NeuroVive Pharmaceutical AB (SE) - NeuroVive successfully completes clinical trial with Cremophor-free cyclosporine I.V. formulation
NeuroSTAT® cyclosporine I.V. meets primary and secondary endpoints, demonstrates bioequivalence and improved safety and tolerability when compared with Sandimmune® Injection.
Lund, Sweden - 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 well tolerated.
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-point.
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 Foundation.
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 transplantation."
NeuroSTAT® 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 body. (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 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 patients. 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 barrier. 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<http://www.aktietorget.se>). Trading is executed in the electronic trading system used by NASDAQ OMX (the Stockholm Stock Exchange) called INET Nordic.
For more information contact: Eskil Elmér, MD, PhD, CEO and CSO, Neurovive Pharmaceutical AB (publ) Phone: + 46 733 919601, firstname.lastname@example.org
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 email@example.com
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/1399185/354747.pdf>
Posted: March 2010