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Spinifex Pharmaceuticals Pty Limited Announces Positive Phase 2 Results for EMA401 in Postherpetic Neuralgia



8/28/2012 10:05:18 AM

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® in Milan, a major international meeting organised by the International Association for the Study of Pain (IASP®). 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 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


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