Experimental drugs for the treatment of idiopathic intracranial hypertension (IIH): shedding light on phase I and II trials

ABSTRACT

Introduction

Idiopathic intracranial hypertension is a neurological condition characterized by a raised intracranial pressure and papilledema that causes debilitating headaches. While the extent of the pathophysiology is being discovered, the condition is emerging as a systemic metabolic disease distinct to people living with obesity alone. Idiopathic intracranial hypertension is becoming more common and therefore establishing licensed therapeutics is a key priority.

Area covered

The translation of preclinical work in idiopathic intracranial hypertension is evident by the two early phase trials evaluating 11-β-hydroxysteroid dehydrogenase inhibitor, AZD4017, and a glucagon like peptide-1 receptor agonist, Exenatide. This review summarizes these two early phase trials evaluating targeted medicines for the treatment of intracranial pressure. The modulation of these two distinct mechanisms have potential for therapeutic intervention in people living with idiopathic intracranial hypertension.

Expert opinion

The clinical trial landscape in idiopathic intracranial hypertension is a challenge due to the rarity of the disease and the lack of agreed meaningful trial outcomes. Further preclinical work to fully understand the pathogenesis is required to enable personalized targeted drug treatment.

KEYWORDS:

• Cerebrospinal fluid
• intracranial pressure
• headache
• 11-β-hydroxysteroid dehydrogenase
• glucagon-like peptide 1
• outcome measures
• obesity
• papilledema

Article highlights

• Licenced treatments for Idiopathic Intracranial Hypertension are an unmet clinical need recognized by patients and healthcare professionals.

• There are currently only two early phase trials evaluating novel medical therapies in people with active for Idiopathic Intracranial Hypertension.

• Use of 11β-HSD1 inhibitor, AZD4017, was found to be safe in people with Idiopathic Intracranial Hypertension. This phase two study was not powered to detect a difference in intracranial pressure outcomes. AZD4017 administration had significant beneficial systemic actions of reducing total cholesterol, increasing high density lipoprotein (HDL) cholesterol and improved lean muscle mass.

• Use of the glucagon like peptide-1 receptor agonist, Exenatide, was found to be safe in people with Idiopathic Intracranial Hypertension. Significant reduction in intracranial pressure, as measured using intracranial pressure monitors, was observed following administration at 2.5 h, 24 h, and 12 weeks.

Declarations of interest

S Mollan has received payment for consultancy work from Invex Therapeutics. She has received payment for advisory boards from Gentech and Ocular Therapeutix. Grant funding has been paid to her institution from the National Institute of Health Research (NIHR131211), UK Space Agency, and IIHUK. They have also received Honoria from Novartis for speaking on fundoscopy, but within a National headache network meeting (2019); Chiesi (2020,2021), Heidelberg Engineering (2019, 2020,2021), and Teva (2019, 2021).

A Sinclair has received speaker fees and Honoraria from Novartis (erenumab) and Allergan (BOTOX), in addition, Invex therapeutics, company director with salary and stock options (2019, 2020, 2021, 2022, 2023). Grant funding has been paid to her institution from the National Institute of Health Research (NIHR131211), a Sir Jules Thorn Award for Biomedical Science, UK Space Agency and the UK Ministry of Defence.

L Hill has received grant funding that has been paid to her institution from Fight for Sight, Medical Research Council, Kennedy Trust for Rheumatology Research, Alzheimer’s research, UK.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13543784.2023.2288073

Additional information

Funding

This paper was not funded.