Evolva reports additional Phase IIa data on EV-077
Reinach, Switzerland, 28 August 2012 - Evolva Holding SA (SIX:
EVE) today announces further data for the first 32 patients
enrolled in the Phase IIa study of its investigational drug,
EV-077, a novel, reversible antagonist of isoprostanes and
prostanoids. 16 patients received EV-077 and 16 patients received
placebo.
The data indicate that 300mg EV-077 given orally twice daily to
patients with type 2 diabetes provided anti-platelet activity,
reduced exercise-induced proteinuria and increased forearm blood
flow. This was achieved with only a slight increase in bleeding
time. The analysis also indicates that EV-077 was generally well
tolerated, with adverse events mostly limited to increases in liver
enzymes, which were transient or resolved after
discontinuation.
Key Highlights of the Data
Efficacy
Platelet Aggregation
EV-077 achieved a consistent, substantial, inhibition of platelet
aggregation induced by arachidonic acid and U-46619 (measured in
whole blood and in platelet-rich plasma). This occurred at all time
points. This was the primary efficacy parameter of the study and
statistical significance was achieved (p=0.001).
Peripheral Blood Flow
Though not powered to reach statistical significance and against a
background of high variation, EV-077 shows a consistent trend to
improvement of vascular endothelial function (both macrovascular
and microvascular) after 4 weeks of treatment on top of
anti-hypertensive therapy.
Change on day 29 versus baseline EV-077 Placebo
Macrovascular endothelial function +43% +20%
Microvascular endothelial function +108% +25%
Vascular endothelial dysfunction precedes atherosclerosis and is a
common feature of diabetes. Impaired post-occlusive reactive
hyperaemia (PORH) is an accepted indicator of vascular endothelial
function. In this study PORH was investigated by flow-mediated
dilatation of the brachial artery (macrovascular) and by forearm
skin dilatation (microvascular).
Exercise Induced Proteinuria
Though not powered to reach statistical significance and against a
background of high variation, EV-077 shows a consistent trend to
improvement (a decrease) in the level of protein in the urine after
exercise.
Change on day 29 versus baseline EV-077 Placebo
Peak albuminuria – all patients -34% +12%
Peak albuminuria – exercise completers *) -54% +10%
*) not all individuals completed the exercise test, and such
individuals would not be expected to show a full response (EV-077,
baseline n=12, day 29 n= 10; placebo, baseline n= 13, day 29
n=11)
Exercise induced proteinuria is an early marker of loss of kidney
function, which is one of the most important complications of
diabetes from both a medical and an economic standpoint.
Safety
Bleeding Time Increases
Bleeding time increased from 4.4 minutes at baseline to 8.6 minutes
on day 29 for patients receiving study drug, compared with an
increase from 4.9 minutes to 5.9 minutes in the placebo arm. The
increase measured for EV-077 is not considered to be clinically
relevant and is similar or lower than that of several marketed
drugs for chronic use (notably aspirin and clopidogrel).
Adverse Events
EV-077 was generally well-tolerated; no serious adverse events
occurred in the study. Mild-to-moderate adverse events were largely
limited to increases in transaminases (liver enzymes), which were
transient or resolved after discontinuation.
Adverse Events EV-077 Placebo
Serious adverse events 0 0
Patients reporting one or more adverse events 10 6
Transaminase increase 4 0
Of the four cases of transaminase increase three were increases of
less than 3x the upper limit of normal. These either resolved
whilst remaining on EV-077 (one case) or occurred on the last day
of treatment (two cases) and resolved after the study. In one case
the increase was more than 8x the upper limit of normal, and the
patient was withdrawn from the study. This case also resolved after
discontinuation.
As stated in the media release of 17 August 2012, Evolva is
exploring, in consultation with the German regulatory authority
BfArM, how to best address the liver enzyme elevations, for example
by using lower doses in a next group of patients.
An analysis of pharmacokinetic and pharmacodynamic data support the
hypothesis that substantially lower doses (10-30mg) of EV-077 will
also demonstrate efficacy. Contrary to the media release of 17
August the data was not presented at a satellite symposium of the
ESC Congress 2012, as in consultation with the two co-chairs of the
symposium it was decided that discussions with the BfArM should
take precedence.
Norbert Bender, CMO of Evolva commented, “We believe the data
underpin the potential of EV-077 as a potentially valuable tool in
the prevention and treatment of important vascular complications in
patients with type 2 diabetes. We are looking forward to discussing
the next steps with the German regulatory authority."
- ends -
About the Phase IIa study
The Phase IIa study is designed to assess to safety, tolerability
and pharmacokinetics of 28 days EV-077 treatment (300mg, given
orally, twice-daily), and its effects on platelet function,
vascular inflammation and oxidative stress in type 2 diabetics. It
is a single-centre study, conducted in Germany. The study is
randomised, double-blind and placebo-controlled. Measurements
include oxidative stress, vascular inflammation, blood flow and
platelet reactivity, as well as markers of the function of organs
that are often impaired in diabetes (e.g. kidney).
About Evolva
Evolva’s mission is to discover and provide innovative,
sustainable ingredients for health, nutrition and wellness. Evolva
uses biosynthetic and evolutionary technologies to create and
optimise small molecule compounds and their production routes. We
are active in consumer healthcare and nutrition as well as in
pharma. In both areas we have partnered projects as well as
proprietary programmes. For more information see
www.evolva.com.
Contact Details
Neil Goldsmith, CEO Jakob Dynnes Hansen, CFO Paul Verbraeken,
IR
neilg@evolva.com
jakobdh@evolva.com
paulv@evolva.com
+ 41 61 485 2005 + 41 61 485 2034 + 41 61 485 2035
This press release contains specific forward-looking statements,
e.g. statements including terms like believe, assume, expect or
similar expressions. Such forward-looking statements are subject to
known and unknown risks, uncertainties and other factors which may
result in a substantial divergence between the actual results,
financial situation, development or performance of the company and
those explicitly or implicitly presumed in these statements.
Against the background of these uncertainties readers should not
place undue reliance on forward-looking statements. The company
assumes no responsibility to update forward-looking statements or
to adapt them to future events or developments.
Posted: August 2012
