Issued: London UK – LSE Announcement
GlaxoSmithKline plc (LSE/NYSE: GSK) today announced the outcome of the Pulmonary Allergy Drugs Advisory Committee of the United States (US) Food and Drug Administration (FDA) meeting on the use of mepolizumab as an add-on treatment to inhaled corticosteroid-based maintenance treatment for the reduction of exacerbations in patients with chronic obstructive pulmonary disease (COPD) guided by blood eosinophil counts. The committee voted on the basis of data presented that the risk-benefit profile was not adequate to support approval (3 for, 16 against).
The committee also voted that there was not substantial evidence of the efficacy (3 for, 16 against) but there was adequate evidence of the safety (17 for, 2 against) of mepolizumab in this population and the committee suggested further data to characterise the patient population that would be most likely to benefit from this targeted biologic therapy.
Dave Allen, SVP Respiratory Therapy Area, R&D, GSK, said: “Having participated in today’s advisory committee meeting and heard the recommendation we will continue to work with the FDA to address outstanding questions. We remain confident our data supports mepolizumab as a targeted treatment for patients continuing to experience COPD exacerbations guided by blood eosinophil count.”
FDA Advisory Committees provide non-binding recommendations for consideration by the FDA. The Prescription Drug User Fee Act (PDUFA) goal date for mepolizumab is 7 September 2018.
Mepolizumab is not currently approved for use in COPD anywhere in the world and if approved it would be the first biologic therapy for patients with COPD.
Mepolizumab has been developed for the treatment of diseases that are driven by inflammation linked to higher-than-normal eosinophils. Mepolizumab 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 and is the leading biologic in this indication. In the US, Canada and Japan it is approved as add-on maintenance treatment for patients with eosinophilic granulomatosis with polyangiitis (EGPA).
This supplementary Biologics License Application (sBLA) was submitted to the FDA in November 2017 for approval as an add-on treatment to inhaled corticosteroid-based maintenance treatment for the reduction of exacerbations in patients with chronic obstructive pulmonary disease (COPD) guided by blood eosinophil counts.
Chronic obstructive pulmonary disease (COPD) is a common disease characterised by progressive airflow obstruction, chronic inflammation in the lungs, breathlessness and acute exacerbations. An important goal of COPD therapy is to prevent the risk of exacerbations which are characterised by periods of acute worsening of symptoms, deterioration in lung function, decreased health-related quality of life and a potentially permanent decline in lung function. About 30-40% of moderate to severe COPD patients on standard of care triple inhaled therapy remain uncontrolled and continue to experience exacerbations
COPD affects an estimated 384 million people worldwide, including nearly 16 million diagnosed in the U.S., and is predicted to be the third leading cause of death worldwide by 2020.
About COPD and eosinophil inflammation
Eosinophils (a type of white blood cell) when present in the body in normal levels can play a role in protecting the body against infection. However, the overproduction of eosinophils can cause inflammation in vital organs and tissues, sometimes permanently damaging them and is believed to contribute to the development of inflammatory diseases including severe asthma and COPD. Eosinophil counts may be associated with a risk of COPD exacerbations. The fact that some of these patients continue to have exacerbations despite inhaled triple therapy provides a strong rationale for therapies that specifically inhibit eosinophilic inflammation.
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. Inhibiting IL-5 binding in this way reduces blood eosinophils.
Mepolizumab has been studies in over 3000 patients in 16 clinical trials across a number of eosinophilic indications and is currently being investigated for severe hypereosinophilic syndrome and nasal polyposis, in addition to the sBLA filed for the treatment of patients with COPD.
GSK’s commitment to respiratory disease
GSK has led the way in developing innovative medicines to advance the management of asthma and COPD for nearly 50 years. Over the last five years we have launched six innovative medicines responding to continued unmet patient need, despite existing therapies. This is an industry-leading portfolio in breadth, depth and innovation, developed to reach the right patients, with the right treatment.
Important safety information for Nucala (mepolizumab)
The following information is based on the US Prescribing Information for Nucala in patients with severe eosinophilic asthma and EGPA. 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 following administration of Nucala. These reactions generally occur within hours of administration but in some instances can have a delayed onset (i.e. days). In the event of a hypersensitivity reaction, Nucala should be discontinued.
Acute Asthma Symptoms or Deteriorating Disease
Nucala should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm.
Opportunistic Infections: Herpes Zoster
Herpes zoster infections have occurred in patients receiving Nucala. Consider vaccination if medically appropriate.
Reduction of Corticosteroid Dosage
Do not discontinue systemic or inhaled corticosteroids (ICS) abruptly upon initiation of therapy with Nucala. Decreases in corticosteroid doses, if appropriate, should be gradual and under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.
Parasitic (Helminth) Infection
Treat patients with pre-existing helminth infections before initiating therapy with Nucala. If patients become infected while receiving Nucala and do not respond to anti-helminth treatment, discontinue Nucala until infection resolves.
ADVERSE REACTIONS: SEVERE ASTHMA
The most common adverse reactions (≥3% and more common than placebo) reported in the first 24 weeks of two clinical trials with Nucala (and placebo) were: headache, 19% (18%); injection site reaction, 8% (3%); back pain, 5% (4%); fatigue, 5% (4%); influenza, 3% (2%); urinary tract infection 3% (2%); abdominal pain upper, 3% (2%); pruritus, 3% (2%); eczema, 3% (<1%); and muscle spasm, 3% (<1%).
Systemic Reactions, including Hypersensitivity Reactions: In 3 clinical trials, 3% of subjects who received Nucala experienced systemic (allergic and nonallergic) reactions compared to 5% in the placebo group. Manifestations included rash, flushing, pruritus, headache, and myalgia.. A majority of the systemic reactions were experienced on the day of dosing. Reports of anaphylaxis have been received postmarketing.
Injection site reactions (e.g. pain, erythema, swelling, itching, burning sensation) occurred at a rate of 8% in subjects treated with Nucala compared with 3% in subjects treated with placebo.
ADVERSE REACTIONS: EGPA
In a 52-week 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.
Systemic Reactions, including Hypersensitivity Reactions: Systemic (allergic and nonallergic) reactions occurred in 6% of subjects receiving 300 mg of NUCALA and 1% placebo. Manifestations of systemic allergic reactions included rash, pruritus, flushing, fatigue, hypertension, warm sensation in trunk and neck, cold extremities, dyspnea, and stridor. The reported manifestation of systemic non-allergic reactions was angioedema. Two of the four (50%) systemic reactions in subjects receiving 300 mg of NUCALA were experienced on the day of dosing.
Injection site reactions (eg, pain, erythema, swelling) occurred in 15% of subjects treated with 300 mg of NUCALA versus 13% treated with placebo.
USE IN SPECIFIC POPULATIONS
The data on pregnancy exposures from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies, such as mepolizumab, are progressively transported across the placenta in a linear fashion as pregnancy progresses; therefore, potential effects on a foetus are likely to be greater during the second and third trimesters of pregnancy.
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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 2017.