GlaxoSmithKline’s Lung Drug Passes Phase III Test

Issued: London.

• Data supports regulatory submission by GSK in Europe by end of 2016

• GSK’s US filing plans remain on track with submission also expected by end of 2016

GlaxoSmithKline plc (LSE/NYSE: GSK) and Innoviva, Inc. (NASDAQ: INVA) today announced positive top-line results from the pivotal phase III FULFIL study of the investigational once-daily ‘closed’ triple combination therapy, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI: a combination inhaled corticosteroid, long-acting muscarinic antagonist, long-acting beta agonist), in patients with chronic obstructive pulmonary disease (COPD).

The study met its two co-primary endpoints, demonstrating statistically significant improvements compared with twice-daily Symbicort^® Turbohaler^® (budesonide/formoterol 400/12mcg) in both lung function as measured by trough FEV₁ (171mL, 95% confidence interval [148, 194] p<0.001), and health-related quality of life as measured by the St. George’s Respiratory Questionnaire (SGRQ) (-2.2 units, 95% confidence interval [-3.5, -1.0] p<0.001), at the end of the 24-week study period. The proportion of patients who responded with the minimum clinically important difference in SGRQ (-4 units) was 50% on FF/UMEC/VI and 41% on budesonide/formoterol.

The safety profile of the closed triple combination at both 24 weeks and the 52-week extension was consistent with the known profile of the individual medicines and their combinations. At 24 and 52 weeks, the most common adverse events across both treatment arms were nasopharyngitis, headache and COPD worsening.

At 24 weeks, the incidence of investigator-reported serious adverse events was 5.4% and 5.7% for FF/UMEC/VI and budesonide/formoterol, respectively, of which the incidence of worsening of COPD was 1.3% and 2.3%; for pneumonia was 1.0% and 0.3%; and for cardiac disorders was 0.3% and 1.0%, respectively.

At 52 weeks, the incidence of investigator-reported serious adverse events was 10.0% for FF/UMEC/VI and 12.7% for budesonide/formoterol, respectively, of which the incidence of worsening of COPD was 2.4% and 9.1%; for pneumonia was 1.9% and 1.8%; and for cardiac disorders was 1.4% and 0.9%, respectively.

Dave Allen, Head of Respiratory R&D at GSK, said: “We are delighted with the outcome of the FULFIL study, which marks a further step towards making this closed triple combination therapy available to appropriate patients with COPD. Triple combination therapy is already a reality for many patients with COPD and is dispensed in multiple inhalers. By combining three medicines in a single inhaler we can offer a convenient, once-daily dosing option to patients while improving their symptoms.”

Mike Aguiar, CEO of Innoviva, Inc, commented: “With the FULFIL study, we have shown meaningful improvements in lung function and health-related quality of life when combining three COPD medicines in a single inhaler, compared to the dual therapy of budesonide/formoterol. If approved, a once-daily triple combination would be an important addition to our portfolio of combination respiratory products partnered with GSK including Relvar^®/Breo^® Ellipta^® and Anoro^® Ellipta.”

Findings from the FULFIL study support GSK’s plans for an EU regulatory submission of the closed triple combination therapy for COPD which is expected by the end of 2016.

As announced on 2 June 2016, GSK also intends to submit a New Drug Application for the closed triple combination therapy in COPD to the US Food and Drug Administration (FDA) by the end of 2016.

The closed triple therapy is a combination of three medicines: fluticasone furoate (FF), an inhaled corticosteroid (ICS), umeclidinium (UMEC), a long-acting muscarinic antagonist (LAMA) and vilanterol (VI), a long-acting beta₂-adrenergic agonist (LABA) delivered once-daily in GSK’s Ellipta^® inhaler. The FULFIL study compared FF/UMEC/VI with budesonide and formoterol, an ICS/LABA combination delivered twice-daily in the Turbohaler dry powder inhaler.

Full results from the FULFIL study, including data from secondary endpoints and the 52-week extension study, will be submitted for presentation at a scientific congress.

FULFIL (Lung FUnction and quality of LiFe assessment in COPD with closed trIpLe therapy) was a randomised, double-blind, double-dummy, parallel group multicentre study evaluating once-daily FF/UMEC/VI (100mcg/62.5mcg/ 25mcg) inhalation powder versus twice-daily budesonide/formoterol (400mcg/12mcg) via the Turbohaler dry powder inhaler. In the study, 1,810 patients were treated across 162 study centres globally (911 on FF/UMEC/VI and 899 on budesonide/formoterol).

The co-primary endpoints were: change from baseline in trough FEV1 and SGRQ total score after 24 weeks of treatment. Other endpoints included the effect of FF/UMEC/VI on the annual rate of moderate/severe exacerbations compared with budesonide/formoterol, and the safety profile of FF/UMEC/VI compared with budesonide/formoterol over 24 weeks and 52 weeks of treatment. To provide additional longer term safety data, a sub-set of 430 patients remained on blinded study treatment for up to a total of 52 weeks. Adverse events of particular interest included pneumonia and cardiovascular risk. Patient perspectives of efficacy and physical activity will also be evaluated for FF/UMEC/VI versus budesonide/formoterol.

In addition to FULFIL, the IMPACT (InforMing the PAthway of COPD Treatment) study, which began in 2014 and is expected to complete in 2017, is investigating whether FF/UMEC/VI can reduce the rate of exacerbations compared with two, once-daily dual therapies from GSK’s existing portfolio: Relvar/Breo (FF/VI), an ICS/LABA combination and Anoro (UMEC/VI), a LAMA/LABA combination.

The closed triple combination of FF/UMEC/VI is not approved for use anywhere in the world.

COPD is a disease of the lungs that includes chronic bronchitis, emphysema or both. COPD is characterised by obstruction to airflow that interferes with normal breathing.COPD is thought to affect 329 million people worldwide.

Long-term exposure to lung irritants that damage the lungs and the airways are usually the cause of COPD. Cigarette smoke, breathing in second hand smoke, air pollution, chemical fumes or dust from the environment or workplace can all contribute to COPD. Most people who have COPD are at least 40 years old when symptoms begin.

Innoviva – Innoviva is focused on bringing compelling new medicines to patients in areas of unmet need by leveraging its significant expertise in the development, commercialization and financial management of bio-pharmaceuticals. Innoviva’s portfolio is anchored by the respiratory assets partnered with Glaxo Group Limited (GSK), including RELVAR®/BREO® ELLIPTA® and ANORO® ELLIPTA®, which were jointly developed by Innoviva and GSK. Under the agreement with GSK, Innoviva is eligible to receive associated royalty revenues from RELVAR®/BREO® ELLIPTA®, ANORO® ELLIPTA® and, if approved and commercialized, VI monotherapy, as well. In addition, Innoviva retains a 15 percent economic interest in future payments made by GSK for earlier-stage programs partnered with Theravance Biopharma, Inc., including the closed triple combination therapy for COPD. For more information, please visit Innoviva’s website at www.inva.com.

GSK – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com.

RELVAR^®, BREO^®, ANORO^® and ELLIPTA^® are trademarks of the GlaxoSmithKline group of companies. SYMBICORT® and TURBOHALER® are trademarks of AstraZeneca.

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