On May 3, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) reported an agreement with AstraZeneca to develop companion diagnostic assays to facilitate personalized medicine in oncology by identifying patients most likely to benefit from medicines within AstraZeneca’s oncology pipeline (Press release, Foundation Medicine, MAY 3, 2016, View Source [SID:1234511843]).

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"We use companion diagnostics throughout clinical development to deliver innovative, targeted therapies to patients most likely to benefit," said Ruth March, VP and Head of Personalised Healthcare & Biomarkers at AstraZeneca. "The leading genomic profiling approach provided by Foundation Medicine can help ensure that patients are matched with therapies specifically targeted to the molecular drivers of their disease."

As part of the collaboration agreement, AstraZeneca will utilize the Quality Systems Regulations (QSR)-compliant version of Foundation Medicine’s comprehensive genomic profiling assay for solid tumors to enroll patients into clinical trials of therapies that target genomically driven mechanisms of disease. The companion diagnostic assay assesses multiple cancer-related genes as well as all four classes of genomic alterations, and will be developed in parallel with the clinical development of AstraZeneca medicines as part of a coordinated regulatory strategy.

"We’re delighted to expand our relationship with AstraZeneca to now include the development of companion diagnostics for their novel anti-cancer medicines," said Steven J. Kafka, Ph.D., President and Chief Operating Officer for Foundation Medicine. "This collaboration agreement, the fourth we have put in place with leading oncology companies, underscores the importance and potential of utilizing our rigorously validated, comprehensive profiling approach to make available to physicians an FDA-approved universal companion diagnostic solution for use with targeted medicines. We look forward to providing further updates as individual programs are initiated."

On May 3, 2016 Amgen (NASDAQ:AMGN) reported that the U.S. Food and Drug Administration (FDA) has accepted for priority review the supplemental Biologics License Application (sBLA) for BLINCYTO (blinatumomab) to include new data supporting the treatment of pediatric and adolescent patients with Philadelphia chromosome‑negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) (Press release, Amgen, MAY 3, 2016, View Source [SID:1234511825]).

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"Children and adolescents with ALL who experience a second or greater relapse or are refractory often have a dismal prognosis with survival rates below 10 percent," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The FDA’s acceptance of the sBLA submission for BLINCYTO reinforces immunotherapy as a potential option for children in need of new treatments to fight this complex disease and help prevent further relapse."

Priority review is assigned to applications for drugs that treat serious conditions and would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions. The Prescription Drug User Fee Act (PDUFA) target action date is Sept. 1, 2016.

ALL is a rare and rapidly progressing cancer of the blood and bone marrow impacting both adults and children and is the most common type of cancer in children.1-3 Of the approximately 2,500 U.S. children and adolescents diagnosed with B-cell precursor ALL each year, approximately 15-20 percent (375-500) will experience relapse or fail to achieve remission.4-7

The sBLA is based on data from the Phase 1/2 ‘205 single-arm trial, which evaluated BLINCYTO in pediatric patients with relapsed or refractory B-cell precursor ALL. The study met its Phase 2 primary endpoint of complete remission within the first two cycles of BLINCYTO treatment. Overall, the types of serious adverse events (AEs) reported in the pediatric population are consistent with the known BLINCYTO safety profile. The FDA-approved prescribing information for BLINCYTO includes a boxed warning for cytokine release syndrome and neurologic toxicities.

About Study ‘205
Study ‘205 evaluated BLINCYTO in a Phase 1/2 single-arm, multicenter, dose-finding, efficacy trial in patients less than 18 years of age with B-cell precursor ALL that was refractory, had relapsed at least twice or relapsed after an allogeneic hematopoietic stem cell transplant (alloHSCT). Treatment in this study has been completed and subjects are being monitored for long-term efficacy. The data is being submitted for publication.

This study included a Phase 1 dose-finding portion and a Phase 2 portion evaluating safety and efficacy at the recommended dose (stepwise 5/15-μg/m²/day), which was proposed by an independent Data Safety Monitoring Board based on data from the dose-finding portion. The primary Phase 1 endpoint was the maximum-tolerated dose, defined as the maximum dose at which ≤1 of six patients experienced a dose-limiting toxicity. Secondary endpoints included pharmacokinetics and incidence of AEs. The primary Phase 2 endpoint was complete remission within the first two cycles of BLINCYTO treatment. Secondary endpoints included incidence of AEs, proportion undergoing alloHSCT after BLINCYTO treatment, relapse-free survival and overall survival. Minimal residual disease (MRD) response and complete MRD response were exploratory endpoints in both phases.

The most frequent grade ≥3 AEs among the 70 patients who received the recommended dose were anemia, thrombocytopenia, febrile neutropenia, hypokalemia and neutropenia.

About BLINCYTO (blinatumomab)
BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

BLINCYTO was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration, and is now approved in the U.S. for the treatment of Ph- relapsed or refractory B-cell precursor ALL. This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.

In November 2015 BLINCYTO was granted conditional marketing authorization in the European Union for the treatment of adults with Ph- relapsed or refractory B-precursor ALL.

About BiTE Technology
Bispecific T cell engager (BiTE) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit www.biteantibodies.com.

BLINCYTO U.S. Product Safety Information

Important Safety Information Regarding BLINCYTO (blinatumomab) U.S. Indication

This safety information is specific to the current U.S. approved indication.

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Contraindications
BLINCYTO is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions
Cytokine Release Syndrome (CRS): Life-threatening or fatal CRS occurred in patients receiving BLINCYTO. Infusion reactions have occurred and may be clinically indistinguishable from manifestations of CRS. Closely monitor patients for signs and symptoms of serious events such as pyrexia, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), disseminated intravascular coagulation (DIC), capillary leak syndrome (CLS), and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Interrupt or discontinue BLINCYTO as outlined in the Prescribing Information (PI).

Neurological Toxicities: Approximately 50% of patients receiving BLINCYTO in clinical trials experienced neurological toxicities. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 15% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. The median time to onset of any neurological toxicity was 7 days. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO as outlined in the PI.

Infections: Approximately 25% of patients receiving BLINCYTO experienced serious infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO as needed.

Tumor Lysis Syndrome (TLS): Life-threatening or fatal TLS has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on treatment hydration, should be used during BLINCYTO treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO as needed to manage these events.

Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters during BLINCYTO infusion and interrupt BLINCYTO if prolonged neutropenia occurs.

Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO is being administered.

Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO treatment. The majority of these events were observed in the setting of CRS. The median time to onset was 15 days. Grade 3 or greater elevations in liver enzymes occurred in 6% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase (GGT), and TBILI prior to the start of and during BLINCYTO treatment. BLINCYTO treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.

Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO, especially in patients previously treated with cranial irradiation and anti-leukemic chemotherapy. Preparation and administration errors have occurred with BLINCYTO treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).

Adverse Reactions
The most commonly reported adverse reactions (≥ 20%) in clinical trials were pyrexia (62%), headache (36%), peripheral edema (25%), febrile neutropenia (25%), nausea (25%), hypokalemia (23%), rash (21%), tremor (20%), diarrhea (20%) and constipation (20%).

Serious adverse reactions were reported in 65% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia, pyrexia, pneumonia, sepsis, neutropenia, device-related infection, tremor, encephalopathy, infection, overdose, confusion, Staphylococcal bacteremia, and headache.

U.S. Dosage and Administration Guidelines
BLINCYTO is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm. It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).

Please see full U.S. Prescribing Information and medication guide for BLINCYTO at www.BLINCYTO.com.

On May 3, 2016 Pfizer Inc. (NYSE: PFE) reported financial results for first-quarter 2016 and updated certain components of its 2016 financial guidance (Press release, Pfizer, MAY 3, 2016, View Source [SID:1234511822]).

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On September 3, 2015, Pfizer acquired Hospira, Inc. (Hospira). Consequently, first-quarter 2016 financial results include three months of legacy Hospira global operations while first-quarter 2015 financial results do not include any contribution from legacy Hospira operations.

The Company manages its commercial operations through two distinct businesses: an Innovative Products(3) business and an Established Products(3) business. The Innovative Products(3) business is composed of two operating segments: the Global Innovative Pharmaceutical segment (GIP) and the Global Vaccines, Oncology and Consumer Healthcare segment (VOC). The Established Products(3) business consists of the Global Established Pharmaceutical segment (GEP), which includes all legacy Hospira commercial operations. Financial results for each of these segments are presented in the Operating Segment Information section.

Some amounts in this press release may not add due to rounding. All percentages have been calculated using unrounded amounts. References to operational variances pertain to period-over-period growth rates that exclude the impact of foreign exchange as well as the negative currency impact related to Venezuela. Results for first-quarter 2016 and 2015 are summarized below.

OVERALL RESULTS

($ in millions, except
per share amounts)
First-Quarter
2016 2015 Change
Reported Revenues(1) $ 13,005 $ 10,864 20%
Adjusted Income(2) 4,155 3,196 30%
Adjusted Diluted EPS(2) 0.67 0.51 32%
Reported Net Income(1) 3,016 2,376 27%
Reported Diluted EPS(1) 0.49 0.38 29%


REVENUES

($ in millions) First-Quarter
2016 2015 % Change
Total Oper.
Innovative Products(3) $ 7,033 $ 5,738 23% 28%
GIP 3,640 3,075 18% 25%
Global Vaccines 1,570 1,328 18% 22%
Global Oncology 1,001 528 90% 95%
Consumer Healthcare 822 808 2% 10%
Established Products(3)(4) $ 5,972 $ 5,125 17% 24%
GEP(4) Standalone 4,773 5,125 (7%) 1%
Legacy Hospira 1,199 — * *
Total Company $ 13,005 $ 10,864 20% 26%

Pfizer Standalone
(Excl. Legacy Hospira)
$ 11,806 $ 10,864 9% 15%

* Indicates calculation not meaningful.

SELECTED TOTAL COMPANY ADJUSTED COSTS AND EXPENSES(2)

($ in millions)
(Favorable)/Unfavorable
First-Quarter
2016 2015
% Change
Total Oper.
Cost of Sales(2) $ 2,565 $ 1,807 42% 45%
Percent of Revenues(1) 19.7 % 16.6 % N/A N/A
SI&A Expenses(2) 3,368 3,078 9% 14%
R&D Expenses(2) 1,723 1,877 (8%) (8%)
Total $ 7,656 $ 6,762 13% 16%

Effective Tax Rate(2) 23.8 % 24.4 %


2016 FINANCIAL GUIDANCE(5)

The ranges for certain components of Pfizer’s 2016 financial guidance have been updated today as set forth below, primarily reflecting the following:

Operational Factors: Strong performance to date coupled with an improved business outlook for 2016, which favorably impacted the midpoint of the guidance range for reported revenue(1) by approximately $1.0 billion and for reported(1) and adjusted(2) diluted EPS by $0.12.
Foreign Exchange: Favorable changes in foreign exchange rates since mid-January 2016, which favorably impacted the midpoint of the guidance range for reported revenue(1) by approximately $1.0 billion and for reported(1) and adjusted(2) diluted EPS by $0.06.
Pfizer’s complete 2016 financial guidance, including today’s updates, is summarized below:

Reported Revenues(1) $51.0 to $53.0 billion
(previously $49.0 to $51.0 billion)
Adjusted Cost of Sales(2) as a Percentage of Reported Revenues(1) 21.0% to 22.0%
Adjusted SI&A Expenses(2) $13.7 to $14.7 billion
(previously $13.2 to $14.2 billion)
Adjusted R&D Expenses(2) $7.4 to $7.8 billion
(previously $7.3 to $7.8 billion)
Adjusted Other (Income)/Deductions(2) Approximately ($500 million) of income
(previously approx. ($300 million) of income)
Effective Tax Rate on Adjusted Income(2) Approximately 24.0%
Reported Diluted EPS(1) $1.72 to $1.85
(previously $1.54 to $1.67)
Adjusted Diluted EPS(2) $2.38 to $2.48
(previously $2.20 to $2.30)

EXECUTIVE COMMENTARY

Ian Read, Chairman and Chief Executive Officer, stated, "We began the year with very strong operational performance across both our Innovative and Established businesses and this has served as a key driver of an increase in both our revenue and earnings per share guidance for the remainder of the year. I believe this performance results from our Company being well positioned in terms of product portfolio, organizational structure and leadership, as well as by our continued strong financial flexibility. In addition, our late stage product pipeline is increasingly ready to deliver our next set of prospective growth drivers with competitive positions in high-potential therapeutic areas where I believe Pfizer can be a leader.

"In addition, we have made excellent progress integrating the legacy Hospira operations and now expect to achieve $1.0 billion of Hospira cost savings by 2018, 25% more than our initial cost savings target of $800 million. Overall, we remain focused on delivering continued revenue growth both through internal and external opportunities, managing an efficient operating structure and making shareholder-friendly capital allocation and business portfolio decisions," Mr. Read concluded.

Frank D’Amelio, Chief Financial Officer, stated, "Overall, I am very pleased with our first-quarter 2016 financial results and with our ability to continue delivering shareholder value through prudent capital allocation. We grew revenues by 15% operationally, excluding the impact of foreign exchange and legacy Hospira operations. We also continued to deliver significant value directly to shareholders by paying $1.9 billion in first-quarter 2016 dividends and executing a $5 billion accelerated share repurchase agreement in March 2016.

"We raised our 2016 financial guidance for reported revenues(1) and adjusted diluted EPS(2) to reflect the strong operational performance to date coupled with an improved business outlook for 2016. Changes in foreign exchange rates since mid-January 2016 also favorably impacted our updated guidance. For the remainder of 2016, we expect to continue to advance the Hospira integration while remaining focused on delivering strong operating results," Mr. D’Amelio concluded.

QUARTERLY FINANCIAL HIGHLIGHTS (First-Quarter 2016 vs. First-Quarter 2015)

Reported revenues(1) totaled $13.0 billion, an increase of $2.1 billion, or 20%, which reflects operational growth of $2.9 billion, or 26%, partially offset by the unfavorable impact of foreign exchange of $729 million, or 7%. Excluding the impact of legacy Hospira operations of $1.2 billion and foreign exchange, Pfizer-standalone revenues increased by $1.7 billion operationally, or 15%. Compared with the prior-year quarter, first-quarter 2016 revenues were favorably impacted by approximately $900 million as a result of first-quarter 2016 having five additional selling days in the U.S. and four additional selling days in international markets. This imbalance in selling days will be offset in fourth-quarter 2016 resulting in essentially the same number of selling days in full-year 2016 as 2015.

Operational revenue growth in developed markets was driven primarily by the inclusion of $1.1 billion of revenues from legacy Hospira operations and continued strong performance of several key products, notably Ibrance, Prevnar 13, Eliquis, Xeljanz and Lyrica — all primarily in the U.S. In emerging markets, revenues increased 14% operationally, favorably impacted by the addition of legacy Hospira operations, which contributed $78 million, as well as the performance of Enbrel, Prevenar 13 and continued strong volume growth from certain other products.

Operational revenue growth was partially offset primarily by the loss of exclusivity and associated generic competition for Zyvox, primarily in the U.S. and certain developed Europe markets, and Lyrica in certain developed Europe markets.

Innovative Products(3) Business Highlights

Revenues for the Innovative Products(3) business increased 28% operationally, reflecting the following:

GIP revenues increased 25% operationally, primarily due to strong operational growth from Eliquis globally, Lyrica and Xeljanz both primarily in the U.S., Enbrel in most international markets and Chantix primarily in the U.S. Operational growth was slightly offset by the expiration of the collaboration agreement to co-promote Rebif in the U.S., which expired at the end of 2015.
VOC revenues increased 33% operationally, reflecting the following:
Global Vaccines revenues increased 22% operationally, driven by growth from Prevnar 13, primarily in the U.S., reflecting the timing of government purchases for the pediatric indication and continued strong uptake among adults due to the overall success of commercial programs.
Global Oncology revenues increased 95% operationally, primarily driven by continued strong momentum following the February 2015 U.S. launch of Ibrance for advanced breast cancer and, to a lesser extent, stronger demand for Sutent and Xalkori in most markets.
Consumer Healthcare revenues increased 10% operationally, primarily due to Nexium 24HR and Advil, both in the U.S., reflecting strong demand following increased promotion and the launch of a tablet form for Nexium 24HR in first-quarter 2016.
Established Products(3)(4) Business Highlights

GEP(4) revenues increased 24% operationally due to the inclusion of legacy Hospira operations, which contributed $1.2 billion, partially offset by the loss of exclusivity and associated generic competition for certain Peri-LOE Products(6), primarily Zyvox in the U.S. and certain developed Europe markets as well as Lyrica in certain developed Europe markets. Revenues excluding the contribution from the legacy Hospira portfolio (GEP(4) Standalone) increased 1% operationally, reflecting 7% operational growth from Legacy Established Products(6) and 11% operational growth from the Sterile Injectable Pharmaceuticals(6) portfolio, partially offset by an 18% operational decline from Peri-LOE Products(6). GEP(4) revenues in emerging markets increased 10% operationally, driven by the inclusion of legacy Hospira operations and reflecting operational growth from Legacy Established Products(6) and the GEP(4) Standalone Sterile Injectable Pharmaceuticals(6) portfolio.

Income Statement Highlights

Adjusted cost of sales(2), adjusted SI&A expenses(2) and adjusted R&D expenses(2) in the aggregate increased $1.1 billion operationally, or 16%, reflecting the inclusion of legacy Hospira operations in first-quarter 2016 and the following Pfizer-standalone operational factors:
higher adjusted cost of sales(2) primarily due to higher sales volumes;
higher adjusted SI&A expense(2), primarily reflecting higher general and administrative expenses as well as increased investments to support certain recently launched products and other in-line biopharmaceutical products; and
lower adjusted R&D expense(2), primarily reflecting the non-recurrence of a $295 million upfront payment to OPKO Health, Inc. in first-quarter 2015 associated with a worldwide development and commercialization agreement.

The effective tax rate on adjusted income(2) declined 0.6 percentage points to 23.8% from 24.4%. This decline was primarily due to a favorable change in the jurisdictional mix of earnings, an increase in tax benefits associated with the resolution of certain tax positions pertaining to prior years with various foreign tax authorities, as well as an increase in tax benefits due to the permanent extension of the U.S. R&D tax credit on December 18, 2015.

The diluted weighted-average shares outstanding declined by 78 million shares compared to the prior-year quarter due to Pfizer’s share repurchase program, including the impact of a $5 billion accelerated share repurchase agreement executed in February 2015 and completed in July 2015 and another reduction of 136 million shares associated with an accelerated share repurchase agreement executed in March 2016.

In addition to the aforementioned factors, first-quarter 2016 reported earnings were primarily impacted by the following:

Favorable impacts:
a lower effective tax rate, primarily due to tax benefits related to the final resolution (pending court approval) of an agreement in principle reached in February 2016 to resolve certain claims related to Protonix and tax benefits associated with our Venezuela operations, partially offset by an unfavorable change in the jurisdictional mix of earnings; and
lower charges incurred during first-quarter 2016 for business and legal entity alignment activities compared with the prior-year quarter.

Unfavorable impacts:

higher acquisition-related costs, legal charges and purchase accounting adjustments in first-quarter 2016 compared with the prior-year quarter; and
higher asset impairment charges associated with losses on certain equity-method investments in first-quarter 2016.

RECENT NOTABLE DEVELOPMENTS

Product Developments

Chantix/Champix (varenicline) — In April 2016, Pfizer announced publication in The Lancet of results from the largest clinical trial of approved smoking cessation medicines, called EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study). This smoking cessation trial included 8,144 adult smokers and was designed to compare the neuropsychiatric safety of Chantix/Champix (varenicline) and bupropion with placebo and nicotine patch in adult smokers with and without a history of psychiatric disorders. The authors concluded that the trial did not show a significant increase in serious neuropsychiatric adverse events with Chantix/Champix or bupropion compared to placebo and nicotine patch. There were more neuropsychiatric adverse events in the psychiatric cohort than the non-psychiatric cohort across all treatment arms including placebo. Results also showed that smokers treated with Chantix/Champix had significantly higher quit rates than those treated with bupropion, nicotine patch or placebo. Full results of the EAGLES trial were published in The Lancet on April 22, 2016.

Ibrance (palbociclib)
In April 2016, Pfizer announced positive top-line results from the Phase 3 PALOMA-2 trial for Ibrance. The study met its primary endpoint by demonstrating an improvement in progression-free survival (PFS) for the combination of Ibrance plus letrozole compared with letrozole plus placebo in post-menopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer who had not received previous systemic treatment for their advanced disease. The PALOMA-2 trial provides confirmatory evidence for Ibrance in combination with letrozole in the first-line setting, which was first studied in the Phase 2 PALOMA-1 trial. These data will support additional planned global regulatory submissions and a request for conversion of the accelerated approval for Ibrance to regular approval in the U.S. Detailed efficacy and safety results from the PALOMA-2 trial will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Annual Meeting.

Pfizer announced in February 2016 that the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) expanding the use of Ibrance 125 mg capsules to include the treatment of hormone receptor-positive, HER2- advanced or metastatic breast cancer in combination with fulvestrant in women with disease progression following endocrine therapy.

Inflectra (infliximab-dyyb) — In April 2016, the FDA approved Celltrion’s Inflectra (infliximab-dyyb) across all eligible indications of the reference product, Remicade(7) (infliximab). Inflectra is now the first and only biosimilar monoclonal antibody therapy to be approved in the U.S. Hospira, now a Pfizer company, entered into an agreement with Celltrion Inc. and Celltrion Healthcare, Co., Ltd. in 2009 for several potential biosimilar products, including Inflectra. As a result, Pfizer holds exclusive commercialization rights to Inflectra in the U.S.

Xalkori (crizotinib) — Pfizer announced in March 2016 that the FDA approved a sNDA for Xalkori to treat patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are ROS1-positive. Additionally, the European Medicines Agency (EMA) is reviewing an application to extend the marketing authorization of Xalkori to include the treatment of adult patients with ROS1-positive advanced NSCLC.

Xeljanz (tofacitinib citrate)
Pfizer announced in April 2016 top-line results from its first Phase 3 study investigating tofacitinib for the treatment of psoriatic arthritis (PsA), Oral Psoriatic Arthritis triaL (OPAL) Broaden. This study evaluated the efficacy and safety of tofacitinib 5 mg and 10 mg twice daily (BID) in adult patients with active PsA who had an inadequate response to at least one conventional synthetic disease-modifying antirheumatic drug and who were tumor necrosis factor inhibitor-naïve. OPAL Broaden met its primary efficacy endpoints demonstrating that both tofacitinib 5 mg BID and 10 mg BID were superior to treatment with placebo at 3 months as measured by American College of Rheumatology 20 response and Health Assessment Questionnaire Disability Index score. Overall safety findings in this study were consistent with those observed in the broader rheumatology clinical development program for tofacitinib.

In March 2016, Pfizer announced that the EMA has accepted for review the Marketing Authorization Application for Xeljanz 5 mg tablets twice daily for the treatment of patients with moderate to severe rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate (MTX).

In February 2016, Pfizer announced that the FDA has approved Xeljanz XR extended-release 11 mg tablets for the once-daily treatment of moderate to severe RA in patients who have had an inadequate response or intolerance to MTX. Xeljanz XR is the first and only once-daily oral RA treatment in its class, known as Janus kinase (JAK) inhibitors.

Pipeline Developments

A comprehensive update of Pfizer’s development pipeline was published today and is now available at www.pfizer.com/pipeline. It includes an overview of Pfizer’s research and a list of compounds in development with targeted indication and phase of development, as well as mechanism of action for candidates from Phase 2 through registration.

Avelumab (MSB0010718C) — Merck KGaA, Darmstadt, Germany (Merck KGaA) and Pfizer announced in April 2016 the treatment of the first patient in a Phase 3 study of avelumab, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, in an advanced renal cell carcinoma (RCC) setting. The study, JAVELIN Renal 101, is the first pivotal trial investigating avelumab in combination with Inlyta (axitinib), Pfizer’s tyrosine kinase inhibitor (TKI), in patients with previously untreated advanced RCC, and the only Phase 3 trial currently evaluating an anti-PD-L1 immunotherapy in combination with a vascular endothelial growth factor-receptor TKI in this setting. JAVELIN Renal 101 is a multicenter, international, randomized (1:1), open-label trial designed to evaluate the potential superiority, assessed by PFS, of first-line avelumab combined with Inlyta compared with Sutent (sunitinib malate) monotherapy, Pfizer’s oral, small-molecule, multi-targeted receptor TKI, in patients with unresectable, locally advanced or metastatic RCC with clear cell component. The study is expected to enroll 583 patients across approximately 170 sites in Asia, Europe, Latin America and North America.

Bococizumab (PF-04950615, RN316)
Pfizer announced in April 2016 the completion of patient enrollment for the global SPIRE-2 cardiovascular outcome trial for bococizumab, an investigational Proprotein Convertase Subtilisin Kexin type 9 inhibitor (PCSK9i). SPIRE-2 is evaluating the efficacy and safety of bococizumab compared to placebo in reducing the risk of major cardiovascular events among 10,600 patients at high risk for cardiovascular disease – including those without a prior history of cardiovascular events – who are on highly-effective statins or with documented statin intolerance. Many factors impact the duration of cardiovascular outcome studies, including that they are time-to-event trials, which can make it difficult to predict when the studies will accrue the required number of events. Based on current estimates, the SPIRE-2 study is expected to complete in the second half of 2017.

In April 2016, Pfizer announced positive top-line results from the second of six Phase 3 studies evaluating the low-density lipoprotein cholesterol (LDL-C) reduction activity of bococizumab. The SPIRE-AI (AutoInjector) trial of bococizumab administered with a pre-filled pen met its co-primary endpoints: percent change from baseline in LDL-C reduction at 12 weeks compared to placebo and proportion of patients successfully operating the pre-filled pen. The results of the SPIRE-AI trial are expected to be part of a potential regulatory filing for bococizumab.

Corporate Developments

In April 2016, Pfizer announced that the merger agreement between Pfizer and Allergan plc (Allergan) entered into on November 22, 2015 was terminated by mutual agreement of the companies. The decision was driven by the actions announced by the U.S. Department of Treasury on April 4, 2016, which the companies concluded qualified as an "Adverse Tax Law Change" under the merger agreement. In connection with the termination of the merger agreement, on April 8, 2016 (which falls into Pfizer’s second fiscal quarter), Pfizer paid Allergan $150 million for reimbursement of Allergan’s expenses associated with the terminated transaction.

Pfizer announced in March 2016 that it entered into an accelerated share repurchase agreement with Goldman, Sachs & Co. (GS&Co.) to repurchase $5 billion of Pfizer’s common stock. Pursuant to the terms of the agreement, on March 10, 2016, Pfizer paid $5 billion to GS&Co. and received an initial delivery of approximately 136 million shares of Pfizer common stock from GS&Co. At settlement of the agreement, which is expected to occur during the second quarter of 2016, GS&Co. may be required to deliver additional shares of common stock to Pfizer, or, under certain circumstances, Pfizer may be required to deliver shares of its common stock or may elect to make a cash payment to GS&Co., with the number of shares to be delivered or the amount of such payment based on the volume-weighted average price, less a discount, of Pfizer’s common stock during the term of the transaction.
Pfizer reported in February 2016 that its Wyeth subsidiary reached an agreement in principle to resolve claims alleging that Wyeth’s practices relating to the calculation of Medicaid rebates for its drug Protonix (pantoprazole sodium) between 2001 and 2006, several years before Pfizer acquired Wyeth in 2009, violated the Federal Civil False Claims Act and other laws. As a result, in February 2016, Pfizer reissued its fourth-quarter and full-year 2015 financial results prepared in accordance with U.S. generally accepted accounting principles (GAAP) to reflect a charge of $784.6 million. In April 2016, this agreement was finalized and Wyeth made a payment of this amount to resolve these claims. The final agreement is subject to court approval and does not include an admission of liability by Wyeth. As previously mentioned, a tax benefit related to this resolution was recorded in Pfizer’s first-quarter 2016 GAAP financial results.

On May 3, 2016 ONCODESIGN (Alternext: ALONC) and Ipsen (Euronext: IPN; ADR: IPSEY) reported that they have entered into a strategic partnership in oncology (Press release, Ipsen, MAY 3, 2016, View Source [SID:1234511801]).

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Under this new agreement, Oncodesign will handle pre-clinical pharmacology for Ipsen’s oncology research programs. In addition, some of Oncodesign’s teams are moving to Ipsen’s largest R&D center at the Paris-Saclay hub, putting them at the heart of an ecosystem made up of research scientists, leading educational institutions, research facilities and cutting-edge industrial groups. For the past 20 years, Oncodesign and Ipsen have worked together on R&D projects based on a service and co-development relationship, before sealing a drug discovery partnership in 2012.

Claude Bertrand, Ipsen’s Executive Vice-President, R&D and Chief Scientific Officer, said: "Ipsen has decided to locate its three R&D centers at the heart of the world’s top competitiveness clusters in the life sciences industry (Paris-Saclay in France, Oxford in the United Kingdom, and Cambridge in the United States) to step up the pace of discovery of innovative new drugs." Christophe Thurieau, Ipsen Innovation’s Senior Vice-President, Worldwide Scientific Affairs, added: "This partnership with Oncodesign fits perfectly with the development of Ipsen’s new R&D model, in which our Paris-Saclay platform will become a private open innovation campus. Oncodesign has renowned expertise in oncology, and we are delighted to have them join us at our Innovation Campus."

"Oncodesign is honored to have been chosen as a key strategic partner of Ipsen. This is testimony to the innovative nature of the technologies we have been developing for several years", stated Philippe Genne, CEO of Oncodesign. "Oncodesign has long been involved in the development of new economic and social models that meet the current and future challenges raised by innovation in the life sciences. Directly in keeping with our collective commitment within AFSSI1 , we are proud to be able to play our part in accelerating the development of Ipsen’s innovation campus in Paris-Saclay. This new concept aims to foster innovation by bringing together organizations with different cultures. Oncodesign will also gain access to new skills and expertise critical for the development of new therapies, including in pharmacology and the development of biomarkers."

Ipsen will use experimental models and new pharmacological approaches based on Oncodesign’s pharmaco-imaging and the detection of biomarkers. This new partnership represents a shift from a collaborative model that has already proven its value to a more extensive collaboration over a renewable 5-year term through the creation of a joint research team based both at Ipsen’s Les Ulis facility and Oncodesign’s facility in Dijon.

As part of this collaboration, Oncodesign will receive a minimum guaranteed annual fee to cover the cost of its research efforts at Les Ulis and of its Dijon platform, to which variable payments, linked to business volumes generated by Ipsen’s programs, may be added.