REG - AstraZeneca PLC - AstraZeneca PLC - H1 2017 Results <Origin Href="QuoteRef">AZN.L</Origin> - Part 2
27/07/2017 07:09
- Part 2: For the preceding part double click ID:nRSa2225Ma
the Crestor and
Seroquel XR loss of exclusivity in the US on Product Sales. Excluding the impact of Externalisation Revenue, the Reported
Gross Profit Margin was stable (down one percentage point at CER) at 81.5%.
Core Gross Profit declined by 10% (9% at CER) to $8,751m and, excluding the impact of Externalisation Revenue, the Core
Gross Profit margin increased by one percentage point to 83.0% (stable at CER), reflecting the mix of sales, the growing
influence of specialty-care medicines, the impact of losses of exclusivity and the resilience of some legacy medicines in
established markets.
Operating Expenses: R&D
Reported R&D costs declined by 5% (1% at CER) to $2,802m, with the Company continuing to focus on resource prioritisation
and cost discipline. Core R&D costs declined by 7% (4% at CER) to $2,617m. Core R&D costs over the full year are expected
to be broadly in line with those in FY 2016.
Operating Expenses: SG&A
Reported SG&A costs declined by 17% (15% at CER) to $4,658m, reflecting the evolving shape of the business. Core SG&A costs
declined by 12% (9% at CER) to $3,728m. Core SG&A costs over the full year are not expected to decline by the extent seen
in the first half.
The Company has continued to consolidate its operations used by multiple parts of the business. It is committed to driving
simplification and standardisation through centralisation in shared services of back-office and some middle-office
activities that are currently performed in various enabling units, including Finance, HR, Procurement and IT. Instead of
operating numerous shared-service centres and managing outsourced vendors independently, the recently-launched Global
Business Services organisation will, over time, provide integration of governance, locations and business practices to all
shared services and outsourcing activities across AstraZeneca.
Other Operating Income and Expense
Where AstraZeneca does not retain a significant ongoing interest in medicines or potential new medicines, income from
disposal transactions is reported within Other Operating Income and Expense in the Company's financial statements.
Reported Other Operating Income and Expense increased by 97% (101% at CER) to $839m and included:
· $291m resulting from the sale of rights to Seloken in Europe to Recordati S.p.A (Recordati)
· $165m resulting from the sale of the global rights to Zomig outside Japan to the Grünenthal Group (Grünenthal)
· $161m of gains recognised on the sale of short-term investments
· A milestone receipt of $50m in relation to the disposal of Zavicefta (ceftazidime and avibactam) to Pfizer Inc.
· Income from the monetisation of an asset related to a previously-partnered legacy medicine
Core Other Operating Income and Expense increased by 105% (108% at CER) to $958m, with the difference to Reported Other
Operating Income and Expense primarily driven by a restructuring charge taken against land and buildings.
Operating Profit
Reported Operating Profit increased by 37% (22% at CER) to $1,842m. The Reported Operating Margin increased by six
percentage points (four percentage points at CER) at 18% of Total Revenue. Core Operating Profit increased by 7% (3% at
CER) to $3,215m. The Core Operating Margin increased by five percentage points (four percentage points at CER) to 31% of
Total Revenue.
Net Finance Expense
Reported Net Finance Expense increased by 17% to $742m, primarily reflecting an adverse foreign-exchange impact caused by
the strengthening of sterling and euro against the dollar. Reported Net Finance Expense increased by 3% at CER, reflecting
the impact of a bond issuance in the half and an increase in Net Debt that was driven by the majority investment in Acerta
Pharma in February 2016. Excluding the discount unwind on acquisition-related liabilities and the adverse foreign-exchange
impact, Core Net Finance Expense increased by 13% (7% at CER) to $357m.
Taxation
The Reported and Core tax rates for the half were 11% and 19% respectively. The Reported tax rate was lower than the 2017
UK Corporation Tax Rate of 19.25%, mainly due to the impact of tax settlements and non-taxable fair value adjustments
relating to contingent consideration on business combinations. The Core tax rate was lower than the aforementioned 2017 UK
Corporation Tax Rate, mainly due to the impact of tax settlements.
The net cash tax paid for the half was $336m, representing 31% of Reported Profit Before Tax and 12% of Core Profit Before
Tax. Reduced net tax cash payments primarily reflected refunds following a previously-disclosed agreement of
inter-government transfer pricing agreements. The Reported and Core tax rates for the comparative period were 14% and 17%,
respectively.
Earnings Per Share (EPS)
Reported EPS of $0.80 represented an increase of 58% (41% at CER). Core EPS grew by 5% (1% at CER) to $1.86. The Core
performance was driven by continued progress on cost control and an increase in Other Operating Income and Expense, partly
offset by a decline in Total Revenue.
Dividends
The Board has recommended an unchanged first interim dividend of $0.90 (68.9 pence, 7.40 SEK) per Ordinary Share.
Cash Flow and Balance Sheet
Cash Flow
The Company generated a net cash inflow from operating activities of $338m in the half, compared with $1,374m in the
comparative period. The reduction reflected a lower profit, after deductions of gains on disposal of intangible assets, as
well as a higher increase in working capital and short-term provisions due to a significant increase in the level of debt
factoring in the comparative period.
Net cash outflows from investing activities were $351m in the half compared with $3,948m in the comparative period. The
prior-period outflow primarily reflected the upfront payment as part of the majority investment in Acerta Pharma.
The cash payment of contingent consideration in respect of the Bristol-Myers Squibb Company share of the global Diabetes
alliance amounted to $185m in the half, comprising a $100m milestone payment in respect of Qtern and royalty payments.
Net cash inflows from financing activities were $146m in the half compared to outflows of $6m in the comparative period.
Capital Expenditure
Capital expenditure amounted to $549m in the half, which included investment in the new global headquarters in Cambridge,
UK, as well as strategic manufacturing capacity in the UK, the US, Sweden and China.
Debt and Capital Structure
At 30 June 2017, outstanding gross debt (interest-bearing loans and borrowings) was $19,725m (30 June 2016: $17,579m). Of
the gross debt outstanding at 30 June 2017, $2,933m was due within one year (30 June 2016: $1,060m). The Company's net debt
position at 30 June 2017 was $13,012m (30 June 2016: $12,734m).
On 5 June 2017, the Company announced that it had priced a global bond offering totalling $2bn; the offering closed on 12
June 2017. The intended use of the net proceeds of the issue was for general corporate purposes, including the potential
refinancing of existing indebtedness. The transaction consisted of the following three tranches:
· $1bn of five-year fixed-rate notes with a coupon of 2.375%
· $0.75bn of 10-year fixed-rate notes with a coupon of 3.125%
· $0.25bn of five-year floating-rate notes
Capital Allocation
The Board's aim is to continue to strike a balance between the interests of the business, financial creditors and the
Company's shareholders. After providing for investment in the business, supporting the progressive dividend policy and
maintaining a strong, investment-grade credit rating, the Board will keep under review potential investment in immediately
earnings-accretive, value-enhancing opportunities.
Foreign-Exchange Rates
Sensitivity
The Company provides the following currency sensitivity information:
Average Exchange Rates Versus USD Impact Of 5% Strengthening In Exchange Rate Versus USD ($m)1
Currency Primary Relevance FY 2016 H1 20172 % change Total Revenue Core Operating Profit
EUR Product Sales 0.90 0.92 -2% +179 +123
JPY Product Sales 108.84 112.43 -3% +104 +71
CNY Product Sales 6.65 6.87 -3% +131 +74
SEK Costs 8.56 8.86 -3% +7 -98
GBP Costs 0.74 0.79 -7% +29 -131
Other3 +194 +124
1Based on 2016 results at 2016 actual exchange rates.2Based on average daily spot rates between 1 January and 30 June 2017.3Other important currencies include AUD, BRL, CAD, KRW and RUB.
Foreign-Exchange 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 30 June 2017,
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.
Related-Party Transactions
There have been no significant related-party transactions in the period.
Principal Risks and Uncertainties
It is not anticipated that the nature of the principal risks and uncertainties that affect the business, and which are set
out on pages 20 to 21 of the Annual Report and Form 20-F Information 2016, will change in respect of the second six months
of the financial year. Further information on our key risk management and assurance processes are set out on pages 214 to
225 of the Annual Report and Form 20-F Information 2016. In summary, the principal risks and uncertainties listed in the
Annual Report and 20-F Information 2016 are:
a) Medicine Pipeline and Intellectual Property Risks
Failure or delay in delivery of pipeline and new medicines; failure to meet quality, regulatory and ethical medicine
approval and disclosure requirements; failure to secure and protect product intellectual property.
b) Commercialisation Risks
Competitive pressures including externally driven demand, pricing and access; failures or delays in quality execution of
commercial strategies.
c) Supply Chain and Business-Execution Risks
Failure to maintain a supply of compliant, quality product; failure of information technology and data security and
privacy; delivery of gains from productivity initiatives; failure to attract, develop, engage and retain talented and
capable employees at all levels.
d) Legal, Regulatory and Compliance Risks
Safety and efficacy of marketed products is questioned; adverse outcome of defence of product, pricing and practices
litigation; failure to meet regulatory and ethical expectations on commercial practices, including bribery and corruption,
and scientific exchanges.
e) Economic and Financial Risks
Failure to achieve strategic plans and meet targets and expectations.
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) Agreement for Seloken In Europe
On 22 May 2017, AstraZeneca announced that it had entered into an agreement with Recordati for the commercial rights to
Seloken/Seloken ZOK (metoprolol tartrate and metoprolol succinate respectively) and associated Logimax fixed-dose
combination (metoprolol succinate and felodipine) treatments in Europe. Metoprolol succinate is a beta-blocker for the
control of hypertension, angina and heart failure. AstraZeneca will continue to commercialise the medicines in all other
markets, where it holds the rights.
Recordati paid AstraZeneca $291m upon completion of the agreement in June 2017 (completion pending in Romania). AstraZeneca
will also receive sales-related income through tiered royalties, initially at a double-digit percentage of sales.
AstraZeneca manufactures and supplies the medicines to Recordati under a supply agreement. Based on the level of ongoing
interest AstraZeneca will retain in the brands in Europe, the $291m upfront and tiered royalties are reported under Other
Operating Income and Expense in the Company's financial statements.
b) Agreement with Grünenthal to divest rights to migraine treatment Zomig
On 7 June 2017, AstraZeneca announced that it had entered an agreement with Grünenthal for the global rights to Zomig
(zolmitriptan) outside Japan. Zomig is indicated for the acute treatment of migraines and cluster headaches, an area of
medicine outside AstraZeneca's strategic focus.
Grünenthal paid AstraZeneca consideration of $200m in June 2017, of which $165m was reported within Other Operating Income
and Expense in the first half, with the remainder being deferred. AstraZeneca will also receive up to an additional $102m
in future milestone payments. Grünenthal acquired the rights to Zomig in all markets outside Japan, including the US, where
the rights were previously licensed to Impax Pharmaceuticals (Impax). Impax continues to market Zomig in the US.
AstraZeneca continues to manufacture and supply the medicine to Grünenthal during a transition period.
c) Collaboration to develop and commercialise anticalin-based inhaled treatments for Respiratory Diseases
On 3 May 2017, AstraZeneca announced a strategic collaboration in respiratory diseases with Pieris Pharmaceuticals, Inc.
(Pieris) to develop novel inhaled drugs that leverage Pieris's Anticalin platform. Anticalin molecules are engineered
proteins which can mimic antibodies by binding to sites either on other proteins or on small molecules. They are smaller
than monoclonal antibodies, offering the potential of direct delivery to the lung.
AstraZeneca will make upfront and near-term milestone payments to Pieris in the amount of $57.5m, anticipated in Q3 2017.
Pieris has the potential to receive development-dependent milestones and eventual commercial payments for all products not
exceeding $2.1bn, as well as tiered royalties on the sales of any potential products commercialised by AstraZeneca.
d) Senior Executive Team (SET) changes
On 28 April 2017, a number of changes to the SET took effect. Iskra Reic was appointed Executive Vice President (EVP),
Europe, with responsibility for sales, marketing and commercial operations across AstraZeneca's businesses in 30 European
countries. Jamie Freedman was appointed EVP & Head, Oncology Business Unit, with responsibility for sales, marketing, and
medical affairs and diagnostics activities for Oncology medicines globally, as well as Oncology commercial operations in
the US, UK, Spain, Italy, Germany and France. Both became members of the SET, reporting to the Chief Executive Officer. In
addition, having joined the SET in December 2016, the responsibilities of Leon Wang, EVP, International were expanded to
add Latin America & Brazil, Russia & Eurasia, and the Middle East & Africa to his previous Asia-Pacific territories. He
continues to report to the Chief Executive Officer.
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 27 April 2017 (the period):
Regulatory Approvals 4 - Imfinzi - bladder cancer (US)- Faslodex - breast cancer (1st line) (EU, JP)- Kyntheum (broadalumab) - psoriasis (EU) (received by partner)
Regulatory Submission Acceptances 2 - Lynparza - ovarian cancer (2nd line) (EU, JP)- Bevespi - COPD (EU)
Phase III or Major Data Readouts 3 - Imfinzi - lung cancer (PACIFIC)- Bydureon - type-2 diabetes CVOT (met primary safety objective, did not meet primary efficacy objective)- tralokinumab -
severe, uncontrolled asthma (did not meet primary endpoint)
New Molecular Entities 12 Oncology- Imfinzi + treme - multiple cancers- acalabrutinib - blood cancers- moxetumomab pasudotox - leukaemia- selumetinib - thyroid cancer-
(NMEs) In Phase III Trials Or Under Regulatory Review savolitinib - kidney cancer Cardiovascular & Metabolic Diseases- ZS-9 (sodium zirconium cyclosilicate)* - hyperkalaemia- roxadustat* - anaemia Respiratory-
benralizumab - severe, uncontrolled asthma*, COPD- tralokinumab - severe, uncontrolled asthma- PT010 - COPD Other- anifrolumab - lupus- lanabecestat -
Alzheimer's disease
Projects in Clinical Pipeline 129
*Under Regulatory Review
The table shown as of 27 July 2017
ONCOLOGY
AstraZeneca has a deep-rooted heritage in Oncology and offers a growing line of new medicines that has the potential to
transform patients' lives and the Company's future. At least six Oncology medicines are expected to be launched between
2014 and 2020, of which Lynparza, Tagrisso and Imfinzi are already benefitting patients. An extensive pipeline of
small-molecule and biologic medicines is in development and the Company is committed to advancing New Oncology, primarily
focused on lung, ovarian, breast and blood cancers, as one of AstraZeneca's five Growth Platforms.
At the recent 2017 American Society of Clinical Oncology (ASCO) annual meeting, AstraZeneca presented new data on its
expanding line of cancer medicines through 100 Company-sponsored and supported abstracts, including five 'Best of ASCO'
presentations, 11 oral presentations and eight poster discussions. Content highlighted new data on approved and potential
new medicines from the Company's pipeline across multiple scientific platforms and tumour types.
a) Lynparza (multiple cancers)
During the period, the Company received regulatory submission acceptance in the EU for Lynparza's SOLO-2 trial in women
with germline BRCA-mutated, platinum-sensitive relapsed ovarian cancer. Among other objectives, this regulatory submission
aimed at bringing the new Lynparza tablets to patients in the EU. Furthermore, the Company made a regulatory submission in
Japan for the use of Lynparza in 2nd-line, BRCA-mutated advanced or metastatic ovarian cancer. This followed an Orphan Drug
Designation received during the first quarter of 2017. Presently, there are no approved medicines in Japan to treat
BRCA-mutated ovarian cancer.
At the 2017 ASCO annual meeting, the Company presented positive results from the Phase III OlympiAD trial of patients with
HER2-negative, metastatic breast cancer, harbouring germline BRCA1 or BRCA2 mutations. Results showed a
statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) for patients treated
with Lynparza tablets (300mg twice daily), compared to treatment with physician's choice of standard-of-care (SoC)
chemotherapy. The trial met its primary endpoint, showing that patients treated with Lynparza had a 42% reduction in the
risk of disease worsening or death (hazard ratio, HR=0.58; 95% CI 0.43-0.80) and a median PFS of 7.0 vs 4.2 months compared
to those who received chemotherapy (capecitabine, vinorelbine, eribulin). The primary endpoint was assessed by blinded
independent central review (BICR). The OlympiAD trial was the first positive outcome in a Phase III trial to evaluate the
safety and efficacy of a PARP inhibitor beyond ovarian cancer.
b) Tagrisso (lung cancer)
While the original results of the AURA3 trial were presented in 2016, a follow-on analysis at the 2017 ASCO meeting showed
that Tagrisso also demonstrated efficacy in those patients with disease progression to the central nervous system (CNS).
The data were consistent with earlier clinical and pre-clinical findings showing the potential of Tagrisso to penetrate the
blood-brain barrier. In the newly-shared results of AURA3, Tagrisso 80mg once-daily tablets demonstrated that, in patients
with CNS metastases, there was no significant imbalance in the hazard ratio (HR=0.32 or 68% reduction in the risk of
disease worsening or death) compared to patients in AURA3 overall (HR=0.30). In the AURA3 trial, the adverse-event profiles
for Tagrisso and platinum-based doublet chemotherapy were consistent with previous trials.
c) Faslodex (breast cancer)
On 26 July 2017, the Company announced approval in the EU for the expansion of Faslodex use into 1st-line treatment of
hormone-receptor positive, metastatic breast cancer. The approval was based on data from the Phase III FALCON trial, where
Faslodex 500mg demonstrated superiority over anastrozole 1mg in the treatment of locally-advanced or metastatic breast
cancer in post-menopausal patients who had not received prior hormonal-based medicine for HR+ breast cancer. The FALCON
trial data showed that Faslodex significantly reduced the risk of disease worsening or death by 20% (HR=0.80). This new
indication for Faslodex was approved in Japan and Russia during the period and is under review in the US.
d) Savolitinib (kidney cancer)
AstraZeneca, and its partner Hutchison China MediTech Limited, announced in June 2017 that they had initiated a global,
pivotal Phase III, open-label, randomised multi-centre registrational trial of the highly-selective inhibitor of c-MET
receptor tyrosine kinase, savolitinib, in c-MET-driven papillary renal cell carcinoma (PRCC). This is the first pivotal
trial ever conducted in c-MET-driven PRCC and the first molecularly-selected trial in renal cell carcinoma (RCC), a form of
kidney cancer. The SAVOIR trial is designed to support registration of this potential medicine in the US and EU and is
supported by the results of the Phase II trial.
e) Imfinzi (multiple cancers)
The Company continues to advance multiple monotherapy trials of Imfinzi and combination trials of Imfinzi with tremelimumab
and other potential new medicines. The combination of Imfinzi and tremelimumab is being assessed in Phase III trials in
bladder cancer, non-small cell lung cancer NSCLC, small cell lung cancer (SCLC), head and neck squamous cell carcinoma
(HNSCC) and in Phase I/II trials in hepatocellular carcinoma, gastric cancer, pancreatic cancer and haematological
malignancies.
BladderCancer
On 1 May 2017, Imfinzi received accelerated approval in the US for the treatment of patients with locally-advanced or mUC
who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within
12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery. Approval was
granted in an 'all-comer' population based on both tumour response rate and duration of response. Data from Study 1108,
which supported this approval, was shared at the recent 2017 ASCO annual meeting and showed a 17.0% objective response rate
(ORR) by BICR in all-comers and a 26.3% ORR in patients with PDL1-positive tumours.
The STRONG trial, a Phase IIIb, modular, five-year safety, open-label trial commenced dosing in the period and will
evaluate the safety of the fixed dosing of Imfinzi + tremelimumab combination therapy or Imfinzi monotherapy in patients
with advanced solid tumours (via tumour specific modules). The first tumour module dosed was bladder cancer.
Ongoing key trials include:
DANUBE III 1st line Cisplatin chemo-therapy- eligible/ineligible bladder cancer Imfinzi, Imfinzi + treme vs SoC chemotherapy FPCD1 Q4 2015 LPCD2 Q1 20173 First data anticipated H2 2018 Recruitment completed
DANUBE
III
1st line
Cisplatin chemo-therapy- eligible/ineligible bladder cancer
Imfinzi, Imfinzi + treme vs SoC chemotherapy
FPCD1 Q4 2015 LPCD2 Q1 20173 First data anticipated H2 2018
Recruitment completed
1First Patient Commenced Dosing
2Last Patient Commenced Dosing
3Global trial, excluding China
Lung Cancer
During the period, the Company maintained strong momentum in its immunotherapy efforts in lung cancer, with an early data
readout from the PACIFIC trial. This is a Phase III, randomised, double-blinded, placebo-controlled multi-centre trial of
Imfinzi
as sequential treatment in patients with locally-advanced, unresectable (Stage III) NSCLC, who had not progressed following
standard platinum-based chemotherapy concurrent with radiation therapy. A planned interim analysis focused on PFS,
conducted by an Independent Data Monitoring Committee, concluded that the trial had already met a primary endpoint by
showing statistically-significant and clinically-meaningful reduction in the risk of disease worsening or death (PFS), as
assessed by a blinded and independent review panel, in patients receiving
Imfinzi
compared to placebo. The results also demonstrated a favourable benefit/risk profile. The trial will continue in order to
evaluate overall survival (OS), the other primary endpoint, which will be assessed in due course as specified by the
protocol. AstraZeneca plans to submit the initial results from the PACIFIC trial for presentation at a forthcoming medical
meeting.
Additional progress was made in the treatment of lung cancer when the last patient commenced dosing in the NEPTUNE trial,
as well as first patient commencing dosing in the POSEIDON trial. Ongoing key trials are included in the following table:
Monotherapy
ADJUVANT* III N/A Stage Ib-IIIa NSCLC Imfinzi vs placebo FPCD Q1 2015 First data anticipated 2020 Recruitment ongoing
PACIFIC III N/A Stage III unresectable NSCLC Imfinzi vs placebo FPCD Q2 2014 LPCD Q2 2016 Final OS data anticipated 2019 Recruitment completed PFS data positive Q2 2017
PEARL III 1st line NSCLC (Asia) Imfinzi vs SoC chemotherapy FPCD Q1 2017 First data anticipated 2020 Recruitment ongoing
Combination therapy
MYSTIC III 1st line NSCLC Imfinzi, Imfinzi + treme vs SoC chemotherapy FPCD Q3 2015 LPCD Q3 2016 First data anticipated mid-2017 Recruitment completed
NEPTUNE III 1st line NSCLC Imfinzi + treme vs SoC chemotherapy FPCD Q4 2015 LPCD Q2 2017 First data anticipated H2 2018 Recruitment completed
POSEIDON III 1st line NSCLC Imfinzi + SoC, Imfinzi + treme + SoC vs SoC chemotherapy FPCD Q2 2017 First data anticipated 2019 Recruitment ongoing
ARCTIC III 3rd line PDL1- low/neg. NSCLC Imfinzi, tremelimumab, Imfinzi + treme vs SoC chemotherapy FPCD Q2 2015 LPCD Q3 2016 First data anticipated H2 2017 Recruitment completed
CASPIAN III 1st line Small-cell lung cancer (SCLC) Imfinzi + SoC, Imfinzi + treme + SoC vs SoC chemotherapy FPCD Q1 2017 First data anticipated 2020 Recruitment ongoing
CASPIAN
III
1st line
Small-cell lung cancer (SCLC)
Imfinzi + SoC, Imfinzi + treme + SoC vs SoC chemotherapy
FPCD Q1 2017 First data anticipated 2020
Recruitment ongoing
*Conducted by the National Cancer Institute of Canada
Head and Neck Cancer
During the period, there was no update from the ongoing programme. Ongoing key trials include: Name Phase Line of Treatment Population Design Timelines Status Combination therapy KESTREL III 1st line HNSCC Imfinzi, Imfinzi + treme vs SoC FPCD Q4 2015 LPCD Q1 2017 First data anticipated H1 2018 Recruitment completed EAGLE III 2nd line HNSCC Imfinzi, Imfinzi + treme vs SoC FPCD Q4 2015 First data anticipated H1 2018 Recruitment ongoing
Combination therapy
KESTREL III 1st line HNSCC Imfinzi, Imfinzi + treme vs SoC FPCD Q4 2015 LPCD Q1 2017 First data anticipated H1 2018 Recruitment completed
EAGLE III 2nd line HNSCC Imfinzi, Imfinzi + treme vs SoC FPCD Q4 2015 First data anticipated H1 2018 Recruitment ongoing
FPCD Q4 2015 First data anticipated H1 2018
Recruitment ongoing
CARDIOVASCULAR & METABOLIC DISEASES
AstraZeneca has been a driving force in cardiovascular (CV) science for more than 100 years and continues to be a pioneer
in the industry, both with its current portfolio and innovation-rich pipeline. This therapy area includes a broad diabetes
portfolio, differentiated devices and unique small and large-molecule programmes to reduce morbidity, mortality and organ
damage across CV, renal and metabolic diseases.
a) Brilique (CV disease)
During the period, a new formulation of
Brilique
90mg, an
orally-dispersable tablet (
ODT),
was approved by the EMA, making Brilique the first and only P2Y12 receptor inhibitor to be made available in ODT form in
Europe. This approval will expand the use of Brilique in patients who are unable to swallow traditional tablets of the
medicine.
b
) Farxiga
(
type
-2
diabetes
)
At the 2017 American Diabetes Association (ADA) Scientific Sessions, AstraZeneca presented over 50 abstracts, including
updated safety data on the risk-benefit profile of Farxiga and data from the DURATION-8 trial evaluating the efficacy and
safety of Farxiga in combination with Bydureon.
In the updated safety analysis of Farxiga, data pooled from 30 Phase IIb/III clinical trials showed no new safety signals
and the incidence of adverse events was generally similar to that in the control groups. Importantly, there was no
imbalance in lower-limb amputations, with eight (0.1%) patients and seven (0.2%) patients identified in the Farxiga and
control groups, respectively.
c) Bydureon (type-2diabetes)
Data from the DURATION-7 trial were presented in the period at the 2017 ADA meeting. The trial assessed the efficacy and
safety of adding Bydureon or placebo to insulin, in patients whose type-2 diabetes was inadequately controlled with basal
insulin and metformin. The trial showed that a once-weekly injection of Bydureon is an effective and well-tolerated option
for patients with type-2 diabetes and shows benefits, such as 25.1% of patients achieving target A1C levels, lower fasting
glucose levels, reduced body weight (1.5kg) and better glycaemic control than patients on placebo. During the period,
regulatory submissions for adding these results to the existing Bydureon label were accepted in the US and the EU.
The results from the Phase III EXSCEL cardiovascular outcomes trials are covered below.
d) Medicines in CV outcomes trials
As a follow-up to the CVD-REAL real-world evidence study presented at the 2017 American College of Cardiology Session and
Expo, AstraZeneca shared additional findings at the 2017 European Society of Cardiology Heart Failure meeting and at the
2017 ADA meeting from the main data set of over 300,000 patients. The findings showed that patients with and without
established CV disease were at a lower risk of both death and heart failure after initiation of treatment with SGLT2
medicines versus other oral anti-diabetic (OAD) medicines. The lower risk of events with SGLT2 medicines versus other OAD
medicines was consistent across sub-groups and geographies, suggesting that SGLT2 medicines may benefit a broad population
of patients.
In analyses specific to Farxiga, compared to DPP-4 medicines in a two-country data set of approximately 34,000 patients,
data showed that Farxiga was associated with lower risk of hypertensive heart failure (HF) (37%) and death (27%), as well
as a Major Adverse Cardiac Events (MACE), a composite endpoint of CV death, non-fatal myocardial infarction or non-fatal
stroke (29%), and hospitalisation for kidney disease (62%). In this Farxiga-specific data set, the majority of patients
(79%) did not have established CV disease at the time their medical records were first evaluated.
During the period, the Company announced that the EXSCEL trial had met its primary safety objective of non-inferiority for
MACE, in adults with type-2 diabetes at a wide range of CV risk. These results addressed the US FDA requirement that
medicines to treat type-2 diabetes are not associated with an increase in CV risk. Fewer CV events were observed in the
Bydureon arm of the trial; however, the efficacy objective of a superior reduction in MACE did not reach statistical
significance. Data were consistent with the known safety profile of Bydureon and will be presented at the September 2017
European Association for the Study of Diabetes meeting in Lisbon, Portugal.
Ongoing outcomes trials for patients with type-2 diabetes or dyslipidaemia (abnormal levels of lipids and lipoproteins in
the blood) are highlighted in the following table:
Bydureon EXSCEL GLP-1 agonist ~14,000 patients with type-2 diabetes Time to first occurrence of CV death, non-fatal myocardial infarction or non-fatal stroke Data presentation: EASD1, September 2017
Farxiga DECLARE SGLT2 inhibitor ~17,0002 patients with type-2 diabetes Time to first occurrence of CV death, non-fatal myocardial infarction or non-fatal stroke H2 2018 (final analysis)
Farxiga DAPA-HF SGLT2 inhibitor ~4,500 patients with heart failure Time to first occurrence of CV death or hospitalisation for HF or an urgent HF visit FPCD Q1 2017
Farxiga DAPA-CKD SGLT2 inhibitor ~4,000 patients with chronic kidney disease (CKD) Time to first occurrence of ≥50% sustained decline in eGFR3 or reaching ESRD4 or CV death or renal death FPCD Q1 2017
Epanova STRENGTH Omega-3 carboxylic acids ~13,000 patients with mixed dyslipidaemia Time to first occurrence of CV death, non-fatal myocardial infarction or non-fatal stroke 2019 (final analysis)
Epanova
STRENGTH
Omega-3 carboxylic acids
~13,000 patients with mixed dyslipidaemia
Time to first occurrence of CV death, non-fatal myocardial infarction or non-fatal stroke
2019 (final analysis)
1European Association for the Study of Diabetes
2Includes ~10,000 patients who have had no prior index event (primary prevention) and ~7,000 patients who have suffered an
index event (secondary prevention)
3Estimated Glomerular Filtration Rate
4End Stage Renal Disease
e) ZS-9 (sodium zirconium cyclosilicate) (hyperkalaemia)
In April 2017, the EMA informed AstraZeneca that the Marketing Authorisation Application decision process for ZS-9 was put
on hold until the agency had performed an inspection of the dedicated substance-manufacturing facility in Texas. This
followed receipt of a second Complete Response Letter from the US FDA, as announced on 17 March 2017. During the period,
the Company made progress in addressing the manufacturing deficiencies identified by the FDA inspection and expects to
provide an update in due course.
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 anticipated launches between 2017 and 2020. The capability in inhalation
technology spans both pressurised metered-dose inhalers 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) Benralizumab (asthma)
During the American Thoracic Society international conference in May 2017, the Company presented data for the Phase III
ZONDA trial, showing a statistically-significant and clinically-meaningful reduction in daily-maintenance, oral
corticosteroid (OCS) use compared with placebo for patients with severe, uncontrolled OCS-dependent eosinophilic asthma
receiving benralizumab. Patients treated with benralizumab achieved a median reduction in OCS dose of 75% and were more
than four times as likely to reduce their OCS dose than those on placebo. Benralizumab also reduced overall exacerbation
rates by 70% and exacerbations requiring emergency-department visits or hospitalisations by 93%. These positive trial
results were published simultaneously in the New England Journal of Medicine.
b) Tralokinumab (asthma)
During the period, the STRATOS 1 trial of tralokinumab, an anti-interleukin-13 (IL-13) human monoclonal antibody, did not
meet its primary endpoint of a significant reduction in the annual asthma exacerbation rate (AAER) in the overall
population of severe, uncontrolled-asthma patients, compared with placebo. However, a clinically-relevant reduction in AAER
was observed in a sub-population of patients with an elevated biomarker associated with increased IL-13 activity. This
sub-group of patients will now be the focus for the future analysis of STRATOS 2, the second ongoing pivotal Phase III
trial, which is anticipated to report later this year. Potential future regulatory submissions for tralokinumab will be
dependent on the combined analysis of both STRATOS 1 and STRATOS 2.
c) PT010 (COPD)
PT010 is currently in Phase III trials in patients with moderate to severe COPD. During the period, the last patient
commenced dosing in both the KRONOS and TELOS trials. Data for PT010 is anticipated in the first half of 2018.
OTHER
a) Brodalumab (psoriasis)
On 20 July 2017, AstraZeneca announced that its partner, LEO Pharma, was granted full approval by the EMA for Kyntheum
(brodalumab) for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic
therapy or phototherapy and have failed to respond or no longer respond to other systemic therapies. Through a
collaboration agreement, LEO Pharma holds exclusive rights to develop and commercialise Kyntheum in Europe.
In the US, brodalumab is approved under the brand name Siliq and marketed by AstraZeneca's partner, Valeant.
b) Anifrolumab (lupus)
During the period, the Company completed the enrolment of the first of two Phase III trials (TULIP 1) of anifrolumab in
patients with moderate-to-severe systemic lupus erythematosus (SLE, or lupus). Data readouts from both the TULIP 1 and
TULIP 2 trials are expected in H2 2018, with anticipated regulatory submissions in 2019.
The Company also enrolled the first patient into the SLE Prospective Observational Cohort Study (SPOCS) trial, a unique,
AstraZeneca-led collaboration between industry and academic centres to characterise SLE disease activity, treatment,
patient reported outcomes, comorbidities, healthcare resource use and the impact on quality of life among the general
population of patients with moderate to severe SLE and by the type-I Interferon gene signature (IFNGS) test high-versus-low
patient groups. SPOCS will enrol c.1,500 patients and provide important information about possible associations of type-I
IFNGS with disease characteristics and outcomes for patients with moderate-to-severe SLE.
AstraZeneca Development Pipeline 30 June 2017
________________________________________________________________________________________
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
acalabrutinib# BTK inhibitor B-cell malignancy Q1 2015 H2 2017(Orphan drug)
acalabrutinib# BTK inhibitor 1st-line chronic lymphocytic leukaemia Q3 2015 2020(Orphan drug) 2020(Orphan drug)
acalabrutinib# BTK inhibitor relapsed/refractory chronic lymphocytic leukaemia, high risk Q4 2015 2020(Orphan drug) 2020(Orphan drug)
acalabrutinib BTK inhibitor 1st-line mantle cell lymphoma Q1 2017 2023
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
Imfinzi# (durvalumab#) +tremelimumab PD-L1 mAb + CTLA-4 mAb 3rd-line non-small cell lung cancer Q2 2015 H2 2017 H2 2017 H2 2017
ARCTIC
Imfinzi# (durvalumab#) + tremelimumabMYSTIC PD-L1 mAb + CTLA-4 mAb 1st-line non-small cell lung cancer Q3 2015 H2 2017 H2 2017 H2 2017
Imfinzi# (durvalumab#) + tremelimumabNEPTUNE PD-L1 mAb + CTLA-4 mAb 1st-line non-small cell lung cancer Q4 2015 2019 2019 2019 2020
Imfinzi# (durvalumab#) + tremelimumab + chemotherapyPOSEIDON PD-L1 mAb + CTLA-4 mAb 1st-line non-small cell lung cancer Q2 2017 2019 2019 2019 2020
Imfinzi# (durvalumab#) + tremelimumab + SoCCASPIAN PD-L1 mAb + CTLA-4 mAb + SoC 1st-line small cell lung cancer Q1 2017 2019 2019 2019
Imfinzi# (durvalumab#) + tremelimumab PD-L1 mAb + CTLA-4 mAb 1st-line head and neck squamous cell carcinoma Q4 2015 H2 2018 H2 2018 H2 2018
KESTREL
Imfinzi# (durvalumab#) + tremelimumab PD-L1 mAb + CTLA-4 mAb 2nd-line head and neck squamous cell carcinoma Q4 2015 H2 2018 H2 2018 H2 2018
EAGLE
Imfinzi# (durvalumab#) + tremelimumabDANUBE PD-L1 mAb + CTLA-4 mAb 1st-line bladder cancer Q4 2015 H2 2018 H2 2018 H2 2018
Lynparza¶ + cediranibCONCERTO PARP inhibitor + VEGF inhibitor recurrent platinum-resistant ovarian cancer Q1 2017 2019
Cardiovascular & Metabolic Diseases
Epanova omega-3 carboxylic acids severe hypertriglyceridemia Approved 2018
ZS-9 (sodium zirconium cyclosilicate) potassium binder hyperkalaemia - Accepted1 2019
roxadustat# OLYMPUS (US) ROCKIES (US) hypoxia-inducible factor prolyl hydroxylase inhibitor anaemia in chronic kidney disease/end stage renal disease Q3 2014 2018 Initiated2
Respiratory
Bevespi Aerosphere (PT003) LABA/LAMA chronic obstructive pulmonary disease Launched Accepted 2018 2018
benralizumab#CALIMA SIROCCO ZONDABISEBORAGREGALE IL-5R mAb severe asthma Accepted Accepted Accepted 2021
benralizumab#TERRANOVA GALATHEA IL-5R mAb chronic obstructive pulmonary disease Q3 2014 H2 2018 H2 2018 2019
PT010 LABA/LAMA/ ICS chronic obstructive pulmonary disease Q3 2015 2019 2019 H2 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
lanabecestat#AMARANTH + extension, DAYBREAK-ALZ beta-secretase inhibitor alzheimer's disease Q2 2016 2020(Fast Track) 2020 2020
alzheimer's disease
Q2 2016
2020(Fast Track)
2020
2020
¶ Registrational Phase IItrial
# Collaboration
1 CHMP positive opinion received
2 Rolling New Drug Application (NDA) regulatory submission initiated in Q4 2016
Phases I and II
NMEs and significant additional indications
Oncology
Imfinzi#(durvalumab#) PD-L1 mAb solid tumours II Q3 2014
Imfinzi# (durvalumab#) + tremelimumab PD-L1 mAb + CTLA-4 mAb hepatocellular carcinoma (liver cancer) II Q4 2016
Imfinzi# (durvalumab#) + tremelimumab PD-L1 mAb + CTLA-4 mAb gastric cancer II Q2 2015
Imfinzi# (durvalumab#) + AZD5069 PD-L1 mAb + CXCR2 antagonist pancreatic ductal adenocarcinoma II Q2 2017
Imfinzi# (durvalumab#) + AZD5069 or Imfinzi#(durvalumab#) + AZD9150# PD-L1 mAb + CXCR2 antagonist or PD-L1 mAb + STAT3 inhibitor head and neck squamous cell carcinoma II Q3 2015
Imfinzi# (durvalumab#) + dabrafenib + trametinib PD-L1 mAb+ BRAF inhibitor + MEK inhibitor melanoma I Q1 2014
Imfinzi# (durvalumab#) + AZD1775# PD-L1 mAb + Wee1 inhibitor solid tumours I Q4 2015
Imfinzi# (durvalumab#) + MEDI0680 PD-L1 mAb + PD-1 mAb solid tumours II Q3 2016
Imfinzi# (durvalumab#) or Imfinzi# (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
Imfinzi# (durvalumab#) + Iressa PD-L1 mAb+ EGFR inhibitor non-small cell lung cancer I Q2 2014
Imfinzi# (durvalumab#) + MEDI0562# PD-L1 mAb + humanised OX40 agonist solid tumours I Q2 2016
Imfinzi# (durvalumab#) + MEDI9197# PD-L1 mAb + TLR 7/8 agonist solid tumours I Q2 2017
Imfinzi# (durvalumab#) + MEDI9447 PD-L1 mAb + CD73 mAb solid tumours I Q1 2016
Imfinzi# (durvalumab#) + monalizumab PD-L1 mAb + NKG2a mAb solid tumours I Q1 2016
Imfinzi# (durvalumab#) + selumetinib PD-L1 mAb + MEK inhibitor solid tumours I Q4 2015
Imfinzi# (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 non-small cell lung cancer II Q2 2016
Tagrisso BLOOM EGFR inhibitor CNS metastases in advanced EGFRm non-small cell lung cancer II Q4 2015
AZD1775#+ chemotherapy Wee1 inhibitor + chemotherapy ovarian cancer II Q4 2012
AZD1775# Wee1 inhibitor solid tumours II Q1 2016
vistusertib 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
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