Injectable peptide rapidly reduces intracranial pressure

Patients with idiopathic intercranial hypertension (IIH) could be treated with an injectable peptide used for type 2 diabetes, a Phase II trial has found. According to the study results, brain pressure was significantly reduced within two and half hours after an injection of exenatide, a GLP-1 receptor agonist.

IIH is a condition that raises pressure in the brain, likely due to a cerebrospinal fluid (CSF) imbalance. Weight gain is a major risk factor of developing IIH. Symptoms include chronic headaches and the condition can also lead to pressure on the optic nerve, which can result in blindness. The illness predominately affects women aged 25 to 36. Historically a rare condition, the researchers highlighted there has been a 350 per cent rise in incidence in last 10 years.

“There are no current licenced drugs to treat IIH and hence this result is a major step forward for patients,” explained Professor Alex Sinclair, Professor of Neurology in the Institute of Metabolism and Systems Research at the University of Birmingham, an Honorary Consultant Neurologist at University Hospitals Birmingham NHS Foundation Trust, and Principal Investigator of the study.

Exenatide – a GLP-1 receptor agonist

For the 16 patients in the clinical trial, the twice daily, subcutaneous injection facilitated an average of 7.7 fewer days per month of headaches compared to the baseline. This was compared to only 1.5 fewer days in the placebo arm.

The seven patients who received regular exenatide injections had a drop in brain pressure in both in the short term, 2.5hrs and 24hrs and the long term, 12-week measurements.

Results from the trial, IIH Pressure, were published in the journal Brain.

Future Phase III trials

While all female participants were able to continue exenatide with few adverse effects, the treatment caused nausea due to twice delivery of the drug via injection. Therefore, the drug has now been reformulated into Presendin. This once weekly subcutaneous injection is designed to control brain pressure within hours of administration and dosing lasting a week.

“We very much look forward to the next steps and seeing the drug tested in two large Phase III clinical trials,” Shelly Williamson, the Chair of patient charity IIH UK stated.

The IIH Advance is a Phase III clinical trial in adolescents run in the UK, sponsored by the University of Birmingham, UK. The trial will randomise patients with IIH to determine the efficacy and safety of Presendin versus placebo.

IIH EVOLVE is an international Phase III clinical trial. Run by Invex Therapeutics, it will randomise 240 adult patients with newly diagnosed IIH with papilloedema to determine the efficacy and safety of Presendin, administered once weekly over 24 weeks. The primary endpoint of IIH EVOLVE will assess efficacy of Presendin to reduce intracranial pressure (ICP) over 24 weeks compared to placebo.

Sharing with EPR, the researchers concluded: “This is an exciting time as we may see the first licenced treatment option coming though for a patient group in great need.”