Nucala (mepolizumab) is the first anti-IL5 biologic to report positive phase 3 results in patients with nasal polyps
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Issued: London, UK
Pivotal data support regulatory filing for additional eosinophil-driven disease
GlaxoSmithKline plc (GSK) today announced positive results from the pivotal SYNAPSE study of Nucala (mepolizumab) in patients suffering from chronic rhinosinusitis with nasal polyps (CRSwNP). This is the first time an anti-IL5 biologic has reported positive phase 3 data in CRSwNP, and adds to the range of eosinophil-driven diseases in which Nucala has efficacious data.
SYNAPSE is the first study to evaluate the benefit of biologic treatment for patients all of whom had a history of previous surgery (approximately one in three had ≥3 surgeries) and were in need of further surgery due to severe symptoms and increased size of their polyps.
Dr. Hal Barron, Chief Scientific Officer and President R&D, GSK, said: “Nasal polyps are a common condition impacting many activities that most people take for granted, such as sleeping, breathing and having a sense of smell and taste. These results show that Nucala can reduce symptoms and need for surgery in patients with nasal polyps, and we look forward to progressing this regulatory submission.”
The study met both co-primary endpoints, with mepolizumab, added to standard of care, demonstrating statistically significant improvements in both the size of nasal polyps (p<0.001) at week 52 and in nasal obstruction (p<0.001) during weeks 49-52, compared to placebo added to standard of care:
- Difference in median change from baseline for total endoscopic nasal polyps score: -0.73 (95% CI: -1.11, -0.34)
- Difference in median change from baseline for nasal obstruction visual analogue scale score: -3.14 (95% CI: -4.09, -2.18)
The key secondary endpoint of time to first actual nasal surgery up to week 52 was also statistically significant, with mepolizumab, added to standard of care, showing a reduction of 57% (p=0.003) versus placebo added to standard of care (hazard ratio [95% CI]: 0.43 [0.25, 0.76]).
Claus Bachert, MD, Professor and Chief of Clinics ENT Department at Ghent University said: “The impact of CRSwNP on patients is substantial, but often underestimated. Treatment options are currently limited. These results show mepolizumab represents a promising alternative for patients who are caught in a cycle of surgeries. Each surgery carries risks and can disable the patient for several weeks.”
The safety results in the study were consistent with the known profile of mepolizumab.
Based on these data, GSK plans to progress regulatory submissions in 2020. Mepolizumab is currently not approved for treatment of CRSwNP anywhere in the world.
About chronic rhinosinusitis with nasal polyps (CRSwNP)
CRSwNP is a chronic inflammatory disease of the nasal passage linings or sinuses leading to soft tissue growth known as nasal polyps in the upper nasal cavity and is characterised by elevated levels of eosinophils. The resultant swellings can grow in both nostrils (bilateral) resulting in chronic rhinosinusitis, greatly impacting a patient’s quality of life due to nasal obstruction, loss of smell, facial pain, facial pressure and nasal discharge. High levels of IL-5 have been detected in patients with CRSwNP and eosinophilic inflammation is associated with recurrence of polyps post-surgery. The current standard of care is treatment with intranasal corticosteroids and, for severe cases, intermittent courses of oral corticosteroids. A monoclonal antibody inhibiting the signalling of IL4 and IL13 has recently been approved for use. Surgery to remove the polyp tissue may also be indicated for severe cases. However, polyps have a strong tendency to reoccur often leading to repeat surgery.
About the phase 3 study
The pivotal phase 3 study named SYNAPSE, StudY in NAsal Polyps patients to assess the Safety and Efficacy of mepolizumab, was a 52-week, randomised, double-blind, parallel group study. It assessed the efficacy and safety of the liquid formulation of mepolizumab 100mg added to standard of care compared to placebo added to standard of care, administered subcutaneously using a pre-filled syringe every 4 weeks for 52 weeks, in just over 400 adult patients with recurrent severe bilateral nasal polyps. Patients with severe bilateral nasal polyps were defined as those with an average nasal obstruction VAS symptom score > 5 and an endoscopic score of at least 5 out of a maximum score of 8, with a minimum score of 2 in each nasal cavity. Patients must also have had a history of at least one prior surgery for nasal polyps in the previous 10 years, have recurrent nasal polyps despite treatment with standard of care and in current need of nasal polyp surgery.
First approved in 2015 for severe eosinophilic asthma (SEA), 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 to normal levels. At normal levels eosinophils may play a role in maintaining health.
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 SEA. It is approved for paediatric use from ages six to 17 in Europe and the US and several other markets in SEA. 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). Regulatory submissions for Hypereosinophilic Syndrome are expected to progress in 2020. In addition to CRSwNP, mepolizumab is currently being investigated for 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.
Important safety information
The following information is based on the US Prescribing Information for Nucala in licensed indications only. Please consult the full Prescribing Information for all the labelled safety information for Nucala.
Nucala should not be administered to patients with a history of hypersensitivity to mepolizumab or excipients in the formulation.
WARNINGS AND PRECAUTIONS
- Hypersensitivity reactions (e.g., anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, rash) have occurred after administration of Nucala. Discontinue Nucala in the event of a hypersensitivity reaction.
- Do not use to treat acute bronchospasm or status asthmaticus.
- Herpes zoster infections have occurred in patients receiving Nucala. Consider vaccination if medically appropriate.
- Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with Nucala. Decrease corticosteroids gradually, if appropriate.
- Treat patients with pre-existing helminth infections before therapy with Nucala. If patients become infected while receiving treatment with Nucala and do not respond to anti-helminth treatment, discontinue Nucala until parasitic infection resolves.
Most common adverse reactions (incidence ≥5%) in severe asthma clinical trials included headache, injection site reaction, back pain, and fatigue. Injection site reactions (eg, pain, erythema, swelling, itching, burning sensation) occurred in 8% of subjects treated with 100 mg of Nucala versus 3% treated with placebo.
In a clinical trial in patients with EGPA receiving 300 mg of Nucala, no additional adverse reactions were identified to those reported in severe asthma clinical trials. Injection site reactions (eg, pain, erythema, swelling) occurred in 15% of subjects treated with 300 mg of Nucala versus 13% treated with placebo.
GSK’s commitment to respiratory disease
For over 50 years, GSK has led the way in developing medicines that advance the management of asthma and COPD. From introducing the world’s first selective short-acting beta agonist in 1969, to launching six treatments in five years to create today’s industry-leading respiratory portfolio, we continue to innovate so we can reach the right patients, with the right treatment. Working together with the healthcare community, we apply world-class science to discover and understand the molecules that become the medicines of tomorrow. We won’t stand still until the simple act of breathing is made easier for everyone.
GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com/about-us.
Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D 'Principal risks and uncertainties' in the company's Annual Report on Form 20-F for 2019.
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