some results if bio r reopren

Solagran Limited
Solagran Limited
ACN 002 592 396
Level 11
492 St Kilda Road
Melbourne 3004
Victoria
Australia
Tel 61 3 9820 2699
Fax 61 3 9820 3155
10 March, 2005
Company Announcement
Detailed Phase II Clinical Trials Results Exceed Expectations
The Directors of Solagran Limited are pleased to announce that the Company has received
the final report on the results of the Phase II clinical trials of Bioeffective R in the treatment of
chronic liver disease that were completed in late 2004.
The Directors consider the trials results to be extremely positive. The final report from the
Medical Academy of Postgraduate Studies in St Petersburg (MAPS), which was compiled by
Professor Inna Gavrisheva, the clinical trials coordinator (Dr Med. Sci, Head of MAPS
Postgraduate, Doctoral and Scientific Programs and Member of Committee on Issues in
Preclinical and Clinical Trials of Pharmaceuticals at the Federal Inspectorate of Healthcare
and Social Development), and issued under the authority of Professor Tatiana Trofimova
(Vice Chancellor for Science and Publishing at MAPS) confirms all of the initial findings
which were announced to the market on 16 November, 2004. It also opens up the possibility
of Bioeffective R being used for a range of other therapeutic applications and suggests that
trials be undertaken to confirm this potential.
The final MAPS report concludes that Ropren (the finished form pharmaceutical containing
Bioeffective R) is both safe and effective, and recommends that Ropren be registered as an
active hepatoprotector for prevention and treatment of chronic hepatobiliary system disease.
The results of these clinical trials, together with the recommendations from MAPS, will now
be submitted to the Russian Ministry of Health and the Russian Pharmacopoeial Committee
as part of the process of registering Ropren and gaining entry into the Russian
Pharmacopoeia. Subject to acceptance and approval by the Russian Ministry of Health,
Solagran will be in a position to generate a revenue stream from sales of Ropren in Russia
as a hepatoprotector before the end of 2005.
The recommendation to move forward with the use of Ropren in clinical practice to treat
chronic liver disease was based in part on the results of a much wider range of pre-clinical
and pilot trials undertaken with Bioeffective R. Some of the results from these trials have
been reported to the market previously. Other trials have been conducted in St Petersburg in
conjunction with the Phase II clinical trials.
Earlier preclinical and pilot clinical trials established that Bioeffective R is practically nontoxic,
does not cause any pathological changes in biochemical indices, and does not have
any negative effects on main physiological systems or internal organs. The finished form
does not have any irritant or allergenic properties. Study of specific activity demonstrated that
the drug has an expressed hepatoprotective effect, normalises the condition of hepatic
parenchyma, increases haemoglobin levels, normalises lipid metabolism and has
immunomodulating properties.
The recent trials confirmed the clinical and laboratory efficacy and safety of Ropren in the
treatment of liver damage. Efficacy was demonstrated through improvement in general
condition, improved mood and appetite, normalisation of liver-related blood parameters -
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alanine aminotransferase (ALT), asparagine aminotransferase (AST), bilirubin and protein
fractions, a reduction in the size of the disease-enlarged liver and an increase in
haemoglobin and erythrocyte counts.
The final report also revealed a number of quite remarkable new findings relating to the effect
of Ropren on liver function and blood sugar metabolism, as well as uncovering significant
antioxidant and adaptogenic properties. These findings are summarised below.
Liver Function
Analysis of enzyme content in blood plasma (which characterises hepatocyte function)
showed highly elevated levels of ALT and AST before beginning of treatment. After
completion of the 12 week treatment course, this index returned to normal levels in patients
treated with both Ropren and the comparator. However, positive changes in ALT levels were
noted after 4 weeks in the group treated with Ropren, versus 8 weeks for the comparator
group. Changes in AST activity were of a similar nature, being evident after 6 weeks of
treatment with Ropren, compared with 8 weeks for the comparator group.
Changes in gamma glutamyl transferase or GGT (a microsomal enzyme that is elevated in
70-80% of alcohol abusing patients and those with hepatobiliary disease) were clearly
evident. Before treatment, the average level of this parameter in patients involved in the trial
was 7.4 times the normal upper limit. Over the 12 weeks of treatment, GGT gradually
returned to normal levels.
Blood Sugar Metabolism
Before the start of treatment, fasting blood serum glucose levels in both groups exceeded the
upper normal limit by an average of 11%. For patients treated with Ropren, normalisation of
this indicator of carbohydrate metabolism was noted at practically all treatment stages. After
both the 8th week and the 12th week, there was a statistically significant difference from the
initial values. In the comparator group, the difference from the initial level was not statistically
significant. At the same time, no changes in blood protein fractions were noted, confirming
the safety of application of Ropren.
Before the start of treatment, analysis of blood lipids in both groups showed
dislipoproteinemia (imbalance in cholesterol levels). The total cholesterol content exceeded
the normal upper limit by 9% on average in the experimental group and by 5% in the
comparator group. After 12 weeks of treatment, this parameter of lipid metabolism was
normalised in both groups. The same trend was observed for extremely low density
cholesterol.
As early as 6 weeks after beginning of treatment with Ropren, an increase in high density
cholesterol content was evident in the experimental group when compared with both initial
values and those from the comparator group – an extremely interesting and important
finding.
Study of changes in triglycerides content in blood serum conducted over the 12 weeks of the
trial did not show any pathological changes (either before or after treatment with Ropren and
the comparator) indicating that Ropren does not impact triglyceride synthesis or
biodistribution.
A reduction in the Atherogenic Coefficient (AC, an index for estimating the risk of developing
atherosclerosis) from 3.6 before the trials to 2.2 in the experimental group and 3.2 in the
comparator group after 4 weeks was statistically significant (*ð<0.05) – as illustrated in Table
1.
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Table 1 – Changes in Atherogenic