AstraZeneca and Incyte in Collaboration

AstraZeneca and Incyte Corporation announced a new collaboration to evaluate the efficacy and safety of Incyte’s Janus-associated kinase (JAK) 1 inhibitor, INCB39110, in combination with AstraZeneca’s next generation epidermal growth factor receptor (EGFR) inhibitor, Tagrisso^® (osimertinib). The combination will be assessed as a second line treatment for patients with EGFR mutation-positive non-small cell lung cancer (NSCLC), who have been treated with a first generation EGFR tyrosine kinase inhibitor (TKI) and subsequently developed the T790M resistance mutation.

There is increasing evidence that signalling through the JAK-STAT (signal transducer and activator of transcription) pathway could be a contributing factor in resistance to EGFR TKI treatment in patients with EGFR mutation NSCLC. Blocking both JAK and EGFR activity may therefore offer an improved targeted treatment benefit in some patients.

Under the terms of the agreement, AstraZeneca and Incyte will collaborate on a Phase I/II study, to be conducted by Incyte. The Phase I part of the trial is expected to establish a recommended dose regimen for the combination of INCB39110 and Tagrisso, while the Phase II part of the study will assess the safety and efficacy profile. Results from the study will be used to determine whether further clinical development of this combination is warranted.

ZURAMPIC approved by US FDA for patients with gout

AstraZeneca announced that the US Food and Drug Administration (FDA) has approved ZURAMPIC® (lesinurad) 200mg tablets in combination with a xanthine oxidase inhibitor (XOI) for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid (sUA) levels with an XOI alone.

ZURAMPIC inhibits the urate transporter, URAT1, which is responsible for the majority of the renal reabsorption of uric acid. By inhibiting URAT1, ZURAMPIC increases uric acid excretion and thereby lowers sUA.

In combination with the current standard of care, XOIs allopurinol or febuxostat, ZURAMPIC provides a dual mechanism of action to increase excretion and decrease production of uric acid, enabling more patients with inadequately controlled gout to achieve target treatment goals.

The FDA approval is based on data from three pivotal Phase III studies, CLEAR1, CLEAR2 and CRYSTAL, which represent the largest clinical trial data set of gout patients (n=1,537 total) treated with combination urate lowering therapy.

Gout is a serious and debilitating form of inflammatory arthritis caused by hyperuricemia (elevated sUA). It affects millions of people around the globe, many of whom do not reach recommended sUA treatment goals on XOIs, which decrease production of uric acid. For those inadequately controlled patients, the addition of a urate-lowering therapy to increase excretion of uric acid may help them achieve treatment goals.

Takeda Agree Sale of Respiratory Portfolio to AstraZeneca

Takeda Pharmaceutical Company Limited announced that it has entered into a definitive agreement to sell its respiratory portfolio to AstraZeneca. In 2014 Takeda defined four therapeutic areas of focus: Gastroenterology, Oncology, Central Nervous System, and Cardiovascular and Metabolic. This divestiture will allow Takeda to work on becoming best-in-class in these therapeutic areas, while maintaining continuity of care for patients.

Under the terms of the agreement, AstraZeneca will acquire the respiratory business including products Daxas (roflumilast), Alvesco and Omnaris (ciclesonide). The acquisition will also include regional and local products, as well as several pre-clinical assets. A number of Takeda employees will transfer to AstraZeneca upon completion of the divestiture.

The financial impact from this divestiture on Takeda’s 2015 consolidated financial statements is expected to be minimal. Sales of respiratory products, Daxas, Alvesco and Omnaris, totaled approximately 24 billion yen in fiscal year 2014. The transaction is expected to close during the first calendar quarter of 2016, subject to customary closing conditions.

AstraZeneca continues strategic investment in China

AstraZeneca, along with MedImmune, its global biologics research and development arm, announced a range of strategic initiatives to accelerate the delivery of innovative biologics and targeted medicines to patients in China, the company’s second largest market globally and a key growth platform. The initiatives and investments include:

• A strategic alliance with WuXi AppTec, a leading Chinese biologics manufacturer and contract research organisation, to produce innovative biologics locally in China. Under the agreement, AstraZeneca has the option to acquire WuXi AppTec’s biologics manufacturing capacity in Wuxi City in the next few years through an overall investment approximating $100 million. Prior to that, Wuxi AppTec remains the company’s exclusive partner for R&D manufacturing for innovative biologics in China.
  This strategic alliance will bring cutting-edge research and technical capability for biologics to China with the aim of addressing unmet patient needs in AstraZeneca’s main therapy areas of respiratory, inflammation and autoimmunity; cardiovascular and metabolic diseases, and oncology. The alliance builds on the existing joint venture between MedImmune and WuXi AppTec to develop and commercialise MEDI5117, a novel biologic for autoimmune and inflammatory diseases, in China.

• An investment of $50 million to build an additional development and launch facility alongside our existing manufacturing site in Wuxi City to support the development and manufacture of innovative small molecules discovered in China and our global R&D sites.
  
• Additional investments include the creation of a new global hub for Pharmaceutical Development – alongside those in the UK and Sweden - with up to 50 scientists based in Shanghai and Wuxi City, to support both China and global needs. AstraZeneca is also establishing an integrated China medicines development organisation, bringing together early and late-stage medicines development across small molecules and biologics.

Celgene in Collaboration with Astrazeneca

Celgene Corporation and AstraZeneca announced the initiation of the FUSION clinical development program of durvalumab (MEDI4736), an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1) in hematologic disorders.

The FUSION program is part of a strategic collaboration with AstraZeneca and its global biologics research and development arm MedImmune, to develop and commercialize durvalumab across a range of blood cancers including non-Hodgkin's lymphoma, myelodysplastic syndromes and multiple myeloma.

The Celgene partnership with AstraZeneca/MedImmune is part of a comprehensive commitment to immuno-oncology that includes not only clinical-stage checkpoint inhibitors and t-cell activators, but also earlier stage research efforts on the tumor microenvironment focused on tumor-associated macrophages, monocytes, natural killer cells and regulatory T cells.

Durvalumab is an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1). Signals from PD-L1 help tumours avoid detection by the immune system. Durvalumab blocks these signals, countering the tumour's immune-evading tactics. Durvalumab is being investigated in an extensive clinical trial programme, as monotherapy or in combination in multiple cancer types. Durvalumab is an investigational product and has not been approved for any use.

AstraZeneca Plans Mobile App for Ovarian Cancer Studies

AstraZeneca announced plans to test a digital support service for women undergoing treatment for recurrent platinum-sensitive high-grade ovarian cancer in clinical trials of cediranib plus olaparib. Voluntis has developed the service in close clinical collaboration with AstraZeneca and the US National Cancer Institute (NCI). It is delivered through a smartphone app paired with a web portal to help clinicians and patients manage side effects of hypertension and diarrhoea sometimes associated with combination therapy with cediranib and olaparib. Such side effects are traditionally described to care teams through manual, time-consuming and non-digitised channels.

The app will be tested as a companion device in three separate clinical trials sponsored by the NCI beginning in the first quarter of 2016, under a Cooperative Research and Development Agreement between the NCI and AstraZeneca. This approach illustrates a clear focus on understanding the patient journey when developing therapeutic solutions. The service will also serve as a pilot within AstraZeneca’s broader strategy of using digital technology to complement treatment and to improve patient outcomes.

Cediranib is a highly potent, selective, orally-administered inhibitor of VEGF-1, -2 and -3 receptors. It has been shown to inhibit angiogenesis and lymphangiogenesis in the vascularization of platinum sensitive tumor types. In July 2015, cediranib filing was accepted by the European Medicines agency and awarded Orphan Drug status for the treatment of platinum sensitive relapse ovarian cancer. Cediranib also in development, in combination with Lynparza (olaparib), for platinum sensitive relapse ovarian cancer and platinum resistant relapse ovarian cancer.

Olaparib is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that exploits tumour DNA repair pathway deficiencies to preferentially kill cancer cells. This mode of action gives olaparib the potential for activity in a range of tumour types with DNA repair deficiencies. Olaparib is the first PARP inhibitor to be approved for patients with germline BRCA-mutated advanced ovarian cancer, and has been launched in the U.S. and Europe, with ongoing regulatory submissions across multiple markets. In addition to ovarian cancer, AstraZeneca is investigating the full potential of olaparib in multiple tumour types, with Phase III studies in second line gastric cancer, BRCA-mutated pancreatic cancer and adjuvant and metastatic BRCA-mutated breast cancers underway.

AstraZeneca enters into agreement with Perrigo

AstraZeneca announced that it has entered into an agreement with Perrigo Company plc for the divestment of US rights to Entocort® (budesonide), a gastroenterology medicine for patients with mild to moderate Crohn’s disease, an area of medicine outside AstraZeneca’s strategic focus.

Under the terms of the agreement, Perrigo will pay AstraZeneca $380 million upon completion of the transaction to acquire the rights to sell Entocort capsules and the authorised generic Entocort capsules marketed by Par Pharmaceuticals. The transaction does not include the transfer of any AstraZeneca employees or facilities.

US product sales of Entocort were $89 million in the year-to-date (at nine months 2015). The transaction is expected to complete by the end of 2015, subject to customary closing conditions. AstraZeneca’s 2015 Core Earnings Per Share guidance was upgraded at Year-To-Date & Third Quarter 2015 Results on 5 November and is maintained as it was provided, in the range of mid to high single-digit percentage increase versus the prior year and at constant exchange rates. As AstraZeneca will no longer retain an interest in the US rights to Entocort, the upfront gross receipt will be reported in Other Operating Income in the Company’s financial statements.

TAGRISSO approved by the US FDA

AstraZeneca announced that the US Food and Drug Administration (FDA) has approved TAGRISSO™ (AZD9291) 80mg once-daily tablets for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy.

AZD9291 is the only approved medicine indicated for patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer. This indication is approved under the FDA’s accelerated approval process based on tumour response rate and duration of response (DoR).

AZD9291 is an EGFR-TKI, a targeted cancer therapy, designed to inhibit both the activating, sensitising mutations (EGFRm), and T790M, a genetic mutation responsible for EGFR-TKI treatment resistance. Nearly two-thirds of NSCLC patients who are EGFR mutation-positive and experience disease progression after being treated with an EGFR-TKI develop the T790M resistance mutation, for which there have been limited treatment options.

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths, more than breast, prostate and colorectal cancers combined. Lung cancer has a five-year survival rate that is less than 20%. Approximately 85% of all lung cancers in the US are NSCLC; 10% to 15% of these are EGFR mutation-positive. Approximately two-thirds of patients treated with EGFR TKI therapy will acquire resistance related to the T790M mutation

FDA Advisory Committee recommends the approval of lesinurad for gout patients

AstraZeneca today announced that the US Food and Drug Administration’s (FDA) Arthritis Advisory Committee (AAC) voted 10 to 4 to recommend the approval of lesinurad 200mg tablets for the treatment of hyperuricemia associated with gout, in combination with a xanthine oxidase inhibitor (XOI). The AAC reviewed safety and efficacy data from the pivotal Phase III combination therapy programme trials, representing the largest clinical trial data set of gout patients treated with combination urate lowering therapy.

The FDA is not bound by the Advisory Committee’s recommendation but takes its advice into consideration when reviewing the application for a potential medicine. The Prescription Drug User Fee Act (PDUFA) target goal date for lesinurad is 29 December 2015.

If approved, lesinurad will be the first selective uric acid reabsorption inhibitor, or SURI, in the US. It inhibits the urate transporter, URAT1, which is responsible for the majority of the renal reabsorption of uric acid.

Sean Bohen, Executive Vice President of Global Medicines Development and Chief Medical Officer, AstraZeneca, said: “The Committee’s positive recommendation for lesinurad is an encouraging step for patients suffering from the debilitating effects of gout. We look forward to the outcome of the FDA’s review and the opportunity to provide a new treatment option that, when combined with a xanthine oxidase inhibitor, addresses both the under-excretion and over-production of uric acid, the underlying causes of gout.”

Gout is a serious and debilitating form of inflammatory arthritis caused by hyperuricemia (elevated serum uric acid (sUA)). Gout affects millions of Americans, many of whom do not reach recommended sUA treatment goals on the current standard of care (XOIs), which decrease production of uric acid. For those inadequately controlled patients, the addition of a urate lowering therapy to increase excretion of uric acid, may help them achieve treatment goals.

AstraZeneca purchases US biologics manufacturing facility

AstraZeneca added to its biologics manufacturing capability in the US with the purchase of a high-tech biologics bulk manufacturing facility from Amgen Inc. Over time, the LakeCentre facility, located in Boulder, Colorado will increase manufacturing and production capacity to support the company’s extensive portfolio of biologics medicines.

AstraZeneca plans to start staffing the facility immediately to support refurbishment and infrastructure improvements. Once complete, the site is expected to be operational and licensed for commercial production by late 2017, providing for additional capacity within the company’s biologics operations.

In the longer- term, this site could create up to 400 highly skilled jobs, subject to relevant approvals by the local authorities. The facility will eventually double the biologics manufacturing capacity in the US to meet the needs of the maturing AstraZeneca pipeline. Currently biologics make up 50 percent of the company’s pipeline with more than 120 ongoing programmes, including over 30 in clinical development.

AstraZeneca to present comprehensive data from its diabetes portfolio

AstraZeneca announced that 54 abstracts from the company’s research and development in diabetes will be presented at the 51st Annual Meeting of the European Association for the Study of Diabetes (EASD) in Stockholm, Sweden, 14-18 September 2015.

The presentations will include data on a number of approved products for the treatment of type 2 diabetes, including Forxiga® (dapagliflozin), Onglyza® (saxagliptin), Bydureon® (once-weekly exenatide extended-release for injectable suspension) and Byetta® (exenatide) injection, as well as data on the investigational combination of saxagliptin and dapagliflozin, which is currently being reviewed by the regulatory authorities in the US and EU. Additionally, several abstracts representing AstraZeneca’s early stage and pre-clinical research explore novel pathways and modalities to address the underlying pathophysiology of diabetes.

Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, said: “The breadth and depth of research we’re presenting at EASD demonstrates our continuous commitment to developing innovative diabetes treatments. We believe these data reinforce our focus to help healthcare providers and patients with type 2 diabetes reach treatment goals sooner.”

AstraZeneca Presents Evidence of AZD9291 in Non-Small Cell Lung Cancer

AstraZeneca today announced updated, encouraging data on AZD9291 (osimertinib) in first-line patients with epidermal growth factor receptor mutation (EGFRm) positive advanced non-small cell lung cancer (NSCLC) and previously treated patients with EGFR T790M mutation-positive NSCLC. The data being presented today at the World Conference on Lung Cancer (WCLC) 2015 were from the AURA Phase I trial first-line cohort and two AURA Phase II studies. 

 

Data in the first-line setting demonstrated that in 60 patients who received AZD9291 once daily 72% (95% confidence interval (CI) 58% to 82%) were progression free (PFS) at 12 months. Confirmed overall response rate (ORR) was 75% (95% CI 62% to 85%). The longest duration of response (DoR) was ongoing at 18 months.

Data on two AURA Phase II studies (AURA extension and AURA2) in previously treated patients with EGFR T790M mutation were also presented. While still preliminary, these studies showed an efficacy and tolerability profile for AZD9291 consistent with previously reported data. In AURA extension (n=201), ORR was 61% (95% CI 54% to 68%); median DoR and median PFS were not calculable (NC). Consistent results were observed in AURA2 (n=210), ORR was 71% (95% CI 64% to 77%); median DoR was 7.8 months (95% CI 7.1 months to NC) and median PFS was 8.6 months (95% CI 8.3 months to 9.7 months).

The safety profile of AZD9291 in these studies was in line with that reported earlier in the year. In the AURA first-line cohort, the most common all-cause adverse events (AE) of any grade across different dose groups included rash (grouped terms) (77% all grades, 2% Grade greater-than or equal to 3) and diarrhea (73% all grades, 3% Grade greater-than or equal to 3). These AEs were also reported as the most common in the two AURA Phase II studies (AURA extension, rash 40% all grades, 1% Grade greater-than or equal to 3, diarrhea 45% all grades, 1% Grade greater-than or equal to 3; AURA 2, rash 42% all grades, 1% Grade greater-than or equal to 3, diarrhea 39% all grades, 1% Grade greater-than or equal to 3).