REG - AstraZeneca PLC - AZN: FY16 and Q4 2016 Results <Origin Href="QuoteRef">AZN.L</Origin> - Part 2
02/02/2017 07:06
- Part 2: For the preceding part double click ID:nRSB8083Va
agreement with Amgen Inc. (Amgen)
HPV royalties 134
Other 336
Total 1,655
Operating Profit
Reported Operating Profit increased by 9% in the year to $4,902m. The Reported Operating Margin increased by three
percentage points to 21% of Total Revenue.
Core Operating Profit declined by 7% in the year to $6,721m. The Core Operating Margin was stable at 29% of Total Revenue.
Net Finance Expense
Reported Net Finance Expense increased by 37% in the year to $1,317m, reflecting an increase in Net Debt that was driven by
the acquisition of ZS Pharma and the majority investment in Acerta Pharma. Excluding the discount unwind on
acquisition-related liabilities, Core Net Finance Expense increased by 46% in the year to $661m.
Taxation
Excluding a one-off benefit of $453m following agreements between the Canadian tax authority and the UK and Swedish tax
authorities in respect of transfer pricing arrangements for the 13-year period from 2004-2016, the Reported and Core tax
rates for the year were 17% and 18% respectively. Including the impact of this benefit, the Reported and Core tax rates for
the year were 4% and 11% respectively. The cash tax paid for the year was $412m, which was 12% of Reported Profit Before
Tax and 7% of Core Profit Before Tax.
The Reported and Core tax rates in FY 2015 were 22% and 21% respectively when excluding a one-off tax benefit of $186m
following the agreement of US federal tax liabilities of open years up to 2008, other provision releases and the benefit of
the UK patent box. Including the impact of these benefits, the Reported and Core tax rates in FY 2015 were 8% and 16%
respectively.
Earnings Per Share (EPS)
Reported EPS of $2.77 in the year represented growth of 9%; this included a gain of $0.76 on the revaluation of
acquisition-related liabilities. Core EPS in the year declined by 5% to $4.31, driven by the same rate of decline in Total
Revenue. Both Reported and Core EPS in the year included a non-recurring benefit of $0.36, following the
previously-mentioned agreements between the Canadian tax authority and the UK and Swedish tax authorities.
Dividends
The Board has declared a second interim dividend of $1.90 per share (150.2 pence, 16.57 SEK) bringing the dividend per
share for the full year to $2.80 (218.9 pence, 24.38 SEK). The Board reaffirms its commitment to the Company's progressive
dividend policy.
For holders of the Company's American Depositary Shares (ADSs), the $1.90 per Ordinary Share equates to $0.95 per ADS. Two
ADSs equal one Ordinary Share.
Productivity
AstraZeneca's evolution and the changing shape of the business have enabled productivity improvements through the
implementation of restructuring initiatives. These included those announced on 29 April 2016. Restructuring charges of
$1,107m were incurred in the year. The Company remains on track to realise benefits and incur costs in line with prior
announcements.
Cash Flow And Balance Sheet
Cash Flow
The Company generated a net cash inflow from operating activities of $4,145m in the year, compared with $3,324m in the
comparative period. The increase reflected improved cash management performance and one-off tax refunds.
Net cash outflows from investing activities were $3,969m compared with $4,239m in the comparative period. The outflows
partly reflected the net cash outflow of $2,383m in relation to the majority investment in Acerta Pharma, as well as
$1,446m for the purchase of property, plant and equipment.
Net cash outflows from financing activities were $1,324m, incorporating $2,491m of new long-term loans, net of dividend
payments in the year of $3,561m. This compared to an inflow of $878m in the comparative period.
The cash payment of contingent consideration in respect of the Bristol-Myers Squibb Company share of the global Diabetes
alliance amounted to $242m in the year. The consideration is based on a tiered structure, whereby a higher royalty rate is
applied until a specified level of sales is achieved in the year; thereafter a lower rate is applied to the remaining sales
in the year and settled in the quarter following the application of the charge. From FY 2017 a single annual rate will be
applied.
Capital Expenditure
Capital expenditure amounted to $1,449m in the year, representing an increase of 3%; the majority of capital expenditure
was in maintenance. Investment in AstraZeneca's return to growth continued, with an element of capital expenditure split
between expansion of biologics manufacturing capacity and the impending completion of the R&D centre and global
headquarters in Cambridge, UK.
Debt and Capital Structure
At 31 December 2016, outstanding gross debt (interest-bearing loans and borrowings) was $16,808m
(31 December 2015: $15,053m). Of the gross debt outstanding at 31 December 2016, $2,307m was due within one year (31
December 2015: $916m). The Company's net debt position at 31 December 2016 was $10,657m (31 December 2015: $7,762m).
Shares in Issue
During the year, 1.1 million shares were issued in respect of share option exercises for consideration of $47m. The total
number of shares in issue as at 31 December 2016 was 1,265 million.
Capital Allocation
The Board's aim is to continue to strike a balance between the interests of the business, financial creditors and the
Company's shareholders. After providing for investment in the business, supporting the progressive dividend policy and
maintaining a strong, investment-grade credit rating, the Board will keep under review potential investment in immediately
earnings-accretive, value-enhancing opportunities. The Board reconfirms the continued suspension of the share repurchase
programme.
Sensitivity: Foreign-Exchange Rates
The Company provides the following currency sensitivity information:
Average Exchange Rates Versus USD Impact Of 5% Strengthening In Exchange Rate Versus USD ($m)2
Currency Primary Relevance FY 2016 YTD 20171 change % Total Revenue Core Operating Profit
EUR Product Sales 0.90 0.94 -4% +179 +123
JPY Product Sales 108.84 115.14 -5% +104 +71
CNY Product Sales 6.65 6.87 -3% +131 +74
SEK Costs 8.56 8.97 -5% +7 -98
GBP Costs 0.74 0.81 -9% +29 -131
Other3 +194 +124
1Based on average daily spot rates between 1st January and 30th January 2017 2Based on 2016 actual results at 2016 actual exchange rates3Other important currencies include AUD, BRL, CAD, KRW and RUB
Currency Hedging
AstraZeneca monitors the impact of adverse currency movements on a portfolio basis, recognising correlation effects. The
Company may hedge to protect against adverse impacts on cash flow over the short to medium term. As at 31 December 2016,
AstraZeneca had hedged 96% of forecast short-term currency exposure that arises between the booking and settlement dates on
Product Sales and non-local currency purchases.
Corporate And Business Development Update
______________________________________________________________________________________
The highlights of the Company's corporate and business development activities since the prior results announcement are
shown below:
a) Sale Of Small-Molecule Antibiotics Business
On 24 August 2016, the Company announced that it had entered into an agreement with Pfizer to sell the commercialisation
and development rights to its small-molecule antibiotics business and late-stage pipeline in most markets outside the US.
The transaction closed in the quarter. As AstraZeneca will not maintain a significant ongoing interest in the late-stage,
small-molecule antibiotics business, all payments were and will be reported as Other Operating Income in the Company's
financial statements. This includes the upfront payment of $550m and an unconditional payment of $175m in 2019 (both
recognised net of the carrying value of assets disposed and other costs to sell in 2016). The future payments include the
milestones of up to $250m, sales-related payments of up to $600m and recurring double-digit royalties on sales of Zavicefta
and ATM AVI.
b) Sale Of Respiratory Medicine Rhinocort Aqua (Nasal Spray)
On 7 October 2016, the Company announced that it had entered an agreement with Cilag, an affiliate of Johnson & Johnson,
for the divestment of the rights to Rhinocort Aqua outside the US. The transaction closed in the quarter.
c) Externalisation Of Beta-Blocker Medicine Toprol-XL
On 31 October 2016, the Company completed an agreement with Aralez Pharmaceuticals Trading DAC, a subsidiary of Aralez
Pharmaceuticals Inc., for the rights to branded and authorised generic Toprol-XL (metoprolol succinate) in the US.
AstraZeneca will retain a significant ongoing interest in Toprol-XL through retained ownership of the medicine in ROW
markets and product supply to Aralez. Therefore, the upfront payment of $175m, milestones and sales-related payments of up
to $48m and mid-teen percentage royalties was and will be reported as Externalisation Revenue in the Company's financial
statements.
d) Licensing Agreement: Monoclonal Antibody MEDI2070 (Crohn's Disease)
On 3 October 2016, the Company announced that MedImmune, its global biologics research and development arm, had entered a
licensing agreement with Allergan for the global rights to MEDI2070 (moderate-to-severe Crohn's disease). The transaction
closed in the quarter. AstraZeneca retained $148m of the upfront payment and will retain up to approximately $847m in
future potential milestones, as well as the tiered royalty payments of up to low double-digit percent, following payment to
Amgen under the provisions of the original agreement.
e) Externalisation Of Diabetes Medicines Bydureon And Byetta In China
On 10 October 2016, AstraZeneca entered a strategic collaboration with 3SBio for the rights to commercialise Bydureon and
Byetta in the Chinese market. The agreement allowed the Company to benefit from 3SBio's established expertise in injectable
medicines and also focus resources on AstraZeneca's oral diabetes franchise, including Onglyza, which is already marketed
in China, as well as Forxiga and Kombiglyze, which are anticipated to launch in China in 2017. The transaction closed in
the quarter.
Under the terms of the collaboration agreement, 3SBio made an upfront payment of $50m and will pay development milestones
of up to a further $50m for the exclusive rights to commercialise Bydureon and Byetta in the Chinese market (excluding Hong
Kong) for an initial period of 20 years. AstraZeneca will retain a significant ongoing interest in Bydureon and Byetta
through retained ownership of the medicines in other markets and will manufacture and supply these medicines to 3SBio for
an agreed purchase price.
f) MEDI1814 (Alzheimer's Disease)
AstraZeneca continues to collaborate with Lilly in the development of medicines for patients impacted by Alzheimer's
disease (AD). Building on the current collaboration for the BACE inhibitor, AZD3293, currently in two Phase III trials, the
companies are now also co-developing MEDI1814, an antibody selective for amyloid-beta 42 (Aβ42), which is currently in
Phase I development as a potential disease-modifying treatment for AD. The build-up of plaque in the brain containing the
peptide amyloid-beta (Aβ) is one of the pathological hallmarks of AD. MEDI1814 binds selectively to Aβ42, which is believed
to be a more toxic Aβ species. In pre-clinical models, MEDI1814 dose-dependently reduces levels of this peptide,
potentially slowing the progression of AD.
g) Senior Executive Team Changes
In January 2017, Leon Wang was appointed to the newly-created SET role of Executive Vice-President, Asia Pacific, with
responsibility for the Company's activities in China and Hong Kong, Asia Area, Australia and New Zealand. Leon joined
AstraZeneca China in 2013 as a Vice-President and became President in 2014. Under his leadership China became AstraZeneca's
second-largest market worldwide. Leon has twenty years of experience in the pharmaceutical industry.
As Executive Vice-President, International West, Mark Mallon retains responsibility for AstraZeneca's businesses in Russia,
Latin America, and the Middle East and Africa in addition to his role as EVP, Global Product and Portfolio Strategy, Global
Medical Affairs & Corporate Affairs.
It was announced in January 2017 that Luke Miels, formerly Executive Vice-President, Europe would leave AstraZeneca to take
up a senior position with a main competitor.
Research and Development Update
______________________________________________________________________________________
A comprehensive table with AstraZeneca's pipeline of medicines in human trials can be found later in this document.
Since the results announcement on 10 November 2016 (the period):
Regulatory Submission Acceptances 8 - durvalumab - bladder cancer (US)- Tagrisso - lung cancer (AURA3 trial) (US, EU)- Faslodex - breast cancer (1L) (US, EU)- roxadustat - anaemia (CN) (rolling submission)- benralizumab - severe, uncontrolled asthma (US, EU)
Other Key Developments 2 - Priority Review Designation: durvalumab (US)- Priority Review Designation: Tagrisso (US)
New Molecular Entities 12 Oncology- durvalumab* - multiple cancers- durva + treme - multiple cancers- acalabrutinib - blood cancers- moxetumomab pasudotox - leukaemia- selumetinib - thyroid cancer Cardiovascular & Metabolic Diseases- ZS-9* - hyperkalaemia- roxadustat* - anaemia Respiratory- benralizumab* - severe, uncontrolled asthma- tralokinumab - severe, uncontrolled asthma- PT010 - COPD Other- anifrolumab - lupus- AZD3293 - Alzheimer's disease
(NMEs) In Phase III Trials
Or Under Regulatory Review*#
Projects in clinical pipeline# 120
#As at 2 February 2017
ONCOLOGY
AstraZeneca has a deep-rooted heritage in Oncology and offers a growing portfolio of new medicines that has the potential
to transform patients' lives and the Company's future. At least six new Oncology medicines are expected to be launched
between 2014 and 2020, of which two have already been launched (Lynparza and Tagrisso). A broad pipeline of small molecules
and biologics is in development and the Company is committed to advancing Oncology as one of AstraZeneca's Growth Platforms
primarily focused on lung, ovarian, breast and blood cancers.
In addition to its own existing cancer medicine capabilities, the Company is actively pursuing innovative collaborations
and investments that are designed to accelerate the delivery of AstraZeneca's strategy, as illustrated by the Company's
majority investment in Acerta Pharma in haematology that closed in 2016.
At three recent medical meetings, ASH (American Society of Hematology), WCLC (World Conference on Lung Cancer) and the San
Antonio Breast Cancer Symposium, AstraZeneca highlighted its continued momentum in Oncology with a total of 50 abstracts,
including 15 oral presentations. Abstracts and presentations provided a comprehensive update on recent data from Faslodex,
Iressa, Tagrisso and the Company's emerging presence in blood cancers, through acalabrutinib.
a) Faslodex (breast cancer)
During the period, the Company received regulatory submission acceptances for Faslodex in 1st-line metastatic breast cancer
in the US and the EU. The submissions were based on the Phase III FALCON trial that compared Faslodex 500mg to Arimidex 1mg
for the treatment of locally-advanced or metastatic breast cancer, in post-menopausal women who have not had prior hormonal
treatment for hormone receptor-positive breast cancer. Faslodex demonstrated superiority compared with Arimidex and met its
primary endpoint of extended progression-free survival (PFS).
b) Tagrisso (lung cancer)
In December 2016, data from the AURA3 trial were presented at WCLC. AURA3 was the first randomised and controlled trial for
Tagrisso and tested the medicine in 2nd-line treatment of patients with epidermal growth factor receptor (EGFR) T790M
mutation-positive locally-advanced or metastatic NSCLC against standard-of-care (SoC) platinum-based doublet chemotherapy.
The trial showed that Tagrisso significantly improved PFS by 5.7 months with a hazard ratio of 0.30 (equal to a risk
reduction of 70%).
Additionally, in the 34% of patients with central nervous system (CNS) metastases at baseline, PFS was also significantly
greater (4.3 months, hazard ratio 0.32) with Tagrisso. The medicine's ability to provide benefit in patients with CNS
metastases is encouraging and Tagrisso continues to be tested in the BLOOM trial. Based on results from AURA3, regulatory
submissions were made in the US and EU during the period; acceptances were received on both submissions and Priority Review
Designation was obtained in the US.
c) Durvalumab (multiple cancers)
In December 2016, AstraZeneca received FDA acceptance with Priority Review status of the Biologics License Application
(BLA) for durvalumab in patients with locally-advanced or metastatic urothelial carcinoma, whose disease has progressed
during or after one standard platinum-based regimen. This acceptance was based on the results of the urothelial cancer
cohort of Study 1108 and follows the FDA's Breakthrough Therapy Designation for durvalumab in bladder cancer in February
2016. The Prescription Drug User Fee Act (PDUFA) date is in the second quarter of 2017.
The Company is also advancing durvalumab alone and in combination with tremelimumab in bladder cancer.
METASTATIC UROTHELIAL BLADDER CANCER Name Phase Line of Treatment Population Design Timelines Status Combination therapy DANUBE III 1st Line Cisplatin chemo-therapy- eligible/ineligible bladder cancer durvalumab, durva + treme vs SoC chemotherapy FPD1 Q4 2015 First data anticipated 2018 Ongoing The Company continues to advance multiple monotherapy trials of durvalumab and combination trials of durvalumab with tremelimumab and other potential new medicines in Immuno-Oncology (IO). An update on key
AstraZeneca-sponsored ongoing trials with durvalumab outside bladder cancer is provided below: LUNG CANCER Name Phase Line of Treatment Population Design Timelines Status Monotherapy ADJUVANT2 III N/A Stage Ib-IIIa NSCLC durvalumab vs placebo FPD Q1 2015 First data anticipated 2020 Ongoing PACIFIC III N/A Stage III unresectable NSCLC durvalumab vs placebo FPD Q2 2014 LPCD3 Q2 2016 First data anticipated H2 2017 Recruitment completed PEARL III 1st line NSCLC (Asia) durvalumab vs SoC chemotherapy First data
anticipated 2020 Initiating Combination therapy MYSTIC III 1st line NSCLC durvalumab, durva + treme vs SoC chemotherapy FPD Q3 2015
LPCD Q3 2016 First data anticipated mid-2017 Recruitment completed NEPTUNE III 1st line NSCLC durva + treme vs SoC chemotherapy FPD Q4 2015 First data anticipated 2018 Ongoing - III 1st line NSCLC durvalumab + chemotherapy +/- tremelimumab - Ongoing in safety lead-in Phase I/II trial ARCTIC III 3rd line PD-L1 neg. NSCLC durvalumab, tremelimumab, durva + treme vs SoC chemotherapy FPD Q2 2015 LPCD Q3 2016 First data anticipated H1 2017 Recruitment completed CASPIAN III 1st line Small-cell lung cancer
durvalumab + SoC, durva + treme + SoC vs SoC chemotherapy - Initiating 1 FPD = First Patient Dosed2 Conducted by the National Cancer Institute of Canada3 LPCD = Last Patient Commenced Dosing On 17 January 2017, the Company provided an update on its late-stage IO clinical-development programme in 1st-line NSCLC, including a refinement of the Phase III MYSTIC trial. The trial was initially designed to assess the benefit of durvalumab monotherapy and durvalumab and tremelimumab (durva + treme) combination
therapy versus SoC chemotherapy, focused on PFS. The MYSTIC trial will now assess PFS and overall survival (OS) endpoints in patients with PDL1-expressing tumours for both durvalumab monotherapy and the combination of durva + treme, as well as in 'all comers' for the combination of durva + treme, versus SoC chemotherapy. While the focus remains on exploring the benefit of durva + treme as combination therapy, the Company has updated the endpoints of the MYSTIC trial to include OS and PFS in durvalumab
monotherapy. This is based on recent internal and external data, including durvalumab's strong efficacy in monotherapy presented at recent medical meetings, as well as significant opportunities in the competitive landscape. The estimated primary completion date was updated to reflect both an increase in patient recruitment (as reported in February 2016 with the inclusion of OS as a co-primary endpoint) and the event-based nature of the trial. As a result, the Company anticipates MYSTIC PFS data in mid-2017
and final OS data, at the latest, in 2018. MYSTIC also includes several undisclosed interim analyses for OS. Additionally, the ongoing Phase III NEPTUNE trial will be expanded with local patients to support regulatory submission of durva + treme combination therapy in China for 1st-line NSCLC patients, without delaying the anticipated OS data readout in 2018 from the global cohort, which is approaching full recruitment. The Company has also initiated the new Phase III PEARL trial of durvalumab monotherapy
versus SoC chemotherapy in 1st-line NSCLC patients, whose tumours express PD-L1. The PEARL trial focuses on Asian countries, primarily China, due to the prevalence of NSCLC in the region. At WCLC, AstraZeneca presented safety findings from the safety lead-in Phase Ib trial of durvalumab with or without tremelimumab in combination with doublet chemotherapy. The conclusion of this trial was that in a PD-L1 unselected patient population, durvalumab and tremelimumab can be safely combined with full doses of
pemetrexed/cisplatin chemotherapy. METASTATIC OR RECURRENT HEAD AND NECK CANCER Name Phase Line of Treatment Population Design Timelines Status Combination therapy KESTREL III 1st line HNSCC* durvalumab, durva + treme vs SoC FPD Q4 2015 First data anticipated H2 2017 Ongoing EAGLE III 2nd line HNSCC durvalumab, durva + treme vs SoC FPD Q4 2015 First data anticipated 2018 Ongoing
METASTATIC UROTHELIAL BLADDER CANCER
Name
Phase
Line of Treatment
Population
Design
Timelines
Status
Combination therapy
DANUBE
III
1st Line
Cisplatin chemo-therapy- eligible/ineligible bladder cancer
durvalumab, durva + treme vs SoC chemotherapy
FPD1 Q4 2015 First data anticipated 2018
Ongoing
The Company continues to advance multiple monotherapy trials of durvalumab and combination trials of durvalumab with
tremelimumab and other potential new medicines in Immuno-Oncology (IO). An update on key AstraZeneca-sponsored ongoing
trials with durvalumab outside bladder cancer is provided below:
Monotherapy
ADJUVANT2 III N/A Stage Ib-IIIa NSCLC durvalumab vs placebo FPD Q1 2015 First data anticipated 2020 Ongoing
PACIFIC III N/A Stage III unresectable NSCLC durvalumab vs placebo FPD Q2 2014 LPCD3 Q2 2016 First data anticipated H2 2017 Recruitment completed
PEARL III 1st line NSCLC (Asia) durvalumab vs SoC chemotherapy First data anticipated 2020 Initiating
Combination therapy
MYSTIC III 1st line NSCLC durvalumab, durva + treme vs SoC chemotherapy FPD Q3 2015 Recruitment completed
LPCD Q3 2016 First data anticipated mid-2017
NEPTUNE III 1st line NSCLC durva + treme vs SoC chemotherapy FPD Q4 2015 First data anticipated 2018 Ongoing
- III 1st line NSCLC durvalumab + chemotherapy +/- tremelimumab - Ongoing in safety lead-in Phase I/II trial
ARCTIC III 3rd line PD-L1 neg. NSCLC durvalumab, tremelimumab, durva + treme vs SoC chemotherapy FPD Q2 2015 LPCD Q3 2016 First data anticipated H1 2017 Recruitment completed
CASPIAN III 1st line Small-cell lung cancer durvalumab + SoC, durva + treme + SoC vs SoC chemotherapy - Initiating
FPD Q2 2015 LPCD Q3 2016 First data anticipated H1 2017
Recruitment completed
CASPIAN
III
1st line
Small-cell lung cancer
durvalumab + SoC, durva + treme + SoC vs SoC chemotherapy
-
Initiating
1 FPD = First Patient Dosed2 Conducted by the National Cancer Institute of Canada3 LPCD = Last Patient Commenced Dosing On
17 January 2017, the Company provided an update on its late-stage IO clinical-development programme in 1st-line NSCLC,
including a refinement of the Phase III MYSTIC trial. The trial was initially designed to assess the benefit of durvalumab
monotherapy and durvalumab and tremelimumab (durva + treme) combination therapy versus SoC chemotherapy, focused on PFS.
The MYSTIC trial will now assess PFS and overall survival (OS) endpoints in patients with PDL1-expressing tumours for both
durvalumab monotherapy and the combination of durva + treme, as well as in 'all comers' for the combination of durva +
treme, versus SoC chemotherapy. While the focus remains on exploring the benefit of durva + treme as combination therapy,
the Company has updated the endpoints of the MYSTIC trial to include OS and PFS in durvalumab monotherapy. This is based on
recent internal and external data, including durvalumab's strong efficacy in monotherapy presented at recent medical
meetings, as well as significant opportunities in the competitive landscape. The estimated primary completion date was
updated to reflect both an increase in patient recruitment (as reported in February 2016 with the inclusion of OS as a
co-primary endpoint) and the event-based nature of the trial. As a result, the Company anticipates MYSTIC PFS data in
mid-2017 and final OS data, at the latest, in 2018. MYSTIC also includes several undisclosed interim analyses for OS.
Additionally, the ongoing Phase III NEPTUNE trial will be expanded with local patients to support regulatory submission of
durva + treme combination therapy in China for 1st-line NSCLC patients, without delaying the anticipated OS data readout in
2018 from the global cohort, which is approaching full recruitment. The Company has also initiated the new Phase III PEARL
trial of durvalumab monotherapy versus SoC chemotherapy in 1st-line NSCLC patients, whose tumours express PD-L1. The PEARL
trial focuses on Asian countries, primarily China, due to the prevalence of NSCLC in the region. At WCLC, AstraZeneca
presented safety findings from the safety lead-in Phase Ib trial of durvalumab with or without tremelimumab in combination
with doublet chemotherapy. The conclusion of this trial was that in a PD-L1 unselected patient population, durvalumab and
tremelimumab can be safely combined with full doses of pemetrexed/cisplatin chemotherapy.
Combination therapy
KESTREL III 1st line HNSCC* durvalumab, durva + treme vs SoC FPD Q4 2015 First data anticipated H2 2017 Ongoing
EAGLE III 2nd line HNSCC durvalumab, durva + treme vs SoC FPD Q4 2015 First data anticipated 2018 Ongoing
durvalumab, durva + treme vs SoC
FPD Q4 2015 First data anticipated 2018
Ongoing
*Head and Neck Squamous Cell Carcinoma
As communicated on 15 December 2016, the Company has reviewed data from the CONDOR trial, a randomised, but non-controlled
Phase II trial in 2nd-line PDL1-negative HNSCC patients. While the data show efficacy and safety of the experimental
medicines, AstraZeneca does not believe that a non-controlled trial can facilitate a regulatory submission for accelerated
approval in a setting where a PD1-targeted medicine was approved during 2016, based on an OS benefit in all-comers.
On 22 November 2016, AstraZeneca announced that the FDA had lifted the partial clinical hold on the enrolment of new
patients with HNSCC for clinical trials of durvalumab as monotherapy and in combination with tremelimumab or other
potential new medicines. The partial clinical hold on new patient enrolment was communicated on 27 October 2016, after
preliminary findings from ongoing clinical trials related specifically to HNSCC. The FDA lifted the hold following a review
of the comprehensive analysis provided by AstraZeneca of bleeding events that were observed as part of the routine safety
monitoring of the Phase III KESTREL and EAGLE trials.
d) Acalabrutinib (blood cancers)
Less than a year after announcing a majority investment in Acerta Pharma, AstraZeneca provided new clinical data on
acalabrutinib, a highly-selective, potent Bruton tyrosine-kinase (BTK) inhibitor in Phase III development for B-cell
malignancies. At the 2016 ASH annual meeting, two oral presentations were shared on acalabrutinib, in patients with
Richter's transformation and in patients with ibrutinib intolerance, both Phase I/II trials.
In patients with Richter's transformation, acalabrutinib monotherapy produced a partial or complete response in 38% of
patients, with a median time on treatment of 3.4 months. In 21 Richter-transformation patients evaluable for efficacy
measures in the trial, median PFS was 2.1 months and the median duration of response was 5.2 months. Acalabrutinib
monotherapy demonstrated a tolerable safety profile in patients with Richter's transformation and these data suggested that
further investigation, in combination with immunotherapy or other targeted therapies, is warranted.
Acalabrutinib was well tolerated in ibrutinib-intolerant patients, with a total of 12 of 33 (36%) patients experiencing
adverse event (AE) recurrence, most of which reduced or had the same severity as before; no patients discontinued treatment
because of a recurrent AE. This safety profile was coupled with promising activity (objective response rate of 79%) and
response duration (81% of responding patients had a duration of response ≥12 months).
CARDIOVASCULAR & METABOLIC DISEASES
This therapy area includes a broad type-2 diabetes portfolio, differentiated devices and unique small and large-molecule
programmes to reduce morbidity, mortality and organ damage across CV disease, diabetes and chronic kidney disease (CKD)
indications.
a) Bydureon (type-2 diabetes)
During the period, the DURATION-7 trial met its primary endpoint of a reduction in blood glucose (HbA1c) at 28 weeks as
well as key secondary endpoints. No new safety findings were observed and the overall rates of AEs and serious AEs were low
in both groups.
DURATION-7 was a multi-centre, randomised, double-blind, placebo-controlled, parallel group, Phase III trial that evaluated
the safety and efficacy of once-weekly Bydureon therapy added to titrated basal insulin glargine, compared with placebo
added to titrated basal insulin glargine, in patients with type-2 diabetes who have inadequate glycaemic control on basal
insulin glargine with or without metformin.
b) Type-2 diabetes medicines in CV outcomes trials
As the field of type-2 diabetes medicines evolves, with multiple outcomes trials producing data, AstraZeneca continues to
assess both Farxiga and Bydureon for potential long-term CV benefits. Two significant type-2 diabetes outcomes trials are
progressing:
Medicine Trial Mode of Action Number of Patients Primary Endpoint Timeline
Bydureon EXSCEL GLP-1 agonist ~14,000 Time to first occurrence of CV death, non-fatal MI or non-fatal stroke Latest 2018(final analysis)
Farxiga DECLARE SGLT2 inhibitor ~17,000* Time to first occurrence of CV death, non-fatal MI or non-fatal stroke Latest 2019(final analysis)
*Includes ~10,000 patients who have had no prior index event (primary prevention) and ~7,000 patients who have suffered an
index event (secondary prevention).
c) Roxadustat (anaemia)
Roxadustat is a potential first-in-class oral HIF-PH inhibitor in Phase III development for the treatment of anaemia in CKD
patients. AstraZeneca, FibroGen, Inc. (FibroGen) and Astellas Pharma Inc. are jointly undertaking an extensive worldwide
Phase III trial programme, enrolling more than 8,000 patients.
In addition to evaluating efficacy, the US/global programme is designed to demonstrate the CV safety of roxadustat in
comparison to epoetin alfa in dialysis patients (based on data pooled from four clinical trials) and in comparison to
placebo in non-dialysis patients (based on data pooled from three clinical trials). AstraZeneca and FibroGen anticipate
data readout and US regulatory submission in 2018.
FibroGen is responsible for development and regulatory activities in China, and recently announced that the submission
process had initiated and is expected to complete in the second or third quarter of 2017.
Additionally, on 30 January 2017, FibroGen reported positive results from two Phase III clinical trials of roxadustat in
China. The two Phase III clinical trials evaluated roxadustat for anaemia in CKD in patients on dialysis and not on
dialysis. Both Phase III trials met their primary efficacy endpoints, confirming earlier results. Initial analysis suggests
that adverse events were consistent with previous clinical trials of roxadustat in the CKD patient population.
RESPIRATORY
AstraZeneca's Respiratory portfolio is aimed at transforming the treatment of asthma and COPD through combination inhaled
therapies, biologics for the unmet medical needs of specific patient populations and an early pipeline focused on disease
modification. The growing range of medicines includes up to four launches between 2017 and 2020. The capability in
inhalation technology spans both pMDIs and dry-powder inhalers to serve patient needs, as well as the innovative Aerosphere
co-suspension delivery technology, a focus of AstraZeneca's future-platform development for respiratory-disease combination
therapies.
a) Symbicort (asthma, COPD)
During the period, the Company received EU approval for Symbicort SMART (Symbicort Maintenance And Reliever Therapy) for
adolescent asthma patients (aged 12 to <18 years). The SMART regimen for adolescents is the same as for adult patients,
with a daily maintenance dose of SymbicortTurbuhaler plus additional doses as needed in response to symptoms. Symbicort
SMART is a key component of the Company's commitment to 'patient-adjusted therapy' in treating asthma.
On 26 January 2017, AstraZeneca announced that the FDA had granted six months of paediatric exclusivity for Symbicort,
based on the evaluation of trials conducted in children with asthma aged six up to 12 years.
b) Benralizumab (severe, uncontrolled asthma)
During the period, AstraZeneca announced that the FDA accepted a BLA for benralizumab, an anti-eosinophil monoclonal
antibody (mAb), with a PDUFA date anticipated in Q4 2017. The Company also announced that the European Medicines Agency
accepted the Marketing Authorisation Application (MAA) for benralizumab.
The BLA and MAA submissions, for the treatment of patients with severe, uncontrolled asthma with an eosinophilic phenotype,
were based on the results of the pivotal Phase III trials, SIROCCO and CALIMA, that demonstrated that adding benralizumab
to SoC significantly reduced exacerbations and improved lung function and asthma symptoms. To date, five positive Phase III
trials (BISE, SIROCCO, CALIMA, GREGALE and ZONDA) have supported the efficacy and safety profile of benralizumab.
ASTRAZENECA DEVELOPMENT PIPELINE 31 DECEMBER 2016
AstraZeneca-sponsored or -directed trials
Phase III / Pivotal Phase II / Registration
New Molecular Entities (NMEs) and significant additional indications
Regulatory submission dates shown for assets in Phase III and beyond. As disclosure of compound information is balanced by
the business need to maintain confidentiality, information in relation to some compounds listed here has not been disclosed
at this time.
Oncology
TagrissoAURA, AURA2, (AURA17 Asia regional) EGFR inhibitor ≥2nd-line advanced EGFRm T790M NSCLC Launched(Breakthrough Therapy, Priority Review, Orphan drug) Launched (Accelerated assessment) Launched Accepted
TagrissoAURA3 EGFR inhibitor ≥2nd-line advanced EGFRm T790M NSCLC Accepted(Priority Review) Accepted
durvalumab# PD-L1 mAb ≥2nd-line advanced bladder cancer Accepted(Breakthrough Therapy & Priority Review)
acalabrutinib# BTK inhibitor B-cell malignancy Q1 2015 H1 2017(Orphan drug)
acalabrutinib# BTK inhibitor 1st-line CLL Q3 2015 2020(Orphan drug) 2020(Orphan drug)
acalabrutinib# BTK inhibitor r/r CLL, high risk Q4 2015 2020(Orphan drug) 2020(Orphan drug)
selumetinib MEK inhibitor differentiated thyroid cancer Q3 2013 2018(Orphan drug) 2018
ASTRA
moxetumomab pasudotox#PLAIT anti-CD22 recombinant hairy cell leukaemia Q2 2013 2018 (Orphan drug)
immunotoxin
durvalumab#PACIFIC PD-L1 mAb stage III NSCLC Q2 2014 H2 2017 H2 2017 H2 2017
durvalumab# +tremelimumab PD-L1 mAb + CTLA-4 mAb 3rd-line NSCLC Q2 2015 H2 2017 H2 2017 H2 2017
ARCTIC
durvalumab# + tremelimumabMYSTIC PD-L1 mAb + CTLA-4 mAb 1st-line NSCLC Q3 2015 H2 2017 H2 2017 H2 2017
durvalumab# + tremelimumabNEPTUNE PD-L1 mAb + CTLA-4 mAb 1st-line NSCLC Q4 2015 2019 2019 2019 2020
durvalumab# + tremelimumab PD-L1 mAb + CTLA-4 mAb 1st-line HNSCC Q4 2015 2018 2018 2018
KESTREL
durvalumab# + tremelimumab PD-L1 mAb + CTLA-4 mAb 2nd-line HNSCC Q4 2015 2018 2018 2018
EAGLE
durvalumab# + tremelimumabDANUBE PD-L1 mAb + CTLA-4 mAb 1st-line bladder cancer Q4 2015 2018 2018 2018
Cardiovascular & Metabolic Diseases
Brilinta1 P2Y12 receptor antagonist arterial thrombosis Launched Launched Approved Launched
Farxiga2 SGLT2 inhibitor type-2 diabetes Launched Launched Launched Accepted
Epanova# omega-3 carboxylic acids severe hypertriglyceridemia Approved 2018
ZS-9 (sodium zirconium cyclosilicate) potassium binder hyperkalaemia Accepted Accepted
roxadustat# OLYMPUS (US) ROCKIES (US) hypoxia-inducible factor prolyl hydroxylase inhibitor anaemia in CKD/ESRD Q3 2014 2018 Initiated3
Respiratory
Bevespi Aerosphere (PT003) LABA/LAMA COPD Launched4 H1 2017 2018 2018
benralizumab#CALIMA SIROCCO ZONDABISEBORAGREGALE IL-5R mAb severe asthma Accepted Accepted H1 2017 2020
benralizumab#TERRANOVA GALATHEA IL-5R mAb COPD Q3 2014 2018 2018 2019
PT010 LABA/LAMA/ICS COPD Q3 2015 2018 2018 2018 2019
tralokinumabSTRATOS 1,2TROPOSMESOS IL-13 mAb severe asthma Q3 2014 2018 2018 2018
Other
anifrolumab# TULIP IFN-alphaR mAb systemic lupus erythematosus Q3 2015 2019(Fast Track) 2019 2019
AZD3293#AMARANTHDAYBREAK-ALZ beta-secretase inhibitor Alzheimer's disease Q2 2016 2020(Fast Track) 2020 2020
2019
2019
AZD3293#AMARANTHDAYBREAK-ALZ
beta-secretase inhibitor
Alzheimer's disease
Q2 2016
2020(Fast Track)
2020
2020
¶ Registrational Phase IItrial
# Collaboration
1 Brilinta in the US and Japan; Brilique in ROW
2 Farxiga in the US; Forxiga in ROW
3 Rolling New Drug Application (NDA) regulatory submission initiated in Q4 2016
4 Bevespi Aerosphere (glycopyrrolate and formoterol fumarate) inhalation aerosol was launched commercially in the US in
January 2017
Phases I and II
NMEs and significant additional indications
Oncology
durvalumab# PD-L1 mAb solid tumours II Q3 2014
durvalumab# + tremelimumab PD-L1 mAb + CTLA-4 mAb Hepatocellular carcinoma (liver cancer) II Q4 2016
durvalumab# + tremelimumab PD-L1 mAb + CTLA-4 mAb gastric cancer II Q2 2015
durvalumab# + AZD5069 PD-L1 mAb + CXCR2 HNSCC II Q3 2015
durvalumab# + AZD9150# PD-L1 mAb + STAT3 inhibitor
durvalumab# + dabrafenib + trametinib PD-L1 mAb+ BRAF inhibitor + MEK inhibitor melanoma II Q1 2014
durvalumab# + AZD1775# PD-L1 mAb + Wee1 inhibitor solid tumours I Q4 2015
durvalumab# + MEDI0680 PD-L1 mAb + PD-1 mAb solid tumours I Q3 2016
durvalumab# or durvalumab# + (tremelimumab or AZD9150#) PD-L1 mAb or PD-L1 mAb + (CTLA-4 mAb or STAT3 inhibitor) diffuse large B-cell lymphoma I Q3 2016
durvalumab#+ Iressa PD-L1 mAb+ EGFR inhibitor NSCLC I Q2 2014
durvalumab# + MEDI0562# PD-L1 mAb + humanised OX40 agonist solid tumours I Q2 2016
durvalumab# + MEDI9447 PD-L1 mAb + CD73 mAb solid tumours I Q1 2016
durvalumab# + monalizumab PD-L1 mAb + NKG2a mAb solid tumours I Q1 2016
durvalumab# + selumetinib PD-L1 mAb + MEK inhibitor solid tumours I Q4 2015
durvalumab# + tremelimumab PD-L1 mAb + CTLA-4 mAb solid tumours I Q4 2013
tremelimumab + MEDI0562# CTLA-4 mAb + humanised OX40 agonist solid tumours I Q2 2016
Lynparza + AZD6738 PARP inhibitor + ATR inhibitor gastric cancer II Q3 2016
Lynparza + AZD1775# PARP inhibitor + Wee1 inhibitor solid tumours I Q3 2015
savolitinib# MET inhibitor papillary renal cell carcinoma II Q2 2014
Tagrisso + (selumetinib# or savolitinib#)TATTON EGFR inhibitor + (MEK inhibitor or MET inhibitor) advanced EGFRm NSCLC II Q2 2016
Tagrisso BLOOM EGFR inhibitor CNS metastases in advanced EGFRm NSCLC II Q4 2015
AZD1775#+ chemotherapy Wee1 inhibitor + chemotherapy ovarian cancer II Q4 2012
AZD1775# Wee1 inhibitor solid tumours II Q1 2016
vistusertib (AZD2014) mTOR inhibitor solid tumours II Q1 2013
AZD5363# AKT inhibitor breast cancer II Q1 2014
AZD4547 FGFR inhibitor solid tumours II Q4 2011
MEDI-573# IGF mAb metastatic breast cancer II Q2 2012
AZD0156 ATM inhibitor solid tumours I Q4 2015
AZD2811# Aurora B inhibitor solid tumours I Q4 2015
AZD4635 A2aR inhibitor solid tumours I Q2 2016
AZD6738 ATR inhibitor solid tumours I Q4 2013
AZD8186 PI3k inhibitor solid tumours I Q2 2013
AZD9150# STAT3 inhibitor
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