GSK美泊利单抗临床3期达到主要终点

红茶.

GlaxoSmithKline plc (GSK) today announced positive results from the pivotal study of Nucala (mepolizumab) in the treatment of patients living with Hypereosinophilic Syndrome (HES), making it the first treatment to demonstrate a reduction in flares for this rare disease.


The phase 3 study met its primary endpoint, demonstrating a statistically significant result with 50% fewer patients experiencing a HES flare (worsening of symptoms or eosinophil threshold requiring an escalation in therapy) when treated with mepolizumab, compared to placebo, when added to standard of care treatment over the 32-week study period (56% vs 28%; p=0.002).


Dr Hal Barron, Chief Scientific Officer and President, R&D, GSK, said: “Mepolizumab has the potential to change the treatment landscape for patients with HES which is a complex and debilitating disease with limited therapeutic options today.”


Secondary endpoints from the study were also statistically significant and supported the primary endpoint, showing:


Risk of first HES flare over the study period was 66% lower for patients treated with mepolizumab compared to placebo (hazard ratio 0.34; 95% CI 0.18, 0.67).
There was a 66% reduction in the annualised rate of HES flares versus placebo (rate ratio 0.34; 95% CI 0.19, 0.63).
Fatigue scores improved in mepolizumab compared to placebo (p=0.036).
The safety results in the study were consistent with the known profile of mepolizumab.
Dr Gerald Gleich, MD, allergist, immunologist and HES expert, University of Utah, said: “Mepolizumab is thought to work by reducing blood eosinophil levels and evidence suggests it has potential as a targeted treatment option for a range of inflammatory diseases driven by raised eosinophils. These data are very promising and should provide hope for patients affected by this rare, life-threatening condition caused by eosinophilic inflammation”.


Based on these data, GSK plans to progress regulatory submissions in 2020. Mepolizumab is not approved for use in HES anywhere in the world. Further results from the study will be submitted for future presentation at upcoming scientific meetings and in peer-reviewed publications.


About Hypereosinophilic Syndrome (HES)


HES is a rare group of inflammatory disorders that affects approximately 20,000 people globally. Patients with the condition have a persistent and marked overproduction of eosinophils, a type of white blood cell. When eosinophils infiltrate certain tissues, they can cause inflammation and organ damage which, over time, can impact patients’ day-to-day ability to function. Complications can range from fever and malaise to respiratory and cardiac problems. If left untreated, the symptoms of HES become progressively worse and the disease can be life-threatening.


About the phase 3 study


The pivotal phase 3 study, which enrolled 108 patients, is a 32-week, randomised, double-blind, placebo-controlled study to investigate the efficacy and safety of subcutaneous mepolizumab 300mg (3x100) every four weeks compared with placebo in adolescent and adult patients with severe HES. Severe HES was defined by at least two HES flares within the past 12 months and a blood eosinophil count of 1000 cells/μL or higher. Mepolizumab for HES has received both Fast Track and Orphan Drug designations by the US Food and Drug Administration (FDA). The European Medicines Agency (EMA) has granted Orphan Drug Designation to mepolizumab for the treatment of HES.


About mepolizumab


First approved in 2015 for severe eosinophilic asthma, mepolizumab is the first-in-class monoclonal antibody that targets IL-5. It is believed to work by preventing IL-5 from binding to its receptor on the surface of eosinophils reducing blood eosinophils without completely depleting them.


Mepolizumab has been developed for the treatment of diseases that are driven by inflammation caused by eosinophils. It has been studied in over 3,000 patients in 21 clinical trials across a number of eosinophilic indications and has been approved (under the brand name Nucala) in the US, Europe and in over 20 other markets, as an add-on maintenance treatment for patients with severe eosinophilic asthma (SEA). It is approved for paediatric use from ages six to 17 in Europe and the US in severe eosinophilic asthma. In the US, Japan and Canada and a number of other markets, it is approved as add-on maintenance treatment for patients with eosinophilic granulomatosis with polyangiitis (EGPA). In addition to HES, it is currently being investigated for nasal polyposis and COPD.


Mepolizumab is not approved for the relief of acute bronchospasm or status asthmaticus. Full US Prescribing Information is available at US Prescribing Information Nucala.