LUND, SWEDEN--(Marketwire - March 30, 2010) - NeuroVive Pharmaceutical AB (Aktietorget: NVP)
reports that its Phase I clinical study comparing the Cremophor®-free
intravenous cyclosporine formula NeuroSTAT® to Sandimmune® Injection
met primary and secondary endpoints. Results of the study demonstrate that
NeuroSTAT® is bioequivalent to Sandimmune® Injection and is safe and
The bioequivalence, safety and tolerability study was performed by a
leading global biopharmaceutical services provider. Fifty-two healthy
volunteers were administered single intravenous doses of each of the two
cyclosporine formulations in a randomized single-blind cross-over washout
design. Rigorous statistical analysis of all 9 measured pharmacokinetic
variables including maximum concentration (Cmax), half-life and area under
the curve (AUC) established the bioequivalence of NeuroSTAT® to
Sandimmune® Injection, meeting the primary end-point.
Sandimmune® Injection subjects had an overall rate of moderate and mild
side effects significantly higher than NeuroSTAT®. NeuroSTAT® showed
only mild side-effects, which were well tolerated. The safety and
tolerability of NeuroSTAT® was established, meeting the secondary end-
One subject receiving Sandimmune® Injection developed severe anaphylactic
reaction, a potentially life-threatening condition, and another subject
receiving Sandimmune® Injection developed a moderate anaphylactic
reaction. Both subjects required acute medical treatment, in the first
case, lifesaving, by the responsible physician. A third person who received
Sandimmune® Injection experienced a moderate allergic reaction, which
also called for medical intervention. Because of these serious side effects
of Sandimmune® Injection, the authorities temporarily halted the study
and pre-medication with anti-inflammatory drugs (corticosteroids and
antihistamines) was introduced for the remainder of the study. No serious
side-effects of Neuro-STAT® were reported in the study.
While the package insert (revision October 2009: T2010-03) reports the rate
of anaphylactic reactions to Sandimmune® Injection to be 1 per 1000
patients, the observed incidence in this study (2 out of 19 non-pre-
medicated subjects receiving Sandimmune® injection) would, if reproduced
in a larger population, represent a rate of anaphylactic reaction of more
than 100 per 1000 subjects (more than 10%). The discrepancy is likely due
to the fact that these subjects were not pre-medicated with corticosteroids
as recommended for transplantation patients receiving Sandimmune®
Injection as part of an immunosuppression protocol.
The NeuroSTAT® cyclosporine lipid emulsion is designed to be especially
suitable in new indications for intravenous cyclosporine such as
neuroprotection in traumatic brain injury and cardioprotection (in cardiac
reperfusion injury) where, unlike immunosuppression, patients would not
receive corticosteroid pre-medication. The use of corticosteroids in
traumatic brain injury patients is firmly not recommended in the published
Guidelines for the Management of Severe Traumatic Brain Injury by the
American Association of Neurological Surgeons and the Brain Trauma
Eskil Elmér, NeuroVive CEO states: "The successful study results are
unreservedly positive. NeuroSTAT® is bioequivalent to Sandimmune®, yet
free from Sandimmune's risk of causing anaphylactic reactions. This is the
foundation for the use of NeuroSTAT® in clinical trials treating brain
trauma and reperfusion injury during heart attack. It also opens commercial
opportunities as a safer treatment for all existing indications where
intravenous cyclosporine is used, such as organ and bone marrow
NeuroSTAT® (ciclosporin, Ph Eur/USP, 5 mg/ml) is a patented, convenient,
ready-to-use, full strength cyclosporine lipid emulsion for intravenous
infusion. It has the following advantages over I.V. Sandimmune:
(i) Ready-to-use solution. The ready to hang and administer bottles do not
require dilution from a concentrate, reducing measuring and dosing errors
and delays when rapid drug administration is critical to patient treatment.
(ii) Physiological emulsifier. The contents of NeuroSTAT® are
physiological fats and phospholipids that can be metabolized by the human
(iii) No risk of Cremophor® EL-related severe hypersensitivity reactions,
including anaphylactic reactions.
(iv) No risk of Cremophor® EL-related cyto-, nephro- and cardiotoxicity.
(v) Eliminates need for specialized I.V. tubing required for Cremophor®
EL-containing products (to prevent leaching of plasticizers).
Cremophor® EL is a detergent-like agent used to keep lipophilic drugs in
solution. Cremophor® EL is implicated in anaphylactic reactions. For some
Cremophor®-containing intravenous drugs, like Taxol®, corticosteroids
are a required premedication to reduce risk of anaphylactic reactions.
Cremophor® is not present in newer drug formulations for this safety
reason, including the propofol intravenous anesthetic Diprivan® and the
paclitaxel intravenous chemotherapeutic agent Abraxane®. NeuroSTAT®
does not contain Cremophor® EL, while Sandimmune® Injection does.
NeuroVive Pharmaceutical AB
NeuroVive Pharmaceutical AB is a Swedish pharmaceutical company.
NeuroVive's primary mission is to bring NeuroSTAT® to clinical trials
treating brain trauma and reperfusion injury during heart attack. Further,
world-wide registration of a Cremophor® EL-free intravenous cyclosporine
lipid emulsion will provide a safer alternative to transplantation
In its neuroprotection program, in addition to introducing NeuroSTAT® as
the first cyclophilin-D-inhibiting mitochondrial protectant, NeuroVive is
researching immunosuppressive and non-immunosuppressive cyclosporine
derivatives and new ways of transporting these drugs across the blood-brain
NeuroVive is now identifying commercial partners for generic indications
and development partners for neuroprotection and cardioprotection.
NeuroVive Pharmaceutical is listed on the Swedish equity marketplace
AktieTorget (www.aktietorget.se). Trading is executed in the electronic
trading system used by NASDAQ OMX (the Stockholm Stock Exchange) called
NeuroVive Pharmaceutical AB (publ), Biomedical Center D10, SE-22184 Lund,
Sweden, Tel. + 46 46 288 0110, Fax. + 46 46 888 8348, Cell. + 46 733
919601, Skype neurovive, E-mail firstname.lastname@example.org,
Abraxane® is a registered trademark of Abraxis Bioscience, LLC.
Cremophor® is a registered trademark of BASF AG.
Diprivan® is a registered trademark of AstraZeneca.
Sandimmune® is a registered trademark of Novartis International AG.
Taxol® is a registered trademark of Bristol-Myers Squibb.
Press Release (PDF): http://hugin.info/139945/R/1399202/354753.pdf