After obtaining all regulatory and ethics committee approvals, the first study centre has been initiated in Austria. Centres in Germany, Belgium, Spain, the Czech Republic, Slovakia and Sweden are planned to follow shortly. Overall about 65 centres are planned to take part in the AXIS 2 study. Enrolment is scheduled to take approximately 18 months and the first results are expected about 6 months thereafter.
The randomized, double-blind trial will enrol 350 patients assigned to two groups, one AX200 group and one placebo group, with 175 patients each. The goal of AXIS 2 is to assess the efficacy of AX200 compared to placebo in patients suffering from acute ischemic stroke. Patients will be enrolled up to nine hours after occurrence of an ischemic stroke and treatment will be administered as an infusion for 3 days.
The primary endpoint of the AXIS 2 trial is patient outcome evaluated using the modified Rankin Scale (mRS) which is the universal standard clinical scale for measuring global functioning of stroke patients. Secondary endpoints include further clinical scales for functional ability on one hand, and safety as well as imaging technology to assess changes in infarct size on the other hand.
Dr. Frank Rathgeb, SYGNIS CMO, commented:
“In our previous trials AX200 showed a very favourable safety profile as well as initial hints of efficacy. In preclinical tests we were able to demonstrate that AX200 has multifunctional beneficial activities, which limit the damage of stroke and support the recovery of the diseased brain. Thus the compound has the potential to be a very effective treatment for millions of stroke patients globally. It is a major milestone for SYGNIS to be entering the next stage within the development of our lead candidate, AX200, and to further increase the value of our proprietary portfolio.”
About AX200
AX200 is developed by SYGNIS for the treatment of neurodegenerative diseases. It is the most advanced drug candidate in SYGNIS’ product pipeline. SYGNIS successfully completed a clinical phase IIa trial in 44 patients (AXIS 1) that demonstrated that AX200 was safe and well tolerated. The results were very encouraging as explorative analyses revealed a beneficial, dose-related effect of AX200 on functional outcome in patients with medium and large infarct size. AX200 is an endogenous protein (G-CSF). As part of the body's own protective action the production of AX200 is boosted after brain damage.
AX200 acts on multiple mechanisms in stroke pathophysiology: AX200 protects neurons from cell death in the acute phase of the disease while at the same time stimulating the regeneration of the already damaged brain through the stimulation of neurogenesis as well as arteriogenesis and the reorganisation of neuronal networks. Following the granting of the corresponding European patent in 2006, the USPTO issued the patent in March 2009 which protects the use of AX200 for the treatment of stroke patients with AX200 in the USA.
About Stroke
Stroke is a severe disease which is characterised by sudden onset and followed frequently by death or prolonged disabilities of the patients. With 1.8 million new stroke patients every year, and 200,000 new patients in Germany alone, stroke is ranked number three as cause of death in the industrialized nations, and is one of Europe's major causes for disabilities and invalidity. The most common form of stroke is brain ischemia (85 percent). It is caused when the blood supply of the brain is disrupted by a thromboembolic event, followed by oxygen and glucose deprivation of the affected brain area. Following the reduced blood supply, massive neuronal cell death occurs and inflammatory and edematous processes are activated, which further increase the lesion and the infarct area. The patients suffer mostly from motor impairment such as weakness of the limb or paralysis, but also from speech and visual disorders. Besides the ischemic stroke which is caused by the obstruction of a blood vessel, hemorrhagic stroke is a second form of stroke caused by a bleeding into the brain parenchyma. General risk factors for stroke are old age, elevated blood pressure, smoking, reduced physical activity, increased body weight, diabetes, and elevated levels of lipids in the blood.
Currently, only one pharmacological therapy is approved for the treatment of acute ischemic stroke in the US and in Europe: lysis of the blood clot obstructing the vessel by tissue plasminogen activator (t-PA). A drawback of the currently approved lysis therapy is that it is only approved for treatment within three hours after the onset of symptoms. Combined with the extensive diagnostic proceedings necessary to diagnose stroke and to exclude other reasons of disease, only three to five percent of stroke patients receive lysis therapy.
About SYGNIS Pharma
SYGNIS Pharma AG, headquartered in Heidelberg, is a specialty pharmaceutical company listed on the Prime Standard of the German stock exchange. The Company is focused on the research, development and marketing of innovative therapies for the treatment of disorders of the Central Nervous System. These include Stroke, Amyotrophic Lateral Sclerosis and neurological disorders resulting from injuries to the brain or spinal cord. All these disorders are characterized by the fact that, as the disease progresses, nerve cells are damaged and die. Although there is great medical demand, there are currently no or only inadequate treatment options available.
One of SYGNIS’ central elements in this value-creation chain is the continued development of the existing product pipeline. This is achieved by testing the Company’s proprietary compounds which are already under development in a number of further CNS indications (“line extension”). By means of specific R&D programs at SYGNIS, new pre-clinical drug candidates are identified and evaluated as well as early-stage projects initiated for the purpose of partnering.
