Clinical-stage biopharmaceutical company Invex Therapeutics (ASX: IXC) has received written feedback from the US Food and Drug Administration’s (FDA) Division of Neurology relating to the proposed design of a phase III clinical trial of lead drug Presendin for the treatment of idiopathic intracranial hypertension (IIH).
In March, the company submitted a study protocol and statistical analysis plan to the FDA, along with a number of questions.
The documents sought the FDA’s guidance on the overall study design, and cited intracranial pressure and headache as primary endpoints.
The FDA has since returned a set of written responses, recommending Invex consider a “clinically-meaningful effect” on visual function as an alternative primary endpoint.
It suggested perimetric mean deviation – which is a measure of change in a patient’s visual field – and was open to Invex providing proposals for how Presendin (formerly Exenatide) could improve this.
The FDA considered intracranial pressure as an appropriate secondary (not primary) endpoint of the study, which contrasts with advice that Invex has previously received from the European Medicines Agency (EMA).
Few specific comments were made relating to the planned measure of monthly headache days, however the FDA did recommend an abbreviated headache severity scale as an alternative assessment.
Potential approval pathway
Invex chairman Dr Jason Loveridge said the FDA’s feedback would further inform the company of a potential approval pathway for Presendin as a treatment for IIH in the US.
“Our clinical trial protocol and statistical analysis plan sought to harmonise and gain a broad consensus between the EMA and FDA by incorporating key endpoints which would best reflect the signature of the disease and the very broad impact of headache on patient quality of life,” he said.
“In its response, the Division of Neurology repeated the original Division of Ophthalmology feedback that visual function should be a key outcome measure of a study seeking approval of a drug for the treatment of idiopathic intracranial hypertension.”
Dr Loveridge said the company would meet with key regulatory and clinical advisors in the coming weeks to better understand the FDA responses and determine the best direction and design for the study.
Raised pressure levels
IIH is characterised by severely raised pressure levels within the skull which can cause signs and symptoms of a brain tumour in patients, including debilitating daily headaches and compression of the optic nerve.
The usual age of onset for IIH is between 20 and 30 years, and the condition is statistically most common in women who are obese.
IIH is considered to be a rapidly-growing orphan indication.
Its incidence has increased by more than 350% in the last 10 years.