CLINUVEL PHARMACEUTICALS LTD announced that it is evaluating the effects of its drug afamelanotide in patients suffering from arterial ischaemic stroke (AIS) in a pilot study (CUV801). Ischaemic stroke patients suffer a life-threatening condition when a blood clot blocks an artery depriving the brain of blood and oxygen. Afamelanotide will be administered to six AIS patients to evaluate its safety and effectiveness. Stroke patients suffer an acute and life-threatening condition when a clot in a major brain vessel blocks blood flow and oxygen, causing instant death of brain tissue. Stroke is often characterised by a patient's sudden impairment of consciousness, inability to move one side of the body and limitation of speech. Ischaemic stroke accounts for approximately 85% of the estimated 15 million global stroke cases reported annually. In AIS, the centre of the brain injury is called the necrotic core (dead brain tissue), and the larger surrounding brain injury is characterised as the penumbra (literally: shadow around the core). The necrotic core is brain tissue beyond rescue, whereas the penumbra is the part of the brain deprived of oxygen but still salvageable if immediate therapy is administered to the stroke patient. The current standard therapy relies on early intervention following stroke onset to restore blood flow to the brain by either chemically dissolving or physically removing the clot. Globally, intravenous thrombolytic therapy (IVT) in the form of recombinant tissue plasminogen activator (alteplase or tenecteplase; rt-PA) is administered within 4.5 hours, aiming to dissolve the clot within the brain artery. Estimates vary, but 7-21% of patients presenting to hospital within the therapeutic window receive IVT.3,4 This therapy is usually combined with endovascular thrombectomy (EVT) which aims to mechanically remove the clot, preferably performed within 24 hours of the stroke. EVT is a relatively new procedure, only 11% of US stroke patients are considered eligible and approximately 12% of AIS patients receive this therapy in Europe.3,5 Brain imaging, using a computed tomography (CT) scan, is performed upon hospital admission for patients with symptoms of brain injury.6 Physician assessment of the loss of neurological functions is made using the modified Rankin Scale (mRS), a scoring of severity of disability. In Europe, over 85% of AIS cases presenting to hospitals are not eligible for current standard of care treatment. The location of the brain clot has a direct impact upon the possibility to offer the combined therapy (IVT) and EVT treatment, as well as overall patient prognosis.Clots in the main"M1" segment of the middle cerebral artery (MCA) are generally eligible for IVT or EVT due to the diameter of the artery and the ability to physically remove the clot,whereas those in smaller arteries are considered impossible to remove or of too great a risk to the patient. Relevant to planned AIS treatment, afamelanotide is shown to exhibit neuroprotective, vasoactive (acting on blood vessels), anti-oncotic (anti-swelling) and anti-oxidative effects by optimising blood flow, and reducing the size of an injury and fluid (oedema) formation. Afamelanotide will be administered to those AIS patients who are ineligible to receive standard therapy (IVT/EVT), and in stroke affecting the M2 segment or higher, where there is a great unmet medical need. The first pilot Phase IIa study (CUV801) of its kind will evaluate SCENESSE® (afamelanotide 16mg) in six AIS patients. CUV801 will be conducted over the course of six weeks, at a single expert neurological emergency centre, whereby assessments will be made of the brain injury through MRI scans and according to overall disability (neurological assessment, NIHSS7 and mRS8). The primary study objective is to assess the safety of SCENESSE®, while the secondary objective is to assess whether the therapy affects the size of the penumbra, by increasing blood flow, restoring oxygen supply to the brain, and reducing the amount of cerebral oedema (fluid) which is seen as a result of the stroke. Positive findings would indicate that the drug is able to support brain tissue-at-risk and provide overall neuroprotection and benefit to stroke patients. CUV801 will commence recruitment once COVID restrictions on available medical staff have eased. Afamelanotide, the active ingredient in SCENESSE® is a tridecapeptide, an analogue of the naturally occurring alpha- melanocyte stimulating hormone and belongs to the group of proopiomelanocortins (POMC). As scientifically reported, afamelanotide exerts a number of pharmacological effects which may be of clinical benefit to patients with acute and life-threatening disorders. More than 10,000 doses of afamelanotide have been administered to over 1,400 individuals during its development and use across a period of nearly two decades. The safety profile of afamelanotide as a controlled-release injectable implant formulation (SCENESSE®) has been shown to be consistently positive. SCENESSE® is currently approved in Europe, the USA and Australia for adult patients with the rare genetic disorder erythropoietic protoporphyria. Globally, 15 million patients suffer from a stroke annually, and over 5.5 million do not survive.2 Around 40% of AIS patients do not survive the first year, with as many as 50% of stroke survivors suffering permanent disability. A quarter of stroke patients will experience a second stroke within five years, with 12% of AIS patients being readmitted to hospital within 30 days of discharge. Most patients require ongoing care and unfortunately suffer limitations in their daily social activity and productivity. Families often have to shoulder excessive rehabilitation costs and lost wages. In the United States alone, recent estimates place the cost of stroke in excess of $34 billion per year.