Depemokimab (brand name Exdensur) has been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) and is the first and only ultra-long-acting biologic with twice-yearly dosing to treat severe asthma and rhinosinusitis.
This monoclonal antibody is now indicated as an add-on maintenance treatment for asthma in adults and adolescents aged 12 years and older with type 2 inflammation characterised by an eosinophilic phenotype who are inadequately controlled on maximum moderate- or high-dose inhaled corticosteroids (ICS) plus another asthma controller.
Depemokimab is also indicated as an add-on therapy with intranasal corticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps (CRSwNP) for whom therapy with systemic corticosteroids and/or surgery do not provide adequate control.
Delivered by subcutaneous injection every six months, depemokimab works by blocking interleukin-5 – a key cytokine in type 2 inflammation.
Julian Beach, interim executive director of healthcare quality and access at the MHRA, said: ‘These conditions affect a significant number of people across the UK, and in some cases can be difficult to manage despite existing treatments.
‘This approval represents another potential treatment option for patients living with some forms of these conditions whose symptoms have not been adequately controlled with current therapies.’
Kaivan Khavandi, SVP and global head, respiratory, immunology and inflammation R&D at GSK said the approval has the potential to redefine care for millions of patients.
He added: ‘This ultra-long-acting biologic delivers sustained efficacy to reduce asthma exacerbations, keep patients out of hospital and help prevent cumulative lung damage in just two doses a year.’
Safety and efficacy of depemokimab
The MHRA approval was based on the findings from the SWIFT and ANCHOR phase 3 trials, which showed sustained efficacy with a twice-yearly dosing regimen for depemokimab.
The pooled results from the SWIFT trials looking at severe eosinophilic asthma showed a 54% reduction in clinically significant exacerbations over 52 weeks [rate ratio 0.46, 95% confidence interval (0.36, 0.59), nominal p<0.001] (AER depemokimab = 0.51 exacerbations per year versus placebo = 1.11).
It also showed a 72% reduction [RR 0.28, 95% CI (0.13, 0.61), nominal p=0.002] (AER: depemokimab = 0.02 vs placebo = 0.09) in the secondary endpoint of clinically significant exacerbations requiring hospitalisation or emergency department visit compared to placebo.
The open-label 12-month extension AGILE study, found depemokimab maintained these results and confirmed the sustained safety and efficacy of a twice-yearly dose of depemokimab over the course of two years.
Pooled results from the ANCHOR trials for CRSwNP showed an improvement from baseline in nasal polyp score (scale: 0-8) at 52 weeks [treatment difference -0.7, 95% CI (-0.9, -0.4), nominal p<0.001] and in nasal obstruction verbal response scale (scale: 0-3) over weeks 49-52 [treatment difference -0.24, 95% CI (-0.39, -0.08), nominal p=0.003].
Across all the trials, depemokimab was well-tolerated, with a frequency and severity of adverse events similar to that in the placebo group. No serious adverse events or deaths were considered by the investigator to be related to depemokimab. However, the most common side effects noted by the MHRA included itchy skin, headache, tiredness and injection-site reactions.
A review of depemokimab for use on the NHS is currently underway by the National Institute for Health and Care Excellence (NICE) to treat severe eosinophilic asthma in people 12 years and over. A similar NICE review for chronic rhinosinusitis with nasal polyps has, at the time of writing, been suspended.
Depemokimab has also recently received a positive CHMP opinion in the EU.
This article was originally published by our sister publication Hospital Healthcare Europe.
