AstraZeneca Announces Co-Commercialization Agreement with Daiichi Sankyo, Inc. for MOVANTIK
Mar 19 15
AstraZeneca announced a co-commercialization agreement with Daiichi Sankyo, Inc. for MOVANTIK (naloxegol) in the US, in line with the Company's strategy of delivering value through its own development and commercial capabilities as well as through external collaboration. MOVANTIK is a first-in-class once-daily oral peripherally-acting mu-opioid receptor antagonist (PAMORA) for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain. Under the terms of the agreement, Daiichi Sankyo Inc. will pay a $200 million up-front fee and subsequent sales-related payments of up to $625 million. AstraZeneca will be responsible for manufacturing, will book all sales and will make sales-related commission payments to Daiichi Sankyo, Inc. Both companies will be jointly responsible for commercial activities.
AstraZeneca PLC Announces Positive Top-Line Results from the Phase III PINNACLE Programme
Mar 18 15
AstraZeneca PLC announced positive top-line results from the Phase III PINNACLE programme, which included two pivotal 24-week studies (PINNACLE 1 and PINNACLE 2) to investigate the potential of PT003 to improve lung function in patients with Chronic Obstructive Pulmonary Disease (COPD). PT003 is 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 is the first LAMA/LABA combination to be delivered in a pressurised metered dose inhaler (pMDI) using the unique porous particle co-suspension technology developed by Pearl Therapeutics, which was acquired by AstraZeneca in 2013. The development programme also included assessment of the individual components of PT003 - glycopyrronium pMDI (PT001) and formoterol fumarate (PT005) pMDI. 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. In both the PINNACLE 1 and PINNACLE 2 studies, the primary objective was to assess benefits on lung function as measured by trough forced expiratory volume in one second (FEV1). PT003 demonstrated statistically significant improvements in trough FEV1 versus PT001, PT005 and placebo. Both PT001 and PT005 also demonstrated statistically significant improvements in trough FEV1 compared to placebo. In PINNACLE 1 and PINNACLE 2, the most common adverse events across all treatment arms, including placebo, were nasopharyngitis, upper respiratory tract infection, and dyspnea. The incidence of adverse events was generally similar across all treatment groups. The Phase III programme also included a 28-week extension study, PINNACLE 3, the safety information from which is not yet available. The company plans to file global regulatory applications for PT003 commencing in 2015. Data from the PINNACLE 1, 2, and 3 Phase III studies will be presented at a scientific meeting later in the year. 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. 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. In PINNACLE 1, open-label tiotropium was included as an active control. Both studies were conducted over 24 weeks in subjects with COPD. The primary objective of both studies was improvement in lung function as assessed by trough forced expiratory volume in one second (FEV1). 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 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 control.
AstraZeneca Announces Full Results from the PEGASUS-TIMI 54 Study
Mar 14 15
AstraZeneca announced full results from the PEGASUS-TIMI 54 study, a large-scale outcomes trial that investigated BRILINTA (ticagrelor) tablets plus low dose aspirin, compared to placebo plus low dose aspirin, for chronic secondary prevention of atherothrombotic events in patients who had experienced a heart attack one to three years prior to study enrollment. Key findings: Both 90mg and 60mg study doses of ticagrelor with aspirin significantly reduced the primary composite endpoint of cardiovascular (CV) death, myocardial infarction (MI) or stroke compared to placebo. As expected with an oral antiplatelet, TIMI Major Bleeding1, the study’s primary safety endpoint, was higher with both doses of ticagrelor plus aspirin compared to placebo plus aspirin. Importantly, the rates of intracranial hemorrhage (bleeding within the skull) and fatal bleeding were low and similar between study groups and the placebo arm. In this trial, both study doses of ticagrelor significantly reduced the primary endpoint of CV death, MI or stroke compared to placebo. The rates at 3 years were 7.85% in the ticagrelor 90mg arm, 7.77% in the ticagrelor 60mg arm, and 9.04% in the placebo arm (Hazard Ratio (HR) for ticagrelor 90mg vs placebo 0.85, 95% CI 0.75 – 0.96, P=0.0080; HR for ticagrelor 60mg vs placebo 0.84, 95% CI 0.74 – 0.95, P=0.0043). The effect of ticagrelor on each of the components of the primary endpoint was consistent. A numerical decrease in the secondary endpoints of cardiovascular death and all cause mortality was observed, but did not reach statistical significance. In addition, the primary efficacy endpoint of both doses of ticagrelor appeared consistent across major subgroups including age, sex, index MI type (STEMI/NSTEMI), time from qualifying MI, diabetes, aspirin dose, history of percutaneous intervention (angioplasty), and geographical region. As expected, TIMI Major bleeding was higher with both doses of ticagrelor compared to placebo, with rates at 3 years of 2.60% in the ticagrelor 90mg arm, 2.30% in the ticagrelor 60mg arm, and 1.06% in the placebo arm (HR for ticagrelor 90mg vs placebo 2.69, 95% CI 1.96 – 3.70, p<0.001; HR for ticagrelor 60mg vs placebo 2.32, 95% CI 1.68 – 3.21, p<0.001). However, the rates of fatal bleeding or intracranial hemorrhage were low and similar between treatment arms. Fatal bleeding rates at 3 years were 0.11% in the ticagrelor 90mg arm, 0.25% in the ticagrelor 60mg arm, and 0.26% in the placebo arm (HR for ticagrelor 90mg vs placebo 0.58, 95% CI 0.22 – 1.54, p=0.27; HR for ticagrelor 60mg vs placebo 1.00, 95% CI 0.44 – 2.27, p=1.00).
Intracranial hemorrhage rates at 3 years were 0.56% in the ticagrelor 90mg arm, 0.61% in the ticagrelor 60mg arm, and 0.47% in the placebo arm (HR for ticagrelor 90mg vs placebo 1.44, 95% CI 0.83 – 2.49, p=0.19; HR for ticagrelor 60mg vs placebo 1.33, 95% CI 0.77 – 2.31, p=0.31).
The PEGASUS-TIMI 54 study, AstraZeneca’s large outcomes trials involving more than 21,000 patients from over 1,100 sites in 31 countries, is part of the PARTHENON program. The PLATO study, involving over 18,000 patients, was the first study in the program and is the basis on which ticagrelor has been approved in over 100 countries and included in 12 major ACS treatment guidelines globally. Further ongoing PARTHENON studies are assessing ticagrelor for the prevention of cardiovascular events in patients with peripheral arterial disease, ischaemic stroke or transient ischaemic attack, and in patients with diabetes and coronary atherosclerosis.