Tuesday, 22 September 2015
Positive Phase III results to be presented for LAMA/LABA PT003 in COPD
AstraZeneca will present 33 abstracts from across the respiratory disease portfolio at the 2015 European Respiratory Society (ERS) meeting in Amsterdam, Netherlands, 26-30 September. Data will include results from AstraZeneca’s growing inhaled portfolio of LAMA/LABA therapies, as well as findings from the company’s biologics pipeline and early science programmes.
Maarten Kraan, Vice President, Respiratory, Inflammation and Autoimmune Therapy Area, said: “The data presented at ERS further demonstrate the diversity of AstraZeneca’s portfolio of innovative formulations and devices which provide physicians with the opportunity to select the right therapy to meet their patients’ needs today and in the future.”
Data from growing inhaled respiratory portfolio reinforce importance of delivering combination therapies in a single device
Among key abstracts being presented at ERS are the positive Phase III safety and efficacy data for PT003, the investigational therapy combining glycopyrronium and formoterol fumarate in a pressurised metered dose inhaler (pMDI).
The two pivotal 24 week studies, PINNACLE-1 and PINNACLE-2, investigated the potential of PT003 to improve lung function in patients with Chronic Obstructive Pulmonary Disease (COPD) and showed that the investigational therapy had positive effects on both co-primary and secondary endpoints.1 There were no unexpected safety findings, with adverse events being consistent with previous results from the development programme [#PA4363, Tuesday 29 September, 12:50-14:40 CET]1.
Colin Reisner, Head of Clinical, Respiratory Global Medicines at AstraZeneca, said: “These positive data demonstrate the important role of dual bronchodilators as a treatment for managing COPD. They further support our global regulatory submissions for the first LAMA/LABA combination to be delivered in a pMDI using our unique co-suspension technology.”
Other key data to be presented from the company’s inhaled COPD portfolio includes a study assessing the efficacy and safety of Duaklir Genuair (aclidinium bromide/formoterol fumarate), AstraZeneca’s fixed-dose combination LAMA/LABA therapy. The study assessed morning and night-time symptom prevalence in COPD and the efficacy of aclidinium bromide/formoterol fumarate in symptomatic versus asymptomatic patients [#OA1968, Monday 28 September, 10:45-12:45 CET]2.
Data highlights from the company’s biologics portfolio show progress in the application of targeted approaches for future respiratory care
Study evaluating the effect of tralokinumab on serum periostin and Immunoglobin E (IgE) levels in uncontrolled severe asthma [#OA1770, Monday 28 September, 08:30-10:30 CET].
- Serum periostin has been proposed as a surrogate biomarker for activation of the IL-13 pathway in the lung. The reduction of serum periostin by tralokinumab in subjects with severe uncontrolled asthma further supports this concept.
- IgE contributes to the signs and symptoms of asthma and IL-13 induces B cells to produce IgE. The reduction of IgE levels by tralokinumab may help explain its mechanism of action in reducing exacerbations and improving asthma control and asthma-related quality of life that were observed in a subgroup of patients in the Phase IIb trial.
- Both findings will be explored further in the ongoing STRATOS Phase III trials.
Highlights from AstraZeneca’s early respiratory portfolio to be presented include:
Data on the company’s inhaled p38 inhibitor (AZD7624), aimed at delivering a broad anti-inflammatory effect in COPD patients [#PA3904, Tuesday 29 September, 12:50-14:40 CET; #PA3950, Tuesday 29 September, 12:50-14:40 CET, and #OA483, Sunday 27 September, 10:45-12:45 CET] 3,4,5.
The complete list of AstraZeneca data presentations can be accessed on the ERS website here.
NOTES FOR EDITORS
About PT003 (glycopyrronium/formoterol fumarate)
PT003 is under investigation as a twice-daily fixed-dose combination of glycopyrronium, a long-acting muscarinic antagonist (LAMA) and formoterol fumarate, a long-acting beta-2 agonist (LABA). PT003 would be the first LAMA/LABA combination to be delivered in a pressurised metered dose inhaler (pMDI) using the unique porous particle Co-Suspension Technology 1.
About the PINNACLE Phase III Pivotal Studies
The PT003 Phase III pivotal programme consists of PINNACLE-1, PINNACLE-2, and an extension study, PINNACLE-3. Overall the Phase III pivotal programme enrolled over 3,700 patients with COPD at over 275 study sites 6,7,8.
PINNACLE-1 and PINNACLE-2 were Phase III randomised, double-blind, multi-centre, placebo-controlled studies. In both studies, the efficacy and safety of PT003 administered twice daily via pressurised metered dose inhaler (pMDI) was compared to its monotherapy components: glycopyrronium (PT001), a LAMA, and formoterol fumarate (PT005), a LABA, and placebo. PT001 and PT005 were also compared to placebo 6,7. In PINNACLE-1, open-label tiotropium was included as an active control. Both studies were conducted over 24 weeks in subjects with moderate to very severe COPD 6,7.
The primary objective of both studies was improvement in lung function as assessed by change from baseline in trough FEV 1 6,7.
PINNACLE-3 was a multi-centre, randomised, double-blind, parallel-group, chronic dosing, active-controlled, 28-week safety extension study of the two pivotal 24-week studies (PINNACLE-1 and PINNACLE-2). It was designed to evaluate the long-term safety, tolerability, and efficacy of PT003 administered twice daily via pMDI compared to PT001 and PT005 in patients with moderate to very severe COPD over a total observation period of 52 weeks. Open-label tiotropium served as the active control8.
The successful completion of the PINNACLE studies marks the first Phase III outcomes from a series of pipeline candidates under development by AstraZeneca using Pearl’s novel technology. The top-line results from the PINNACLE-1 and PINNACLE-2 studies were announced on 18 March, 2015.
About Duaklir Genuair (aclidinium bromide/formoterol fumarate)
Aclidinium bromide/formoterol fumarate 340/12 µg is an approved fixed-dose LAMA/LABA combination of two long-acting bronchodilators – aclidinium bromide is a long acting muscarinic antagonist (LAMA) and formoterol fumarate is a long-acting beta-agonist (LABA).
Both aclidinium bromide and formoterol fumarate are separately approved for the maintenance treatment of COPD in Europe and the United States. The fixed-dose combination was approved by the European Medicines Agency for COPD in November 2014. Duaklir Genuair is also approved in Canada and South Korea.
Tralokinumab is a human IgG4 monoclonal antibody that targets IL-13, a key cytokine that is believed to play a key role in the pathogenesis of asthma through the promotion of inflammation, airway hyper-responsiveness, mucus hyper-secretion, airway remodelling via fibrosis, increased IgE synthesis and mast cell activation. Tralokinumab is currently in Phase III trials for severe asthma and in Phase II trials for atopic dermatitis.
Asthma is a chronic inflammatory disorder of the airways in which the bronchi are reversibly narrowed. It affects people of all ages and is a significant source of morbidity and mortality worldwide causing an estimated 250,000 deaths per year. Asthma can be allergic (induced by an immune response to inhaled allergens such as pollen, fungal spores or dust mite particles) or non-allergic (induced by exercise, cough, viral respiratory infection, or inhalation of smoke or chemicals in the workplace). The airway narrowing characteristic of asthma is a response of the immune system to the asthma trigger.
Severe persistent asthma is classified by the frequency of symptoms throughout the day and night, use of reliever inhalers, interference with daily activities, peak flow readings and whether asthma exacerbations require use of oral systemic corticosteroids more than twice a year. Asthma treatment usually includes inhaled corticosteroids that reduce inflammation of the airways to prevent asthma symptoms and exacerbations, combined with long-acting β2-agonist bronchodilators and a short-acting β2-agonist or other bronchodilator for relief.
COPD (chronic obstructive pulmonary disease) is a progressive disease associated mainly with tobacco smoking, air pollution or occupational exposure, which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness. It affects an estimated 300 million people worldwide and is predicted to be the third leading cause of death by 203020. Improving lung function and managing daily symptoms such as breathlessness are important to the management of COPD. It is estimated that eight out of 10 patients suffer symptoms at night, such as an irritative cough and difficulty breathing, frequent nocturnal awakenings, which leads to insomnia, worry and anxiety.
About AstraZeneca in Respiratory Disease
AstraZeneca has a long heritage in respiratory disease with 40 years of experience and a strong franchise of marketed products. Our efforts to find ground-breaking medicines and to develop new technologies are underpinned by a deep understanding of the biology of respiratory diseases and our extensive experience in primary care medicine.
Our strategy is to deliver a range of novel combinations, new devices, and innovative product offerings to treat respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Our innovative precision approaches will ensure the right treatment for the right patient.
AstraZeneca’s respiratory portfolio includes asthma and COPD medicine Symbicort and asthma medicine Pulmicort, as well as COPD treatments, Eklira Genuair, Tudorza Pressair and Duaklir Genuair.
About Pearl Therapeutics
Pearl Therapeutics is a wholly owned subsidiary of AstraZeneca, following its acquisition in 2013. The company is focused on developing inhaled combination therapies for the treatment of highly prevalent respiratory diseases, including COPD and asthma. Pearl Therapeutics’ unique porous particle Co-Suspension Technology allows for the production of unique fixed-dose combinations of different classes of drugs at different concentrations in a single pressurised metered dose inhaler (pMDI) device. Fixed-dose combination therapies can simplify treatment for patients, improving the potential for convenience and compliance versus the use of separate inhalers. Non-adherence is a well-documented issue in COPD and is associated with detrimental effects on patient outcomes.
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca.com.
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1. Rabe K, PT003, a novel co-suspension MDI glycopyrronium/formoterol fixed-dose combination is superior to monocomponents in patients with COPD. Abstract number #PA4363. ERS 2015.
2. Miravitlles, M, Garcia Gil, E, Chuecos, F, Lamarca, R, Morning and nighttime symptoms in COPD and efficacy of aclidinium/formoterol in symptomatic vs asymptomatic patients. Oral presentation number #OA1968. ERS 2015.
3. Cunoosamy D et al., Demonstration of anti-inflammatory properties of an inhaled p38 inhibitor AZD7624. Abstract number #PA3904. ERS 2015.
4. Någård M et al., Prediction of human lung PK for AZD7624, an inhaled P38 inhibitor for the treatment of COPD. Abstract number #PA3950. ERS 201 5.
5. Patel N et al., AZD7624, an inhaled p38 inhibitor for COPD, attenuates lung and systemic inflammation after LPS Challenge in humans. Oral presentation #OA483. ERS 2015.
6. Clinical Trials PINNACLE 1. Available at: https://clinicaltrials.gov/ct2/show/NCT01854645 Last accessed September 2015.
7. Clinical Trials PINNACLE 2. Available at: https://clinicaltrials.gov/ct2/show/NCT01854658 Last accessed September 2015.
8. Clinical Trials PINNACLE 3. Available at: https://clinicaltrials.gov/ct2/show/NCT01970878 Last accessed September 2015.