From Pfizer:

TRUMENBA® (Meningococcal Group B Vaccine) is Now Available

Tuesday, November 18, 2014 8:30 am EST

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PFE

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"We have been working around the clock since TRUMENBA was approved by the U.S. Food and Drug Administration on October 29 to supply TRUMENBA in the U.S., as the most frequent question we have been asked following approval is when the vaccine would be available here"

NEW YORK--(BUSINESS WIRE)--Pfizer Inc. (NYSE:PFE) announced today that TRUMENBA®(Meningococcal Group B Vaccine), the first and only FDA-approved vaccine for active immunization to prevent invasive disease caused by Neisseria meningitidis serogroup B in individuals 10 through 25 years of age, is now available for order by healthcare providers in the United States.

Serogroup B meningococcal meningitis is characterized by high fatality rates and rapid onset, often within 24 hours. For individuals 11-24 years of age, approximately 30 percent of meningococcal disease is serogroup B in the U.S., and 10 percent of these cases result in death.1 As many as 60 percent of adolescent survivors of meningococcal disease, 15-19 years of age, suffer from permanent life altering consequences such as hearing loss, neurologic damage, or loss of a limb.2

“We have been working around the clock since TRUMENBA was approved by the U.S. Food and Drug Administration on October 29 to supply TRUMENBA in the U.S., as the most frequent question we have been asked following approval is when the vaccine would be available here,” said Susan Silbermann, president and general manager, Pfizer Vaccines. “As of November 18, TRUMENBA is available for order by healthcare providers, retail pharmacies, hospitals and college health centers who may be interested in stocking and administering the vaccine. We continue to work very closely with the CDC’s Advisory Committee on Immunization Practices to help inform discussions and potential recommendations regarding prevention of meningococcal group B disease through vaccination, an important step to improve access to TRUMENBA and help in the prevention of such a devastating disease.”

Orders for TRUMENBA may be placed by contacting Pfizer Customer Service at 1-800-666-7248. Stock is currently available to begin shipping to retail pharmacies, hospitals, physician’s offices, college health centers and other medical practices. Availability for those who seek vaccination will vary by provider stocking.

For the full prescribing information for TRUMENBA, please visit www.pfizer.com.

U.S. Indication for TRUMENBA® (meningococcal group B vaccine)

TRUMENBA (Meningococcal Group B Vaccine) is indicated for active immunization to prevent invasive disease caused by Neisseria meningitidis serogroup B in individuals aged 10 through 25 years of age. Approval of TRUMENBA is based on the demonstration of immune response, as measured by serum bactericidal activity against four serogroup B strains representative of prevalent strains in the United States. The effectiveness of TRUMENBA against diverse serogroup B strains has not been confirmed.

Important Safety Information

• TRUMENBA should not be given to anyone with a history of a severe allergic reaction after a previous dose of TRUMENBA.
• Individuals with weakened immune systems may have a reduced immune response.
• The most common adverse reactions were pain at the injection site, fatigue, headache, muscle pain, and chills.
• Data are not available on the safety and effectiveness of using TRUMENBA and other meningococcal group B vaccines interchangeably to complete the vaccination series.
• Tell your healthcare provider if you are pregnant, or plan to become pregnant.
• Ask your healthcare provider about the risks and benefits of TRUMENBA. Only a healthcare provider can decide if TRUMENBA is right for you or your child.

You are encouraged to report negative side effects of vaccines to the U.S. Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC). Visit www.vaers.hhs.gov or call 1-800-822-7967.

About TRUMENBA® (meningococcal group B vaccine)

TRUMENBA is a sterile suspension composed of two recombinant lipidated factor H binding protein (fHBP) variants from N. meningitidisserogroup B, one from fHBP subfamily A and one from subfamily B (A05 and B01, respectively). fHBP is one of many proteins found on the surface of meningococci and contributes to the ability of the bacterium to avoid host defenses. fHBPs can be categorized into two immunologically distinct subfamilies, A and B. The susceptibility of serogroup B meningococci to complement-mediated, antibody-dependent killing following vaccination with TRUMENBA is dependent on both the antigenic similarity of the bacterial and vaccine fHBPs, as well as the amount of fHBP expressed on the surface of the invading meningococci.3

As with any vaccine, TRUMENBA may not prevent disease in all vaccinated individuals. The frequency of meningococcal disease caused by serogroup B varies geographically, and could influence the ability to evaluate effectiveness of the vaccine in any given country. Based on the low incidence of meningococcal disease, placebo-controlled clinical trials for TRUMENBA were considered unfeasible due to the size of the study that would be required and were not performed. Licensure of TRUMENBA was based on demonstration of immune responses measured using a serum bactericidal assay with human complement (hSBA).

TRUMENBA was reviewed and approved under the FDA’s Breakthrough Therapy designation and Priority Review programs.

TRUMENBA is to be administered as a 3-dose series at months 0, 2 and 6 in the 10 through 25 year old age group.3

About Meningococcal B Disease

The majority of invasive meningococcal disease cases worldwide can be attributed to five Neisseria meningitidis serogroups (A, B, C, W and Y).4 In 2012, approximately 40 percent of all meningococcal disease cases in the U.S. were caused by serogroup B.5Meningococcal disease affects all age groups in the U.S., but incidence is highest among infants younger than one year, adolescents and young adults, and the elderly.6

Meningococcal disease can be unpredictable and occur quickly and without warning in otherwise healthy individuals.7,8 Outbreaks and cases of meningococcal group B disease occurred in the U.S. in 2013 and 2014.9,10,11,12

Meningococcal disease may result in life-altering, significant long-term and permanent medical disabilities.2,13,14 Despite the availability of antibiotic treatment, between 10 and 15 percent of patients with meningococcal disease die and 11 to 19 percent of those who survive are afflicted with long-term disabilities, such as brain damage, hearing loss, learning disabilities or limb amputations.15

Pfizer Inc.: Working together for a healthier world™

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world's best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us. To learn more, please visit us at www.pfizer.com.

DISCLOSURE NOTICE: The information contained in this release is as of November 18, 2014. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.

This release contains forward-looking information about TRUMENBA® (meningococcal group B vaccine), including its potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of TRUMENBA; uncertainties regarding whether and when the CDC’s Advisory Committee on Immunization Practices will make any potential recommendations regarding meningococcal group B vaccination; the uncertainties inherent in research and development, including the ability to meet anticipated clinical trial completion dates and regulatory submission dates, as well as the possibility of unfavorable clinical trial results; whether and when any biologics license applications may be filed in any jurisdictions other than the United States for TRUMENBA; whether and when any such other applications may be approved by regulatory authorities, which will depend on the assessment by such regulatory authorities of the benefit-risk profile suggested by the totality of the efficacy and safety information submitted; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of TRUMENBA; and competitive developments.

A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2013 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information That May Affect Future Results,” as well as in its subsequent reports on Form 8-K, all of which are filed with the SEC and available at www.sec.gov and www.pfizer.com.

_____________________________________________

1 Centers for Disease Control and Prevention. Prevention and Control of Meningococcal Disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2013 March 22; 62(RR02); 1-28.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6202a1.htm. Last updated March 22, 2013. Accessed November 17, 2014.

2 Borg J, Christie D, Coen PG, Pooy R, Viner RM. Outcomes of Meningococcal Disease in Adolescence: prospective, matched-cohort study. Pediatrics. 2009; 123: e502-e509.

3 TRUMENBA® (meningococcal group B vaccine Prescribing Information, Pfizer, Inc. October 2014.

4 Pinto VB, Burden R, Wagner A, Moran EE, Lee C. The Development of an Experimental Multiple Serogroups Vaccine for Neisseria meningitidis. PLoS ONE. 2013; 8(11): 1-10.

5 Centers for Disease Control and Prevention. Active Bacterial Core Surveillance (ABCs) Report Emerging Infections Program Network -Neisseria meningitidis, 2012. http://www.cdc.gov/abcs/reports-findings/survreports/mening12.html. Accessed October 27, 2014.

6 Cohn A, MacNeil JR, Harrison LH, et al. Changes in Neisseria meningitidis disease epidemiology in the United States, 1998-2007: implications for prevention of meningococcal disease. Clin Infect Dis. 2010; 50: 184-191.

7 Sáfadi MAP, McIntosh EDG. Epidemiology and prevention of meningococcal disease: a critical appraisal of vaccine policies. Expert Rev Vaccines. 2011; 10: 1717-1730.

8 Poland GA. Prevention of meningococcal disease: current use of polysaccharide and conjugate vaccines. Clin Infect Dis. 2010; 50: S45-S53.

9 Jaslow, R. CBS News. Seventh possible meningitis case reported at Princeton University. November 11, 2013.http://www.cbsnews.com/news/seventh-possible-meningitis-case-reported-at-princeton-university/. Accessed October 27, 2014.

10 Landau, E. CNN.com. 3 meningococcal disease cases at Calif. college. http://www.cnn.com/2013/11/21/health/california-students-illness/. Updated November 21, 2013. Accessed October 27, 2014.

11 Hayes, A. CNN.com. Philadelphia meningitis death tied to Princeton outbreak. http://www.cnn.com/2014/03/18/health/drexel-meningitis-death/. Updated March 18, 2014. Accessed October 27, 2014.

12 Zauzmer, J. The Washington Post. Georgetown offering preventive antibiotics to close friends of meningitis victim. September 18, 2014. http://www.washingtonpost.com/local/education/georgetown-offering-preventive-antibiotics-to-close-friends-of-meningitis-victim/2014/09/18/d6831604-3fa7-11e4-b0ea-8141703bbf6f_story.html. Accessed October 27, 2014.

13 Sabatini C, Bosis S, Semino M, Senatore L, Principi N, Esposito S. Clinical Presentation of Meningococcal Disease in Childhood. J Prev Med Hyg. 2012; 53: 116-119.

14 Brigham KS, Sandora TJ. Neisseria meningitidis: epidemiology, treatment and prevention in adolescents. Curr Opin Pediatr. 2009; 21: 437-443.

15 Centers for Disease Control and Prevention. Help Protect Your Preteen and Teen Against Meningococcal Disease.http://www.cdc.gov/features/meningococcal/. Last updated April 21, 2014. Accessed October 27, 2014.

From Bristol-Myers Squibb:

Portola, Bristol-Myers Squibb and Pfizer Announce Statistically Significant Results from the First Part of the Phase 3 ANNEXA™-A Studies of Investigational Andexanet Alfa with Eliquis (apixaban)

-- Andexanet Alfa Rapidly Reversed the Anticoagulant Effect of the Factor Xa Inhibitor Eliquis (apixaban) Among All Study Participants --

-- Data Presented Today during American Heart Association 2014 Scientific Sessions: “Clinical Science: Special Reports” Session --

Monday, November 17, 2014 8:00 am EST

Portola Pharmaceuticals (NASDAQ: PTLA), Bristol-Myers Squibb Company (NYSE: BMY) and Pfizer Inc. (NYSE: PFE) today announced results from the first part of the Phase 3 ANNEXA™-A (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors – Apixaban) studies. Andexanet alfa produced rapid and nearly complete reversal (by approximately 94 percent, p value <0.0001) of the anticoagulant effect ofEliquis (apixaban) in healthy volunteers ages 50-75. The full data set will be presented today in an oral presentation during the “Clinical Science: Special Reports” session at the American Heart Association (AHA) 2014 Scientific Sessions in Chicago, IL.  

This first part of the Phase 3 ANNEXA-A trial achieved all of its primary and secondary endpoints with statistical significance (p value <0.0001). The trial included 33 subjects, with 24 randomized to andexanet alfa and nine to placebo. In the study, two to five minutes after completion of a bolus dose of andexanet alfa, the anticoagulant activity of Eliquis was reversed by approximately 94 percent (p value <0.0001) compared with placebo as measured by anti-Factor Xa activity. Every subject treated with andexanet alfa had between 90 and 96 percent reversal of the anticoagulant activity of Eliquis. The reversal of anti-Factor Xa activity correlated with a significant reduction in the level of free, unbound Eliquis in the plasma, consistent with the mechanism of action of andexanet alfa. Additionally, andexanet alfa restored thrombin generation to baseline normal levels (prior to Eliquis therapy). In this study, no serious adverse events, thrombotic events, or antibodies to Factor X or Xa were reported following andexanet alfa administration. Mild infusion reaction was reported in three subjects.  

“The statistically significant reversal of the anticoagulant effect of Eliquis demonstrated in all subjects receiving andexanet alfa, an FDA-designated breakthrough therapy, reinforces our commitment to bring this antidote to market as quickly as possible under an Accelerated Approval pathway,” said John T. Curnutte, M.D., Ph.D., executive vice president, research and development for Portola. “Andexanet alfa is unique. Andexanet alfa rapidly reversed Anti-Xa activity with high specificity and a well-understood mechanism of action. We believe andexanet alfa could be the first universal Factor Xa inhibitor antidote available for anticoagulated patients who are experiencing a major bleeding event or those needing emergency surgery.”

“Bristol-Myers Squibb and Pfizer’s collaboration with Portola for the development and evaluation of andexanet alfa with Eliquis further demonstrates our commitment to delivering innovative therapies,” said Dr. Steven Romano, senior vice president and head, Medicines Development Group, Pfizer Global Innovative Pharmaceutical Business. “We are pleased with the positive results of this ANNEXA-A study, which demonstrated a rapid and near complete reversal of the anticoagulant effects ofEliquis. We look forward to the completion of the second part of this study.”

“Eliquis has proven to be an important treatment option for patients at risk for blood clots due to nonvalvular atrial fibrillation and venous thromboembolism,” said Douglas Manion, M.D., head of specialty development, Bristol-Myers Squibb. “Currently, there is no antidote to Eliquis. Andexanet alfa has the potential to be an effective option for patients who may require reversal of the anticoagulation effects of Eliquis.”

ANNEXA-A Study Design

The randomized, double-blind, placebo-controlled Phase 3 ANNEXA-A study is evaluating the safety and efficacy of andexanet alfa in reversing Eliquis-induced anticoagulation in older healthy volunteers ages 50-75. Efficacy is being evaluated using biomarker endpoints, including anti-Factor Xa levels as the primary endpoint. Secondary endpoints include levels of plasma unbound (free fraction) of Eliquis and thrombin generation levels.

In the first part of the ANNEXA-A study, reported today, 33 healthy volunteers (ages 50-73) were given Eliquis 5 mg twice daily for four days and then randomized in a 3:1 ratio to andexanet alfa administered as a 400 mg IV bolus (n=24) or to placebo (n=9). In the second part, 32 healthy volunteers will be given Eliquis 5 mg twice daily for four days and then randomized in a 3:1 ratio to andexanet alfa administered as a 400 mg IV bolus followed by a continuous infusion of 4 mg/min for 120 minutes or to placebo. Data from the second study are expected in early 2015.

Addressing the Absence of a Factor Xa Inhibitor Antidote

Currently, millions of patients are treated with Factor Xa inhibitors for short-term use or chronic conditions, and the anticoagulant market is expected to continue to grow. Recent patient data[i] confirm earlier clinical trial results showing that, annually, between 1-4 percent of patients treated with Factor Xa inhibitors may experience major bleeding and an additional 1 percent may require emergency surgery. Development of a specific antidote designed to reverse the anticoagulant activity of Factor Xa inhibitors may provide an important treatment option for patients who experience a major bleeding event or require emergency surgery.

About Andexanet Alfa

Andexanet alfa, an FDA-designated breakthrough therapy, is a first-in-class recombinant, modified Factor Xa molecule. It is being developed as an antidote for patients receiving a Factor Xa inhibitor who suffer a major bleeding episode or who may require emergency surgery. Andexanet alfa acts as a Factor Xa decoy that targets and sequesters with high specificity both direct and indirect Factor Xa inhibitors in the blood. Once bound, the Factor Xa inhibitors are unable to bind to and inhibit native Factor Xa, thus allowing for the restoration of normal hemostatic processes. Andexanet alfa has the potential to address numerous clinical scenarios by allowing for flexible and controlled reversal, which can be short-acting through the administration of an IV bolus or longer-acting with the addition of an extended infusion.

About the Andexanet Alfa Clinical Development Program

Portola is evaluating andexanet alfa in randomized, placebo-controlled Phase 3 ANNEXA™ (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors) registration studies using pharmacodynamic endpoints agreed to with the FDA, such as anti-Factor Xa activity, to demonstrate efficacy. These studies are designed to support the Company’s BLA filing for Accelerated Approval. As part of the Accelerated Approval process, a Phase 3b/4 confirmatory patient study evaluating clinical outcomes with andexanet alfa is planned and will be initiated prior to the BLA filing.

Results from four separate Phase 2 proof-of concept studies in healthy volunteers demonstrated that andexanet alfa immediately reversed the anticoagulation activity of four different Factor Xa inhibitors and that the reversal could be sustained. Andexanet alfa has been shown to be well tolerated in Phase 1 and 2 clinical studies, which have included more than 100 healthy volunteers, with no thrombotic events or antibodies to Factor Xa or Factor X observed.

About Eliquis

Eliquis (apixaban) is an oral selective Factor Xa inhibitor. By inhibiting Factor Xa, a key blood-clotting protein, Eliquis decreases thrombin generation and blood clot formation.Eliquis is approved for multiple indications in the U.S. based on efficacy and safety data, including results from seven Phase 3 clinical trials. Eliquis is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery; for the treatment of DVT and PE; and to reduce the risk of recurrent DVT and PE following initial therapy.

ELIQUIS Important Safety Information

WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS,  (B) SPINAL/EPIDURAL HEMATOMA (A) Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant. (B) Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: use of indwelling epidural catheters concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti‑inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants a history of traumatic or repeated epidural or spinal punctures a history of spinal deformity or spinal surgery optimal timing between the administration of ELIQUIS and neuraxial procedures is not known Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated.

CONTRAINDICATIONS

• Active pathological bleeding
• Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions)

WARNINGS AND PRECAUTIONS

• Increased Risk of Thrombotic Events after Premature Discontinuation:Premature discontinuation of any oral anticoagulant, including ELIQUIS, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from ELIQUIS to warfarin in clinical trials in atrial fibrillation patients. If ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.

• Bleeding Risk: ELIQUIS increases the risk of bleeding and can cause serious, potentially fatal bleeding.
  • Concomitant use of drugs affecting hemostasis increases the risk of bleeding including aspirin and other anti-platelet agents, other anticoagulants, heparin, thrombolytic agents, SSRIs, SNRIs, and NSAIDs.
  • Advise patients of signs and symptoms of blood loss and to report them immediately or go to an emergency room. Discontinue ELIQUIS in patients with active pathological hemorrhage.
  • There is no established way to reverse the anticoagulant effect of apixaban, which can be expected to persist for at least 24 hours after the last dose (i.e., about two half-lives). A specific antidote for ELIQUIS is not available.
  • Spinal/Epidural Anesthesia or Puncture: Patients treated with Eliquis undergoing spinal/epidural anesthesia or puncture may develop an epidural or spinal hematoma which can result in long-term or permanent paralysis.

The risk of these events may be increased by the postoperative use of indwelling epidural catheters or the concomitant use of medicinal products affecting hemostasis. Indwelling epidural or intrathecal catheters should not be removed earlier than 24 hours after the last administration of ELIQUIS. The next dose of ELIQUIS should not be administered earlier than 5 hours after the removal of the catheter. The risk may also be increased by traumatic or repeated epidural or spinal puncture. If traumatic puncture occurs, delay the administration of ELIQUIS for 48 hours.

Monitor patients frequently and if neurological compromise is noted, urgent diagnosis and treatment is necessary. Physicians should consider the potential benefit versus the risk of neuraxial intervention in Eliquis patients.

• Prosthetic Heart Valves: The safety and efficacy of ELIQUIS have not been studied in patients with prosthetic heart valves and is not recommended in these patients.

• Acute PE in Hemodynamically Unstable Patients or Patients who Require Thrombolysis or Pulmonary Embolectomy: Initiation of ELIQUIS is not recommended as an alternative to unfractionated heparin for the initial treatment of patients with PE who present with hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy.

ADVERSE REACTIONS

• The most common and most serious adverse reactions reported with ELIQUIS were related to bleeding.

TEMPORARY INTERRUPTION FOR SURGERY AND OTHER INTERVENTIONS

• ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding. ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be noncritical in location and easily controlled. Bridging anticoagulation during the 24 to 48 hours after stopping ELIQUIS and prior to the intervention is not generally required. ELIQUIS should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established.

DRUG INTERACTIONS

• Strong Dual Inhibitors of CYP3A4 and P-gp: Inhibitors of CYP3A4 and P-gp increase exposure to apixaban and increase the risk of bleeding. For patients receiving ELIQUIS doses greater than 2.5 mg twice daily, the dose of ELIQUIS should be decreased by 50% when it is coadministered with drugs that are strong dual inhibitors of CYP3A4 and P-gp (e.g., ketoconazole, itraconazole, ritonavir, or clarithromycin). For patients receiving ELIQUIS at a dose of 2.5 mg twice daily, avoid coadministration with strong dual inhibitors of CYP3A4 and P-gp.
• Strong Dual Inducers of CYP3A4 and P-gp: Avoid concomitant use of ELIQUIS with strong dual inducers of CYP3A4 and P-gp (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) because such drugs will decrease exposure to apixaban and increase the risk of stroke and other thromboembolic events.
• Anticoagulants and Antiplatelet Agents: Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding. APPRAISE-2, a placebo-controlled clinical trial of apixaban in high-risk post-acute coronary syndrome patients treated with aspirin or the combination of aspirin and clopidogrel, was terminated early due to a higher rate of bleeding with apixaban compared to placebo.

PREGNANCY CATEGORY B

• There are no adequate and well-controlled studies of ELIQUIS in pregnant women. Treatment is likely to increase the risk of hemorrhage during pregnancy and delivery. ELIQUIS should be used during pregnancy only if the potential benefit outweighs the potential risk to the mother and fetus.

Please see full Prescribing Information, including BOXED WARNINGS and Medication Guide, available at www.bms.com.

About Portola Pharmaceuticals, Inc.

Portola Pharmaceuticals is a biopharmaceutical company developing product candidates that could significantly advance the fields of thrombosis and other hematologic diseases. The Company is advancing its three wholly-owned programs using novel biomarker and genetic approaches that may increase the likelihood of clinical, regulatory and commercial success of its potentially life-saving therapies. Portola's partnered program is focused on developing selective Syk inhibitors for inflammatory conditions. 

Betrixaban

Portola’s wholly-owned, oral, once-daily Factor Xa inhibitor betrixaban is being evaluated in the only biomarker-based Phase 3 study for hospital-to-home prophylaxis of venous thromboembolism (VTE) in acute medically ill patients. Betrixaban's distinct properties may have the potential to allow the agent to demonstrate efficacy without the significant increase in the rate of major bleeding that was seen in this patient population with other Factor Xa inhibitors. If approved, betrixaban could be the first anticoagulant for both hospital and post-discharge VTE prophylaxis and the standard of care in this large market of more than 20 million patients in the G7 countries alone.        

Andexanet Alfa

Andexanet alfa, a recombinant modified human Factor Xa molecule, has the potential to be a first-in-class antidote to reverse the effects of Factor Xa inhibitors in patients who suffer a major bleeding episode or who require emergency surgery. Andexanet alfa has been designated as a breakthrough therapy by the FDA. Portola has entered into Phase 3 clinical collaboration agreements with all of the manufacturers of direct Factor Xa inhibitors while retaining all commercial rights to andexanet alfa. The Company is currently evaluating andexanet alfa in the Phase 3 ANNEXA™ (Andexanet Alfa a Novel Antidote to the Anticoagulant Effects of fXA Inhibitors) registration studies.

Cerdulatinib* (PRT2070)

Portola's product candidate in the area of hematologic cancer, cerdulatinib, is an orally available molecule that uniquely inhibits two validated tumor proliferation pathways – spleen tyrosine kinase (Syk) and janus kinase (JAK). It is currently being evaluated in a Phase 1/2a proof-of-concept study in patients with B cell leukemias or lymphomas with a focus on genetically-defined subtypes, as well as in patients who have failed therapy due to relapse or acquired mutations.

For more information, visit www.portola.com and follow the Company on Twitter @Portola_Pharma.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

About Pfizer Inc.: Working together for a healthier world™

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world's best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us. To learn more, please visit us at www.pfizer.com. 

Portola Forward-Looking Statement

Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: Portola's plans for future clinical studies, timing of clinical study results, future regulatory filings and pursuit of an accelerated approval process for andexanet alfa, anticipated growth in the market for anticoagulants, and the potential efficacy, safety and activity of Portola’s product candidates. Risks that contribute to the uncertain nature of the forward-looking statements include: the accuracy of Portola's estimates regarding its ability to initiate and/or complete its clinical trials; the success of Portola's clinical trials and the demonstrated efficacy of Portola's product candidates thereunder; the accuracy of Portola's estimates regarding its expenses and capital requirements; Portola’s ability to manufacture andexanet alfa; regulatory developments in the United States and foreign countries; Portola's ability to obtain and maintain intellectual property protection for its product candidates; and the loss of key scientific or management personnel. These and other risks and uncertainties are described more fully in Portola’s most recent filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K and most recent Quarterly Report on Form 10-Q. All forward-looking statements contained in this press release speak only as of the date on which they were made. Portola undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Bristol-Myers Squibb Forward-Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding product development. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2013, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

Pfizer Disclosure Notice

The information contained in this release is as of November 17, 2014. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.

This release contains forward-looking information about Eliquis and andexanet alfa, including their potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the possibility of unfavorable clinical trial results, including unfavorable new clinical data and additional analyses of existing clinical data; whether and when any BLA may be filed for andexanet alfa; whether and when regulatory authorities will approve any such BLA; and competitive developments.

A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2013 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the SEC and available at www.sec.gov and www.pfizer.com.

# # #

*Cerdulatinib is a proposed International Nonproprietary Name (pINN).

[i] Source: Truven MARKETSCAN^® Commercial, Medicare Supplemental and Medicaid Database (12 months ending September 2013).

From Pfizer:

Pfizer Forms Global Strategic Alliance with Merck KGaA, Germany, to Jointly Develop and Commercialize Anti-PD-L1 to Accelerate Presence in Immuno-Oncology

PD-L1 Antibody Clinical Results Consistent with Class; Interim Data Demonstrated A Complete and Partial Responses in Ovarian Cancer and NSCLC

Up to 20 High Priority Immuno-Oncology Clinical Development Programs, Including Up to 6 Registration Trials, Expected to Commence in 2015

Updates 2014 Reported Diluted EPS Range Solely to Reflect the Transaction

Analyst Call Scheduled for 10 a.m. EST on Monday, November 17, 2014

Monday, November 17, 2014 2:53 am EST

Dateline:

NEW YORK

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Public Company Information:

NYSE:

PFE

US7170811035

"On top of that, the global alliance will enable Merck to gain an early entry into the US oncology market as well as to strengthen our existing oncology business in several other important global markets."

NEW YORK--(BUSINESS WIRE)--Pfizer Inc. (NYSE:PFE) announced today that it has entered into an agreement with Merck KGaA, Darmstadt, Germany, to jointly develop and commercialize MSB0010718C, an investigational anti-PD-L1 antibody currently in development by Merck KGaA as a potential treatment for multiple types of cancer. Pfizer and Merck KGaA will explore the therapeutic potential of this novel anti-PD-L1 antibody as a single agent as well as in various combinations with Pfizer’s and Merck KGaA’s broad portfolio of approved and investigational oncology therapies.

Building on the ongoing Phase 1 program that has treated more than 550 patients, both companies will collaborate on up to 20 high priority immuno-oncology clinical development programs expected to commence in 2015. These clinical development programs include up to six trials (Phase 2 or 3) that could be pivotal for potential product registrations.

“This global alliance enables Pfizer and Merck KGaA to join forces and combine complementary strengths with the goal of meeting the needs of patients with multiple types of cancer,” said Albert Bourla, group president Vaccines, Oncology and Consumer Healthcare Businesses, Pfizer. “Immuno-oncology is a top priority for Pfizer. Combining this promising anti-PD-L1 antibody with Pfizer’s extensive portfolio of small molecules and antibodies, provides an opportunity to potentially broaden the use of immunotherapy for patients with cancer and rapidly expand our oncology business. In addition, this alliance enables us to significantly accelerate the timeframe of our development programs and move into the first wave of potential immuno-oncology based treatment regimens.”

“Collaborating globally with Pfizer will allow us to benefit from the strengths and capabilities of both companies in immuno-oncology, further accelerating this promising asset in the race to address the needs of cancer patients across multiple tumor types. Up to 20 high priority immuno-oncology clinical development programs are expected to commence in 2015, including pivotal registration studies,” continued Belén Garijo, president and chief executive officer of Merck’s biopharmaceutical division Merck Serono and Executive Board Member Elect. “On top of that, the global alliance will enable Merck to gain an early entry into the US oncology market as well as to strengthen our existing oncology business in several other important global markets.”

There are currently two clinical development programs underway evaluating Merck KGaA’s anti-PD-L1 antibody. In a Phase 1 trial, more than 550 patients have been treated with MSB0010718C across multiple types of cancers. As part of the Analyst and Investor Day hosted by Merck KGaA on September 18, 2014, interim data were presented from an ongoing Phase 1 study demonstrating a complete response and partial responses in patients with non-small cell lung cancer and ovarian cancer. Additional data are expected to be presented at medical congresses in 2015. There is also an ongoing Phase 2 trial evaluating this antibody in patients with metastatic Merkel cell carcinoma, a rare form of skin cancer. For more information, please visit www.clinicaltrials.gov.

“Early results for Merck KGaA’s PD-L1 in patient trials are impressive and consistent with the results seen with the class of PD-1 and PD-L1 antibodies,” said Mikael Dolsten, M.D., Ph.D., president of Pfizer Worldwide Research and Development (WRD) and executive vice president, Pfizer. “This promising foundation of research will form the basis of multiple registration trials.”

Separate from the PD-L1 programs, Pfizer and Merck KGaA will also combine resources and expertise to advance Pfizer’s anti-PD-1 antibody into Phase 1 trials. The parties have also agreed to co-promote Pfizer’s XALKORI in the United States and several other key markets.

Under the terms of the agreement, Merck KGaA will receive an upfront payment of $850 million and is eligible to receive regulatory and commercial milestone payments up to approximately $2 billion. Both companies will jointly fund all development and commercialization costs and all revenues obtained from selling any anti-PD-L1 or anti-PD-1 products generated from this collaboration will be shared equally.

As a result of this transaction, Pfizer will recognize this upfront payment as a certain significant item which will impact Reported Diluted earnings per share or EPS.(*) Pfizer is updating its previous 2014 Reported Diluted EPS guidance range from $1.50 - $1.59 to $1.40 - $1.49, while maintaining the other elements of its 2014 financial guidance.(**)

Our updated 2014 financial guidance does not reflect the additional impact of the exchange of future profits of Xalkori which will be measured at fair value and will reduce our 2014 reported financial results as the fair value is currently being determined. Our current expectation is that it may be between $250-$400 million on a pre-tax basis as we have not concluded our analysis of this component as of this date.

Pfizer Inc. invites investors and the general public to view and listen to a webcast of a live conference call with investment analysts at 10 a.m. EST on Monday, November 17, 2014.

To view and listen to the webcast visit our web site at www.pfizer.com and click on the “Pfizer Immuno-Oncology Strategic Alliance Announcement” link in the For Investors section located on the lower right-hand corner of that page. Information on accessing and pre-registering for the webcast will be available at www.pfizer.com beginning today. Participants are advised to pre-register in advance of the conference call.

You can also listen to the conference call by dialing either 866-246-2545 in the United States and Canada or 706-634-2365 outside of the United States and Canada. The password is “Investors”. Please join the call five minutes prior to the start time to avoid operator hold times.

Immuno-Oncology and Pfizer

Pfizer is working to advance the science in immuno-oncology and actively exploring a variety of novel agents, including checkpoint modulating antibodies, CAR-T therapies, bi-functional monoclonal antibodies and vaccine-based immunotherapy regimens. Pfizer’s 4-1BB agonist antibody is currently in Phase 1, with several other immunotherapeutic agents expected to commence clinical testing in 2015, including a monoclonal antibody against receptor OX40 (CD134), a PD-1 monoclonal antibody, and a vaccine-based regimen for prostate cancer. Pfizer is exploring the full potential of combining immunotherapies with its broad oncology portfolio through the company’s own development efforts as well as in collaboration with other partners, working together to improve outcomes for patients with cancer.

About XALKORI® (crizotinib)

XALKORI is a kinase inhibitor indicated in the U.S. for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. The U.S. indication is not limited to any specific line of therapy. In the EU, XALKORI is indicated for the treatment of adults with previously treated ALK-positive advanced NSCLC. XALKORI has received approval in more than 75 countries1 including Australia, Canada, China, Japan, South Korea and the European Union.

XALKORI® Important Safety Information

Hepatotoxicity: Across three main clinical trials fatal hepatotoxicity occurred in 0.2% of patients. Monitor with periodic liver testing. Temporarily suspend, dose reduce, or permanently discontinue XALKORI.

Pneumonitis: Across three main clinical trials interstitial lung disease (ILD)/pneumonitis occurred in 2% of patients. Permanently discontinue in patients with ILD/pneumonitis.

QT Interval Prolongation: Across three main clinical trials QT interval prolongation occurred in 2.7% of patients. Monitor with electrocardiograms and electrolytes in patients who have a history of or predisposition for QTc prolongation, or who are taking medications that prolong QT. Temporarily suspend, dose reduce, or permanently discontinue XALKORI.

Bradycardia: XALKORI can cause bradycardia. Across three main clinical trials 11% of patients experienced a heart rate of less than 50 beats per minute. Monitor heart rate and blood pressure regularly. Temporarily suspend, dose reduce, or permanently discontinue XALKORI.

Embryofetal Toxicity: XALKORI can cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant while receiving XALKORI.

Adverse Reactions: Across three main clinical trials the most common adverse reactions (≥25%) were vision disorders, nausea, diarrhea, vomiting, constipation, edema, elevated transaminases, and fatigue.

In a phase 3 study in patients with ALK-positive metastatic NSCLC randomized to XALKORI (n=172) or chemotherapy (n=171), serious adverse reactions were reported in 37.2% of patients treated with XALKORI. The most frequent serious adverse reactions reported in patients treated with XALKORI were pneumonia (4.1%), pulmonary embolism (3.5%), dyspnea (2.3%), and ILD (2.9%). Fatal adverse reactions in XALKORI-treated patients occurred in 9 (5%) patients, consisting of: acute respiratory distress syndrome, arrhythmia, dyspnea, ILD, pneumonia, pneumonitis, pulmonary embolism, respiratory failure, and sepsis. Grade 3 or 4 events occurring at a higher incidence with XALKORI than with chemotherapy and at greater than 2%, were syncope (3%), QT prolongation (3%), and pulmonary embolism (5%). Elevation of ALT of any grade occurred in 76% of patients and grade 3 or 4 in 17% of patients. Neutropenia of any grade occurred in 49% of patients and grade 3 or 4 in 12% of patients. Lymphopenia of any grade occurred in 51% of patients and grade 3 or 4 in 9% of patients. Renal cysts occurred in 4% and neuropathy occurred in 19% of patients treated with XALKORI.

Drug Interactions: Exercise caution with concomitant use of moderate CYP3A inhibitors. Avoid grapefruit or grapefruit juice which may increase plasma concentrations of crizotinib. Avoid concomitant use of strong CYP3A inducers and inhibitors. Dose reduction may be needed for co-administered drugs that are predominantly metabolized by CYP3A.

Nursing Mothers: Given the potential for serious adverse reactions in nursing infants, consider whether to discontinue nursing or discontinue XALKORI.

Hepatic Impairment: XALKORI has not been studied in patients with hepatic impairment. As crizotinib is extensively metabolized in the liver, hepatic impairment is likely to increase plasma crizotinib concentrations. Use caution in patients with hepatic impairment.

Renal Impairment: Administer XALKORI at a starting dose of 250 mg taken orally once daily in patients with severe renal impairment (CLcr<30 mL/min) not requiring dialysis. No starting dose adjustment is needed for patients with mild and moderate renal impairment.

For more information and full prescribing information, please visit www.XALKORI.com.

Pfizer Inc.: Working together for a healthier world®

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of healthcare products. Our global portfolio includes medicines and vaccines as well as many of the world's best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us. To learn more, please visit us at www.pfizer.com

DISCLOSURE NOTICE: The information contained in this release is as of November 17, 2014. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.

This release contains forward-looking information about an agreement between Pfizer and Merck KGaA regarding an immuno-oncology alliance involving anti-PD-L1 and anti-PD-1 therapies and Pfizer’s updated financial guidance for 2014 that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Forward-looking statements include, among other things, those regarding MSB0010718C and the agreement to jointly develop and commercialize MSB0010718C, including plans to explore MSB0010718C as a single agent as well as in various combinations with Pfizer’s and Merck KGaA’s oncology portfolios, plans to advance Pfizer’s anti-PD-1 antibody into Phase 1 clinical trials, development plans for additional clinical trials and plans to jointly commercialize Xalkori in certain markets, and those regarding Pfizer’s immuno-oncology portfolio, including their potential benefits, as well as statements regarding the timing of potential commencement of clinical development programs and testing and regarding Pfizer’s updated financial guidance for 2014 and the expected impact of the exchange of future profits of Xalkori. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical study commencement and completion dates as well as the possibility of unfavorable study results; risks associated with interim data, including the risk that the final results of the Phase 1 study for MSB0010718C and/or additional clinical trials may be different from (including less favorable than) the interim data results and may not support further clinical development; the risk that clinical trial data are subject to differing interpretations, and, even when we view data as sufficient to support the safety and/or effectiveness of a product candidate, regulatory authorities may not share our views and may require additional data or may deny approval altogether; whether and when drug applications may be filed in any jurisdictions for any potential product candidates or combination therapies; whether and when any such applications may be approved by regulatory authorities, which will depend on the assessment by such regulatory authorities of the benefit-risk profile suggested by the totality of the efficacy and safety information submitted; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of any of such product candidates or combination therapies; competitive developments; and regarding Pfizer’s updated financial guidance for 2014, the uncertainties and variables inherent in business, financial and operating performance, including among other things, general economic, political, business, industry, regulatory and market conditions.

A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2013 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the SEC and available at www.sec.gov and www.pfizer.com.

(*) “Reported Diluted EPS” is defined as reported diluted EPS attributable to Pfizer Inc. common shareholders in accordance with U.S. GAAP.

(**)

• Except for the Merck KGaA transaction referenced in this press release, does not assume the completion of any business development transactions not completed as of September 28, 2014 including any one-time upfront payments associated with such transactions.

• Excludes the potential effects of the resolution of litigation-related matters not substantially resolved as of September 28, 2014.
• Exchange rates assumed are a blend of the actual exchange rates in effect through September 28, 2014 and the mid-October 2014 exchange rates for the remainder of the year. Does not include the impact of a potential devaluation of the Venezuelan bolivar or any other currency.

• Guidance for the effective tax rate on adjusted income does not assume renewal of the U.S. research and development (R&D) tax credit. The renewal of the R&D tax credit is not anticipated to have a material impact on the effective tax rate on adjusted income.

• Assumes diluted weighted-average shares outstanding of approximately 6.4 billion shares.

• Revenues and cost of sales from the transitional manufacturing and supply agreements with Zoetis have been excluded from the applicable Adjusted components of the financial guidance.

1 Pfizer data on file.