesia Rating Scale (UDysRS), despite the
significant effects on dyskinesia in patient reported diaries and
MDS-UPDRS assessments. The objective UDysRS parts III and IV are
designed to be applied in patients in ON state, i.e. when
dyskinesias are present. In-depth analysis of the UDysRS data
generated now show that the assessments suffer from technical
shortcomings during sampling of the UDysRS since many of the
patients were not in ON state during these assessments. The
frequency of patients not in ON state indicate that UDysRS data is
not relevant for assessment of ON state dyskinesias in this
study.
Assessment of dosing and pharmacokinetic
properties
The suitable dose range for treatment of dyskinesia in
Parkinson's disease has been established in this study. Doses
ranging 10 to 20 mg/day, are safe, tolerable and effective. In
accordance with previous studies, IRL790 demonstrated linear
kinetics with dose proportional plasma concentrations, which allows
for good control of exposure. This greatly facilitates dosing in
the Parkinson's disease population. These patients, who generally
need individual dosing, will benefit from the pharmacokinetic
properties of IRL790, which allows for dosing and dose adjustments
with high precision. No influence by the patients' other treatments
on plasma concentrations of IRL790 could be detected in the
study.
Assessment of side effects
IRL790 was well tolerated and safe in the study, indicating a
superior safety and side effect profile. Any adverse event was
reported by 78 % of placebo treated patients and 74% of IRL790
treated patients. The most common adverse events reported by system
organ class (SOC) were nervous system disorders reported by 42% of
placebo treated patients and 49% of IRL790 treated patients. There
were three Serious Adverse Events (SAEs), none related to IRL790
treatment. Cardiovascular assessments including blood pressure,
heart rate, and ECG, showed no clinically relevant changes due to
IRL790 treatment.
The full results of the study will be published in an
international scientific journal.
For further information
Nicholas Waters, CEO
Phone: +46 730 75 77 01
E-mail: nicholas.waters@irlab.se
Joakim Tedroff, CMO
Phone: +46 70 760 16 91
E-mail: joakim.tedroff@irlab.se
This information was brought to you by Cision
http://news.cision.com
https://news.cision.com/irlab-therapeutics-ab/r/irlab-to-advance-clinical-development-of-irl790-in-lids-based-on-in-depth-analysis-of-positive-phase,c2889932
The following files are available for download:
https://mb.cision.com/Main/15440/2889932/1096377.pdf
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IRL790 Ph2a further
info
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https://news.cision.com/irlab-therapeutics-ab/i/table-c003,c2672080
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Table C003
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