Spinifex Announces Positive Phase 2 Results for EMA401 in Postherpetic Neuralgia
MELBOURNE, Australia, August 28, 2012/PRNewswire/ --
Trial Meets Primary Endpoint: Reduction in Pain
Spinifex Pharmaceuticals, an Australian pain drug development
company, today announces positive headline results from the Phase 2
clinical trial of its lead product, EMA401, in postherpetic
neuralgia (PHN), a painful condition that develops in some patients
following herpes zoster (shingles) and where existing therapy does
not relieve pain in all individuals.
The clinical trial met its primary endpoint, reduction in mean
daily pain score versus placebo over the last week of 28 days of
treatment. Results show a statistically significant and clinically
meaningful reduction in mean pain intensity from baseline to week 4
for subjects on active treatment when compared to placebo. On an
intent to treat basis, the mean pain intensity reduction from
baseline after 4 weeks treatment was as follows: EMA401: -2.34;
Placebo: -1.64; p = 0.006.
A significantly greater proportion of patients on active treatment
reported a more than 30% reduction in mean pain intensity score
compared to baseline (i.e. responder rate) (EMA401: 56.5%; Placebo:
34.1%; p = 0.003), meeting a key secondary endpoint.
EMA401 was generally safe and well tolerated with no serious
treatment related adverse events reported.
The double-blind, placebo-controlled randomised trial was recruited
at 29 centres in six countries and enrolled 183 patients. More
details on the trial design and results can be found in the
appendix.
Spinifex will be presenting an overview of the clinical development
of EMA401 today at the 14th World Congress of Pain(R) in Milan, a
major international meeting organised by the International
Association for the Study of Pain (IASP(R)). Full results of the
Phase 2 trial are expected to be published in a leading pain
clinical research journal.
Dr Milton Raff (Christiaan Barnard Memorial Hospital, Cape Town,
South Africa), Principal Investigator for the Study, said: "These
headline results are very promising with a clear reduction in pain
versus placebo and a good safety and tolerability profile. EMA401
offers an entirely novel approach to the treatment of PHN and could
represent a valuable new option in an area where there is a clear
need for new medicines. Current treatments for the condition are
effective in some patients but a significant proportion either
don't respond to therapy and are left with debilitating symptoms or
suffer significant side effects."
Spinifex Pharmaceuticals CEO Tom McCarthy said: "Today's results
are a major step for Spinifex and for the development of EMA401 as
a treatment for neuropathic pain. It is tremendously gratifying for
the Spinifex team to have taken a scientific discovery through to
proof of clinical concept in what is a notoriously difficult field
and one where new treatments are clearly needed. We look forward to
advancing EMA401 further in PHN and other neuropathic pain
indications including cancer chemotherapy induced neuropathic pain
and painful diabetic neuropathy. Ultimately we hope EMA401 becomes
a broad treatment for chronic pain in general."
The market for neuropathic pain treatments is expected to continue
to increase and is projected to reach US$6.2 billion by 2017.
Despite this growth, current therapy needs to be improved as a
significant proportion of neuropathic pain patients don't respond
to current therapy and these treatments have dose-limiting side
effects. As a result, EMA401 is being developed as a potential
first-in-class oral treatment for neuropathic pain and related
symptoms without central nervous system side effects. In addition
to PHN, Spinifex's clinical program for EMA401 includes a Phase 2
study in the treatment of neuropathic pain in cancer chemotherapy
patients and this trial is currently recruiting.
EMA401 is an angiotensin II type 2 (AT2) receptor antagonist. The
discovery that AT2 receptor antagonists offer an innovative
approach to the treatment of neuropathic and inflammatory pain was
originally made by Professor Maree Smith at The University of
Queensland. Having acquired the technology, Spinifex has conducted
a comprehensive pre-clinical and early clinical development program
on EMA401. In addition to positive Phase 2 results, EMA401 has
shown efficacy in a number of relevant pre-clinical models and good
human safety and pharmacokinetics in Phase 1 studies. Spinifex
continues to conduct research into the role of the AT2 receptor in
nociceptive, inflammatory and neuropathic pain states and these
fundamental studies support not only the EMA401 clinical program
but also Spinifex's ongoing AT2 receptor antagonist drug discovery
program.
Spinifex Pharmaceuticals
Spinifex Pharmaceuticals is an Australian biotechnology company
developing new drug candidates for the treatment and management of
pain.
Established in 2005 and based in Melbourne, Spinifex has applied
its world-class drug development capabilities to advance product
candidates. Its lead product EMA401 is under development as a
potential first-in-class oral treatment for neuropathic pain and
related symptoms without CNS side effects. Spinifex's Phase 2
program for EMA401 includes clinical trials in a number of
neuropathic pain conditions. Spinifex investors are GBS Venture
Partners, Brandon Capital Partners, Uniseed and UniQuest.
http://www.spinifexpharma.com.au
APPENDIX - CLINICAL TRIAL RESULTS SUMMARY
Official Title:
A double-blind, placebo-controlled, randomised trial to prove the
therapeutic concept and to determine the safety, tolerability,
pharmacokinetic profile and efficacy of EMA401 (angiotensin II type
2 receptor antagonist) administered orally in patients with
postherpetic neuralgia.
Identifying Codes:
Protocol No. EMA401-003
Primary Objective:
To determine the efficacy of EMA401 when administered orally, twice
daily (100 mg b.i.d.), in patients with postherpetic neuralgia, as
assessed by difference in mean pain intensity score compared to
placebo.
Primary Endpoint:
Change in mean pain intensity score (using the 11-point numerical
rating scale/Likert scale) between baseline and the last week of
dosing (Day 22 to 28).
Study Design:
This study was a randomised, double blind, placebo controlled,
parallel-group Phase 2 proof of concept efficacy clinical trial.
Patients were randomised to receive either 100mg EMA401 or placebo
twice daily orally for 28 consecutive days with a final dose on the
morning of Day 29 for pharmacokinetic evaluation.
183 patients were enrolled and randomised to receive EMA401 (92
patients) or placebo (91 patients) and this constitutes the intent
to treat population. The per protocol population consisted of 158
patients (79 in the EMA401 treatment group and 79 in the placebo
group).
Patients attended the study centre weekly for on-study assessments
on Days 8, 15, 22 and 29. During the Treatment Period, study
medication (EMA401 or placebo) was self-administered at home by the
patient except on the study visit Days 1, 8, 15, 22 and 29 where
the morning dose of the study medication was self-administered at
the study centre. Patients underwent a follow-up assessment on Day
42.
Sites:
The study was recruited across 29 sites in Bulgaria, the Czech
Republic, Georgia, Serbia, South Africa and Ukraine. Randomisation
to EMA401 and placebo was balanced across all six countries.
Key Inclusion Criteria:
1. Be able to give voluntary written informed consent to
participate in the study.
2. Be over 18 years of age.
3. Be diagnosed as suffering from PHN defined as pain persisting
for more than six months after onset of herpes zoster rash.
4. Be diagnosed as suffering from moderate to severe pain across
the Screening Period.
5. Willing and able to comply with all study procedures.
6. For females, have a negative pregnancy test at the Screening
visit (Visit 1) and at Visit 2 (Day 1) prior to administration of
study medication.
7. For females, be of non-child-bearing potential (i.e. either
surgically sterilised or one year post-menopausal), or if of
child-bearing potential, must have used adequate contraceptive
precautions for 30 days prior to Screening, and must agree to use
two approved methods of contraception for the duration of the
study, and for one month after administration of the last dose of
study medication.
For males: Agrees to use two approved methods of contraception for
the duration of the study and until one month after administration
of the last dose of the study medication.
8. Be fluent in the language of the endpoint scales provided to
patients in the study.
RESULTS
Patient Demographics:
A summary of the demographics and baseline characteristics is
presented in the Table below.
Description EMA401 Placebo Total
Total Patients (Intent to Treat) 92 91 183
Total Patients Completing Treatment
Period (Day 29) 87 84 171
Total Completing Follow Up
Assessment (Day 42) 86 83 169
Age [Mean (SD)] in years 62.5 (14.9) 63.4 (14.4) 62.9 (14.6)
Age (min.- max.) in years 22-86 27-89 22-89
Weight [Mean (SD)] in kg 78.5 (13.3) 76.4 (15.9) 77.4 (14.6)
Gender - Male 43 40 83
Gender - Female 49 51 100
Total Patients (Per Protocol) 79 79 158
Conmeds:
Patients were allowed to continue taking only one approved
neuropathic pain treatment however they still had moderate to
severe pain at study entry.
Efficacy: Primary Endpoint
The primary efficacy endpoint for this trial was met. Results show
a statistically significant reduction in mean pain intensity from
baseline to Week 4 for subjects on active treatment when compared
to placebo.
On an intent to treat basis, the mean pain intensity reduction from
baseline after 4 weeks treatment was as follows:
Placebo: -1.64
EMA401: -2.34
p = 0.006
For graph of mean pain intensity vs treatment time see release at
http://www.spinifexpharma.com.au
Efficacy: Secondary Endpoints
Two secondary efficacy endpoints were included.
1. Proportion of patients achieving a greater than or equal to 30%
reduction in mean pain intensity score compared to baseline (i.e.
responder rate).
On an intent to treat basis, this secondary endpoint was met:
Placebo: 34.1%
EMA401: 56.5%
p = 0.003
2. Onset and maintenance of effect as defined by pattern of change
in the mean pain intensity score over the entire Treatment
Period.
Statistical analysis is on-going.
Safety and Tolerability:
Description EMA401 Placebo Total
Number of Treatment-Emergent AE
(TEAE) 56 (60.9) 45 (49.5) 101 (55.2)
Subjects with TEAE 32 (34.8) 29 (31.9) 61 (33.3)
Subjects with TEAE Leading to Early
Termination 1 (1.1) 3 (3.3) 4 (2.2)
Subjects with Serious TEAE* 1 (1.1) 2 ( 2.2) 3 (1.6)
Subjects with Drug-related TEAE 13 (14.1) 10 ( 11.0) 23
(12.6)
Subjects with Severe TEAE 0 (0.0) 1 (1.1) 1 (0.5)
Subjects with Life-threatening TEAE 0 0 0
Death 0 0 0
*The only serious treatment emergent adverse event in the EMA401
group was deemed not to be related to study treatment.
For more information please contact:
Company
Dr Tom McCarthy
CEO Spinifex Pharmaceuticals
Tel: +61(0)3-9938-1205
Email: tom.mccarthy@spinifexpharma.com.au
Media
Chris Gardner/Nina Enegren
Citigate Dewe Rogerson
Tel: +44(0)20-7638-9571
Email: nina.enegren@citigatedr.co.uk
Source: Spinifex Pharmaceuticals
Posted: August 2012
