On January 25, 2019 Oragenics, Inc. (NYSE American:OGEN), a leader in the development of new antibiotics against infectious diseases and effective treatments for oral mucositis ("OM"), reported that Alan Joslyn, Ph.D., president and CEO of Oragenics will be a featured presenter at NobleCon15 – Noble Capital Markets’ Fifteenth Annual Investor Conference on January 28th at 10:30 AM Eastern Standard Time (Press release, Oragenics, JAN 25, 2019, View Source [SID1234532908]). The conference is being held at the W Hotel, Fort Lauderdale, Florida. Dr. Joslyn will provide an overview of the company’s business model and growth strategy and will be available for one-on-one meetings.

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A high-definition, video webcast of the presentation will be available the following day on Oragenics’ web site View Source, and as part of a complete catalog of presentations available at Noble Capital Markets’ websites: www.noblecapitalmarkets.com, and www.nobleconference.com. The webcast and presentation will be archived on the company’s website and on the Noble websites for 90 days following the event.

On January 25, 2019 AbbVie (NYSE:ABBV) reported financial results for the fourth quarter and full year ended December 31, 2018 (Press release, AbbVie, JAN 25, 2019, View Source [SID1234532894]).

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"We delivered exceptional performance in 2018, including operational revenue growth of more than 15 percent and EPS growth above 40 percent," said Richard A. Gonzalez, chairman and chief executive officer, AbbVie. "We’re entering an important new phase for AbbVie. The continued momentum of our business, combined with the launch and ramp of several new products, will allow us to drive strong earnings growth once again in 2019 and position us for growth over the longer term."

Fourth-Quarter Results

Worldwide GAAP net revenues were $8.305 billion in the fourth quarter, up 7.3 percent year-over-year. Worldwide adjusted net revenues of $8.305 billion increased 8.3 percent on an operational basis, excluding a 1.0 percent unfavorable impact from foreign exchange.
Global HUMIRA sales increased 0.5 percent on a reported basis, or 1.4 percent operationally, excluding a 0.9 percent unfavorable impact from foreign exchange. In the U.S., HUMIRA sales grew 9.1 percent in the quarter. Internationally, HUMIRA sales declined 14.8 percent operationally due to direct biosimilar competition in certain international markets.
Global net revenues from the hematologic oncology portfolio were $1.130 billion, an increase of 50.2 percent on a reported basis; global IMBRUVICA net revenues were $1.006 billion, an increase of 42.0 percent; global VENCLEXTA net revenues were $124 million.
Fourth-quarter global HCV net revenues were $862 million.
On a GAAP basis, the gross margin ratio in the fourth quarter was 75.7 percent. The adjusted gross margin ratio was 79.8 percent.
On a GAAP basis, selling, general and administrative expense was 23.2 percent of net revenues. The adjusted SG&A expense was 21.6 percent of net revenues.
On a GAAP basis, research and development expense was 78.2 percent of net revenues. The adjusted R&D expense was 16.5 percent, reflecting funding actions supporting all stages of our pipeline.
On a GAAP basis, the operating margin in the fourth quarter was negative 29.4 percent. The adjusted operating margin was 41.7 percent.
On a GAAP basis, net interest expense was $319 million. On a GAAP basis, the tax rate in the quarter was 23.1 percent. The adjusted tax rate was 9.1 percent.
Diluted loss per share in the fourth quarter was $1.23 on a GAAP basis, inclusive of the recent partial impairment charge related to intangible assets acquired as part of the 2016 acquisition of Stemcentrx, Inc. Adjusted diluted EPS, excluding specified items, was $1.90, up 28.4 percent.
Key Events from the Fourth Quarter

AbbVie announced the U.S. Food and Drug Administration (FDA) granted accelerated approval to VENCLEXTA (venetoclax) in combination with azacitidine, or decitabine, or low-dose cytrabine (LDAC) for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials, which are expected to be completed in 2019. The approval in AML is the third provided under priority review by the FDA for VENCLEXTA, which has been granted four Breakthrough Therapy Designations (BTDs) by the FDA. Venetoclax is being developed by AbbVie and Roche and is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.
AbbVie announced the European Commission (EC) has approved the type-II variation application for VENCLYXTO (venetoclax) in combination with rituximab for the treatment of patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. This approval allows more patients to receive VENCLYXTO in combination with rituximab in the second-line setting. It also gives healthcare providers the ability to prescribe this medicine to a broader population of patients with R/R CLL than the previously approved indication for VENCLYXTO as monotherapy in the European Union. The approval is based on results from the Phase 3 MURANO trial, which demonstrated a statistically significant improvement in investigator-assessed progression-free survival (PFS) for patients who received VENCLYXTO plus rituximab compared with bendamustine plus rituximab.
At the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (ASH) (Free ASH Whitepaper), AbbVie presented data from nearly 40 abstracts, including 13 oral presentations and more than 20 poster presentations. Multiple studies investigating VENCLEXTA and IMBRUVICA (ibrutinib) across a number of hematologic malignancies were presented, including updated results from the Phase 3 MURANO trial of venetoclax in combination with rituximab in patients with R/R CLL, which showed that treatment with VENCLEXTA and rituximab provided sustained benefits in PFS and minimal residual following an additional year of follow-up data.
AbbVie and its collaboration partners presented new and updated IMBRUVICA data at the ASH (Free ASH Whitepaper) meeting, including results from three Phase 3 studies in patients with previously untreated CLL. In the Phase 3 iLLUMINATE trial, IMBRUVICA plus obinutuzumab significantly prolonged PFS with a 77 percent reduction in risk of progression or death versus chlorambucil plus obinutuzumab. In the Phase 3 ECOG-1912 trial, IMBRUVICA plus rituximab significantly prolonged PFS and improved overall survival (OS) compared to fludarabine, cyclophosphamide and rituximab (FCR) in previously untreated younger patients with CLL. And in the Phase 3 ALLIANCE trial, IMBRUVICA alone or in combination with rituximab produced superior PFS compared with bendamustine plus rituximab (BR) in untreated older patients with CLL. Also featured at ASH (Free ASH Whitepaper) were seven-year data on patients treated with IMBRUVICA, which showed durable responses and sustained PFS rates with IMBRUVICA in CLL/SLL (small lymphocytic lymphoma) for previously untreated patients.
AbbVie announced topline results on the Phase 3 RESOLVE trial (PCYC-1137) of IMBRUVICA in combination with nab-paclitaxel and gemcitabine versus placebo in combination with these chemotherapy agents in patients with metastatic pancreatic adenocarcinoma (cancer). At conclusion, the study did not meet its primary endpoint of improving PFS or OS benefit among the study population. Full results from this study will be submitted for presentation at a future medical meeting.
Following the decision to stop enrollment for the TAHOE trial, a Phase 3 study evaluating Rovalpituzumab Tesirine (Rova-T) as a second-line therapy for advanced small-cell lung cancer (SCLC), and an evaluation of the Stemcentrx-related intangible assets, AbbVie recorded an impairment charge related to intangible assets acquired as part of its 2016 acquisition of Stemcentrx, Inc. The after-tax net impact of this impairment and the related adjustment to contingent consideration liabilities was $4.117 billion. AbbVie continues to evaluate information with respect to the Stemcentrx-related clinical development programs and will monitor the remaining $1 billion of intangible assets for further impairment.
AbbVie announced that it submitted a New Drug Application (NDA) to the FDA and a marketing authorization application (MAA) to the European Medicines Agency for upadacitinib, an oral investigational JAK1-selective inhibitor, for the treatment of adult patients with moderate to severe rheumatoid arthritis. The NDA and MAA are supported by data from the global upadacitinib SELECT Phase 3 rheumatoid arthritis program evaluating more than 4,900 patients with moderate to severe rheumatoid arthritis across five Phase 3 studies. In the SELECT program, results showed that upadacitinib improved signs and symptoms of rheumatoid arthritis, inhibited radiographic progression and improved physical function, both as a monotherapy and in combination with conventional synthetic DMARDs.
At the American College of Rheumatology (ACR)/Association for Rheumatology Health Professionals (ARHP) Annual Meeting, AbbVie presented new data for upadacitinib and HUMIRA, with 35 abstracts presented across multiple rheumatic conditions, including rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis and uveitis. Included in the presentations were data from three of the five pivotal studies from the SELECT Phase 3 program.
At the United European Gastroenterology Week (UEGW) conference, AbbVie showcased its gastroenterology portfolio with 11 presentations of HUMIRA and pipeline data, including the first presentation of data from a Phase 2b study (U-ACHIEVE) evaluating upadacitinib in adult patients with moderately to severely active ulcerative colitis. Results from the U-ACHIEVE study demonstrated that after 8 weeks, upadacitinib (15/30/45 mg, once daily) met the primary endpoint of clinical remission (per adapted Mayo Score) and ranked secondary endpoints, including endoscopic improvement, clinical remission (per Full Mayo Score) and clinical response.
At the American Association of Gynecologic Laparoscopists (AAGL) Global Congress on Minimally Invasive Gynecology, AbbVie, in cooperation with Neurocrine Biosciences, presented additional results from two replicate pivotal Phase 3 clinical trials ELARIS UF-1 and ELARIS UF-2 evaluating the efficacy and safety of elagolix in women with uterine fibroids. Results demonstrated that at the final month of the six-month treatment period, elagolix, in combination with low-dose hormone (add-back) therapy, reduced heavy menstrual bleeding associated with uterine fibroids compared to placebo. Data from the Phase 3 clinical trial program will support regulatory submission for elagolix in uterine fibroids, anticipated in mid-2019.
At the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), AbbVie presented new data for its pan-genotypic chronic hepatitis C virus (HCV) treatment, MAVYRET (glecaprevir/pibrentasvir), in treatment-naïve patients with compensated cirrhosis. Results from the Phase 3b EXPEDITION-8 study showed that with 8 weeks of MAVYRET, 100 percent of genotype 1, 2, 4, 5 and 6 patients achieved a sustained virologic response 12 weeks after treatment per protocol analysis. MAVYRET is currently approved as an 8-week, pan-genotypic treatment for treatment-naïve patients without cirrhosis.
AbbVie announced global resolutions of all intellectual property-related litigation with Momenta and Pfizer over their proposed biosimilar adalimumab products. Under the terms of the settlement agreements, AbbVie will grant to Momenta and Pfizer non-exclusive licenses to AbbVie’s intellectual property relating to HUMIRA beginning on certain dates in certain countries in which AbbVie has intellectual property. The license period will begin on November 20, 2023 in the U.S. for both Momenta and Pfizer, and will not be accelerated by the entry of companies who have already taken a license. Momenta and Pfizer will pay royalties to AbbVie for licensing its HUMIRA patents and both manufacturers acknowledge the validity of the licensed patents. AbbVie will make no payments to Momenta or Pfizer. AbbVie has entered into a total of seven settlement agreements with manufacturers related to the licensing of proposed biosimilar adalimumab products.
AbbVie announced its board of directors authorized a $5 billion increase to the company’s existing stock repurchase program. Purchases may be made from time to time at management’s discretion. The stock repurchase authorization permits shares to be repurchased in open market or private transactions, has no time limit and may be discontinued at any time.
AbbVie made charitable contributions totaling $115 million in the fourth quarter, including a $50 million donation to St. Jude Children’s Research Hospital to enhance and expand patient and family-centered care. In 2018, AbbVie made a total of $350 million in charitable contributions to U.S. non-for-profit organizations. The contributions provide AbbVie with the opportunity to support charities creating long-term impact in communities in need, including Puerto Rico, North Chicago and cities across America.
Full-Year 2019 Outlook

AbbVie is issuing GAAP diluted EPS guidance for the full-year 2019 of $7.39 to $7.49. The company’s 2019 GAAP guidance does not reflect non-cash charges for contingent consideration adjustments related to the expected approval of risankizumab in the first half of the year. AbbVie expects to deliver adjusted diluted EPS for the full-year 2019 of $8.65 to $8.75, representing growth of 10.0 percent at the mid-point. The company’s 2019 adjusted diluted EPS guidance excludes $1.26 per share of intangible asset amortization expense, non-cash charges for contingent consideration adjustments, and other specified items.

On January 24, 2019 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that the European Commission (EC) has approved the use of Rubraca (rucaparib) for a second indication, as monotherapy for the maintenance treatment of adults with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy (Press release, Clovis Oncology, JAN 24, 2019, View Source [SID1234532895]). This expands rucaparib’s indication beyond its initial marketing authorization in Europe granted in May 2018 and with this label expansion, rucaparib is now available to patients regardless of their BRCA mutation status. Rucaparib was the first PARP inhibitor licensed for an ovarian cancer treatment indication in the EU and is now the first to be available for both treatment and maintenance treatment among eligible patients.

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The EC authorization is based on data from the phase 3 ARIEL3 clinical trial, which found that rucaparib significantly improved progression-free survival in all ovarian cancer patient populations studied.i

For the full European approved prescribing information, please refer to the Rubraca (rucaparib) Summary of Product Characteristics on the European Medicines Agency website.

Ovarian cancer is the sixth deadliest cancer among women in Europe, where more than 65,000 women are diagnosed annually.ii Moreover, the 80 to 85 percent of women diagnosed in the later stages of the disease (III and IV) have particularly poor outcomes.iii Ovarian cancer is challenging to treat, and most women will relapse after surgery and chemotherapy. Multiple studies, including the rucaparib ARIEL3 clinical trial, have demonstrated that maintenance treatment with a PARP inhibitor significantly extends median progression free survival (mPFS) as compared to observation (i.e., "watch and wait" or placebo).i

"This EC authorization of rucaparib is an important step in ensuring that it is available to all women who may potentially benefit, regardless of their BRCA status," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We believe that access to maintenance treatment is extremely important for women with relapsed platinum-sensitive ovarian cancer, and we are pleased that rucaparib can now be an option for these women. As the only PARP inhibitor that has shown further tumor shrinkage as well as prolonged progression-free survival in this maintenance setting, we believe Rubraca represents an important step forward for women with advanced ovarian cancer."

The ARIEL3 trial was a double-blind, placebo-controlled clinical trial of rucaparib that enrolled 564 women with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer in complete or partial response to platinum-based chemotherapy. Patients were randomized (2:1) to receive rucaparib tablets 600mg twice daily (n=375) or placebo (n=189).

ARIEL3 successfully achieved its primary endpoint, of extending investigator-assessed progression-free survival (PFS) versus placebo in all patients treated (intention-to-treat [ITT]), population, regardless of BRCA status; the key secondary endpoint of extending PFS as assessed by independent radiological review (IRR) was also achieved.

Parameter Investigator assessment IRR
Rucaparib Placebo Rucaparib Placebo
All patients
Patients, n 375 189 375 189
PFS events, n (%) 234 (62) 167 (88) 165 (44) 133 (70)
PFS, median in months (95% CI) 10.8 (8.3, 11.4) 5.4 (5.3, 5.5) 13.7 (11.0, 19.1) 5.4 (5.1, 5.5)
HR (95% CI) 0.36 (0.30, 0.45) 0.35 (0.28, 0.45)
p-value <0.0001 <0.0001
tBRCA Group
Patients, n 130 66 130 66
PFS events, n (%) 67 (52) 56 (85) 42 (32) 42 (64)
PFS, median in months (95% CI) 16.6 (13.4, 22.9) 5.4 (3.4, 6.7) 26.8 (19.2, NA) 5.4 (4.9, 8.1)
HR (95% CI) 0.23 (0.16, 0.34) 0.20 (0.13, 0.32)
p-value <0.0001 <0.0001

An exploratory analysis of patients in the ITT population with measurable disease at baseline showed a tumor response was reported in 18% (95% CI 12%–26%) of patients (n=26) on rucaparib compared to 8% (95% CI 3% – 17%) of patients (n=5) on placebo (p value = 0.0069), including 10 patients (7%) in the rucaparib group who achieved a complete remission.

The overall safety profile of rucaparib is based on data from 937 patients with ovarian cancer treated with rucaparib monotherapy in clinical trials. Adverse reactions occurring in ≥20% of patients were nausea, fatigue/asthenia, vomiting, anaemia, abdominal pain, dysgeusia, alanine aminotransferase (ALT) elevations, aspartate aminotransferase (AST) elevations, decreased appetite, diarrhoea, thrombocytopenia and creatinine elevations. The majority of adverse reactions were mild to moderate (Grade 1 or 2).

Grade ≥3 adverse reactions occurring in >5% of patients were anemia (23%), ALT elevations (10%), fatigue/asthenia (10%), neutropenia (8%), thrombocytopenia (6%), and nausea (5%). The only serious adverse reaction occurring in > 2% of patients was anemia (5%).

Adverse reactions that most commonly led to dose reduction or interruption were anemia (20%), fatigue/asthenia (18%), nausea (16%), thrombocytopenia (15%), and AST/ALT elevations (10%). Adverse reactions leading to permanent discontinuation occurred in 10% of patients, with thrombocytopenia, nausea, anaemia, and fatigue/asthenia being the most frequent adverse reactions leading to permanent discontinuation.

About Rubraca (rucaparib)

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian, metastatic castration-resistant prostate, and bladder cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Clovis holds worldwide rights for Rubraca. Rubraca is an unlicensed medical product outside of the U.S. and Europe.

Rubraca (rucaparib) EU Authorized Use and Important Safety Information

Rucaparib is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

Rucaparib is indicated as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Summary warnings and precautions: Haematological toxicity: Patients should not start Rubraca until they have recovered from haematological toxicities caused by previous chemotherapy (≤ CTCAE Grade 1). Complete blood count testing prior to starting treatment with Rubraca and monthly thereafter is advised. Rubraca should be interrupted or dose reduced and blood counts monitored weekly until recovery for the management of low blood counts. Myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML): If MDS/AML is suspected, the patient should be referred to a haematologist for further investigation. If MDS/AML is confirmed, Rubraca should be discontinued. Photosensitivity: Patients should avoid spending time in direct sunlight as they may burn more easily. When outdoors, patients should wear protective clothing and sunscreen with SPF of 50 or greater. Gastrointestinal toxicities: Low grade (CTCAE Grade 1 or 2) nausea and vomiting may be managed with dose reduction or interruption. Additionally, antiemetics may be considered for treatment or prophylaxis.

Click here to access the current Summary of Product Characteristics. Healthcare professionals should report any suspected adverse reactions via their national reporting systems.

On January 24, 2019 Bristol-Myers Squibb Company (NYSE:BMY) reported that its fourth quarter 2018 earnings call has been rescheduled for two hours earlier than previously announced (Press release, Bristol-Myers Squibb, JAN 24, 2019, View Source [SID1234532879]). The new time for the call is 8:30 a.m. ET today. The dial-in information remains the same and is listed below. During the conference call, company executives will review financial information and will address inquiries from investors and analysts.

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Investors and the general public are invited to listen to a live webcast of the call at View Source or by dialing in the U.S. toll free 800-458-4121 or international 786-789-4772, confirmation code: 9368504. Materials related to the call will be available at the same website prior to the conference call. A replay of the call will be available beginning at 11:45 a.m. ET on January 24 through 11:45 a.m. ET on February 7, 2019. The replay will also be available through View Source or by dialing in the U.S. toll free 888-203-1112 or international 719-457-0820, confirmation code: 9368504.

On January 24, 2019 Bristol-Myers Squibb Company (NYSE:BMY) reported results for the fourth quarter and full year of 2018 which were highlighted by strong demand for Opdivo (nivolumab) and Eliquis (apixaban) and a robust operating performance across the portfolio (Press release, Bristol-Myers Squibb, JAN 24, 2019, View Source [SID1234532880]).

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"I am proud of our results in 2018, which were based on superior commercial performance for our prioritized brands and important scientific advances that continue to diversify our R&D pipeline. We are beginning 2019 with good momentum in our current business, with Opdivo and Eliquis continuing as strong and growing franchises," said Giovanni Caforio, M.D., chairman and chief executive officer, Bristol-Myers Squibb. "Our planned acquisition of Celgene will position us to create a leading biopharma company, with best-in-class franchises, significant near-term launch opportunities and a deep and broad pipeline, creating an even stronger foundation for long-term sustainable growth."

Fourth Quarter

$ amounts in millions, except per share amounts
2018

2017

Change

Total Revenues $5,973 $5,449 10%
GAAP Diluted EPS 0.73 (1.42) **
Non-GAAP Diluted EPS 0.94 0.68 38%

Full Year

$ amounts in millions, except per share amounts
2018

2017

Change

Total Revenues $22,561 $20,776 9%
GAAP Diluted EPS 3.03 0.61 **
Non-GAAP Diluted EPS 3.98 3.01 32%

**In excess of +/- 100%

FOURTH QUARTER FINANCIAL RESULTS

Bristol-Myers Squibb posted fourth quarter 2018 revenues of $6.0 billion, an increase of 10% compared to the same period a year ago. Revenues increased 12% when adjusted for foreign exchange impact.
U.S. revenues increased 16% to $3.3 billion in the quarter compared to the same period a year ago. International revenues increased 3%. When adjusted for foreign exchange impact, international revenues increased 7%.
Gross margin as a percentage of revenue increased from 69.2% to 71.7% in the quarter primarily due to higher inventory write-offs and startup charges in the fourth quarter last year.
Marketing, selling and administrative expenses increased 2% to $1.3 billion in the quarter.
Research and development expenses decreased 29% to $1.4 billion in the quarter primarily due to license and asset acquisition charges of $377 million in the fourth quarter last year.
The effective tax rate was 23.1% in the quarter, compared to 433.7% in the fourth quarter last year. The tax rate in the fourth quarter last year was impacted by a one-time $2.9 billion charge resulting from U.S. tax reform.
The company reported net earnings attributable to Bristol-Myers Squibb of $1.2 billion, or $0.73 per share, in the fourth quarter, compared to a net loss of $2.3 billion, or $1.42 per share, for the same period in 2017. The results in the fourth quarter last year included the transitional impact of U.S. tax reform.
The company reported non-GAAP net earnings attributable to Bristol-Myers Squibb of $1.5 billion, or $0.94 per share, in the fourth quarter, compared to net earnings of $1.1 billion, or $0.68 per share, for the same period in 2017. An overview of specified items is discussed under the "Use of Non-GAAP Financial Information" section.
Cash, cash equivalents and marketable securities were $10.7 billion, with a net cash position of $3.3 billion, as of December 31, 2018.
ACQUISITION OF CELGENE CORPORATION

In January, the company and Celgene Corporation announced they have entered into a definitive merger agreement under which the company will acquire Celgene. (link)
FOURTH QUARTER PRODUCT AND PIPELINE UPDATE

Product Sales/Business Highlights

Global revenues for the fourth quarter of 2018, compared to the fourth quarter of 2017, were driven by:

Opdivo , which grew by $443 million or a 33% increase
Eliquis , which grew by $342 million or a 25% increase
Yervoy , which grew by $115 million or a 43% increase
Orencia , which grew by 10%
Sprycel , which grew by 2%
Opdivo

Regulatory

Following recent discussions with the U.S. Food and Drug Administration (FDA), the company reported the voluntary withdrawal of the U.S. supplemental Biologics License Application (sBLA) for the Opdivo and low-dose Yervoy (ipilimumab) combination for treatment of first-line advanced non-small cell lung cancer (NSCLC) in patients with tumor mutational burden (TMB) ≥10 mutations/megabase (mut/Mb).

In October 2018, the company announced the submission of an exploratory overall survival (OS) analysis for the TMB <10 mut/Mb subgroup to the FDA. The FDA determined at that time, that the submission of this new information constituted a major amendment to the sBLA and extended the review period by three months, moving the Prescription Drug User Fee Act date to May 20, 2019.

After recent discussions with the FDA, the company believes further evidence on the relationship between TMB and PD-L1 is required to fully evaluate the impact of Opdivo plus Yervoy on OS in first-line NSCLC patients. This analysis will require availability of the final data from Checkmate -227, Part 1a (Opdivo plus low-dose Yervoy or Opdivo monotherapy versus chemotherapy in patients whose tumors express PD-L1), which the company anticipates will be available in the first-half of 2019. Since these data from Checkmate -227, Part 1a, will not be available within the review cycle of the current application the company decided to withdraw.
In January, the company announced the European Commission approved the combination of Opdivo plus Yervoy for the first-line treatment of patients with intermediate- and poor-risk advanced renal cell carcinoma.
Clinical

In November, the company announced top-line results from the Phase 3 CheckMate -451 trial in patients with extensive-stage small cell lung cancer without disease progression after completion of first-line platinum-based chemotherapy treatment with Opdivo plus Yervoy versus placebo. (link)
Eliquis

Clinical

In November, at the American Heart Association Scientific Sessions 2018, the company-Pfizer alliance presented new real-world evidence from a sub-analysis of the ARISTOPHANES study comparing the safety and effectiveness of non-vitamin K antagonist oral anticoagulants, including Eliquis, in non-valvular atrial fibrillation patient populations aged 80 and older. (link)
Sprycel

Regulatory

In January, the company announced the U.S. Food and Drug Administration (FDA) expanded the indication for Sprycel (dasatinib) tablets to include the treatment of pediatric patients one year of age or older with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in combination with chemotherapy.
In December, the company announced the Committee for Medicinal Products for Human Use of the European Medicines Agency recommended the expanded approval of Sprycel, in combination with chemotherapy, to include the treatment of pediatric patients with newly diagnosed Ph+ ALL.
Empliciti

Regulatory

In November, the company announced the FDA approved Empliciti (elotuzumab) in combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
FOURTH QUARTER BUSINESS DEVELOPMENT UPDATE

In December, the company announced Taisho Pharmaceutical Holdings Co., Ltd. offered to purchase the company’s UPSA consumer health business for $1.6 billion.
In December, the company and Boston Medical Center announced a multi-year joint research study to identify and analyze potential sensitivity and resistance markers in patients treated with standard-of-care checkpoint inhibitors.
In December, the company, Eisai Co., Ltd. and its U.S.-based precision medicine research & development subsidiary H3 Biomedicine, Inc. announced a multi-year research collaboration to explore modulating RNA splicing to develop potential first-in-class therapies that would direct the immune system to target cancer cells and help more patients experience the benefits of immunotherapy.
In December, the company and Vedanta Biosciences announced a clinical trial collaboration to evaluate Opdivo in combination with Vedanta Biosciences’ VE800 in patients with advanced or metastatic cancers.
In November, the company and Infinity Pharmaceuticals, Inc. announced a clinical trial collaboration to evaluate Opdivo in combination with Infinity’s IPI-549 in patients with advanced urothelial cancer.
2019 FINANCIAL GUIDANCE

Bristol-Myers Squibb is confirming its 2019 GAAP EPS guidance range of $3.75 – $3.85 and its non-GAAP EPS guidance range of $4.10 – $4.20. Both GAAP and non-GAAP guidance assume current exchange rates. Key 2019 GAAP and non-GAAP line-item guidance assumptions are:

Worldwide revenues increasing in the mid-single digits.
Gross margin as a percentage of revenue to be approximately 70% to 71% for both GAAP and non-GAAP.
Marketing, selling and administrative expenses decreasing in the mid-single digit range for both GAAP and non-GAAP.
Research and development expenses decreasing in the mid-single digits for GAAP and increasing in the high-single digits for non-GAAP.
An effective tax rate of approximately 15% for GAAP and approximately 17% for non-GAAP.
The financial guidance for 2019 excludes the impact of any potential future strategic acquisitions and divestitures, including any impact of the Celgene acquisition, and any specified items that have not yet been identified and quantified. The non-GAAP 2019 guidance also excludes other specified items as discussed under "Use of Non-GAAP Financial Information." Details reconciling adjusted non-GAAP amounts with the amounts reflecting specified items are provided in supplemental materials available on the company’s website.

Use of Non-GAAP Financial Information

This press release contains non-GAAP financial measures, including non-GAAP earnings and related EPS information, that are adjusted to exclude certain costs, expenses, gains and losses and other specified items that are evaluated on an individual basis. These items are adjusted after considering their quantitative and qualitative aspects and typically have one or more of the following characteristics, such as being highly variable, difficult to project, unusual in nature, significant to the results of a particular period or not indicative of future operating results. Similar charges or gains were recognized in prior periods and will likely reoccur in future periods, including restructuring costs, accelerated depreciation and impairment of property, plant and equipment and intangible assets, R&D charges in connection with the acquisition or licensing of third party intellectual property rights, divestiture and equity investment gains or losses, upfront payments from out-licensed assets, pension charges, legal and other contractual settlements and debt redemption gains or losses, among other items. Deferred and current income taxes attributed to these items are also adjusted for considering their individual impact to the overall tax expense, deductibility and jurisdictional tax rates. Non-GAAP information is intended to portray the results of our baseline performance, supplement or enhance management, analysts and investors overall understanding of our underlying financial performance and facilitate comparisons among current, past and future periods. For example, non-GAAP earnings and EPS information is an indication of our baseline performance before items that are considered by us to not be reflective of our ongoing results. In addition, this information is among the primary indicators that we use as a basis for evaluating performance, allocating resources, setting incentive compensation targets and planning and forecasting for future periods. This information is not intended to be considered in isolation or as a substitute for net earnings or diluted EPS prepared in accordance with GAAP and may not be the same as or comparable to similarly titled measures presented by other companies due to possible differences in method and in the items being adjusted.

Company and Conference Call Information

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 about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.

There will be a conference call on January 24, 2019 at 8:30 a.m. ET during which company executives will review financial information and address inquiries from investors and analysts. Investors and the general public are invited to listen to a live webcast of the call at View Source or by calling the U.S. toll free 800-458-4121 or international 786-789-4772, confirmation code: 9368504. Materials related to the call will be available at the same website prior to the conference call. A replay of the call will be available beginning at 11:45 a.m. ET on January 24, 2019 through 11:45 a.m. ET on February 7, 2019. The replay will also be available through View Source or by calling the U.S. toll free 888-203-1112 or international 719-457-0820, confirmation code: 9368504.

Website Information

We routinely post important information for investors on our website, BMS.com, in the "Investors" section. We may use this website as a means of disclosing material, non-public information and for complying with our disclosure obligations under Regulation FD. Accordingly, investors should monitor the Investors section of our website, in addition to following our press releases, SEC filings, public conference calls, presentations and webcasts. We may also use social media channels to communicate with our investors and the public about our company, our products and other matters, and those communications could be deemed to be material information. The information contained on, or that may be accessed through, our website or social media channels are not incorporated by reference into, and are not a part of, this document.

Important Information for Investors and Stockholders

This communication does not constitute an offer to sell or the solicitation of an offer to buy any securities or a solicitation of any vote or approval. It does not constitute a prospectus or prospectus equivalent document. No offering of securities shall be made except by means of a prospectus meeting the requirements of Section 10 of the U.S. Securities Act of 1933, as amended.

In connection with the proposed transaction between Bristol-Myers Squibb Company ("Bristol-Myers Squibb") and Celgene Corporation ("Celgene"), Bristol-Myers Squibb and Celgene will file relevant materials with the Securities and Exchange Commission (the "SEC"), including a Bristol-Myers Squibb registration statement on Form S-4 that will include a joint proxy statement of Bristol-Myers Squibb and Celgene that also constitutes a prospectus of Bristol-Myers Squibb, and a definitive joint proxy statement/prospectus will be mailed to stockholders of Bristol-Myers Squibb and Celgene. INVESTORS AND SECURITY HOLDERS OF BRISTOL-MYERS SQUIBB AND CELGENE ARE URGED TO READ THE JOINT PROXY STATEMENT/PROSPECTUS AND OTHER DOCUMENTS THAT WILL BE FILED WITH THE SEC CAREFULLY AND IN THEIR ENTIRETY WHEN THEY BECOME AVAILABLE BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION. Investors and security holders will be able to obtain free copies of the registration statement and the joint proxy statement/prospectus (when available) and other documents filed with the SEC by Bristol-Myers Squibb or Celgene through the website maintained by the SEC at View Source." target="_blank" title="View Source." rel="nofollow">View Source Copies of the documents filed with the SEC by Bristol-Myers Squibb will be available free of charge on Bristol-Myers Squibb’s internet website at View Source under the tab, "Investors" and under the heading "Financial Reporting" and subheading "SEC Filings" or by contacting Bristol-Myers Squibb’s Investor Relations Department through View Source Copies of the documents filed with the SEC by Celgene will be available free of charge on Celgene’s internet website at View Source under the tab "Investors" and under the heading "Financial Information" and subheading "SEC Filings" or by contacting Celgene’s Investor Relations Department at [email protected].

Certain Information Regarding Participants

Bristol-Myers Squibb, Celgene, and their respective directors and executive officers may be considered participants in the solicitation of proxies in connection with the proposed acquisition of Celgene. Information about the directors and executive officers of Bristol-Myers Squibb is set forth in its Annual Report on Form 10-K for the year ended December 31, 2017, which was filed with the SEC on February 13, 2018, its proxy statement for its 2018 annual meeting of stockholders, which was filed with the SEC on March 22, 2018, and its Current Report on Form 8-K, which was filed with the SEC on August 28, 2018. Information about the directors and executive officers of Celgene is set forth in its Annual Report on Form 10-K for the year ended December 31, 2017, which was filed with the SEC on February 7, 2018, its proxy statement for its 2018 annual meeting of stockholders, which was filed with the SEC on April 30, 2018, and its Current Reports on Form 8-K, which were filed with the SEC on June 1, 2018, June 19, 2018 and November 2, 2018. Other information regarding the participants in the proxy solicitations and a description of their direct and indirect interests, by security holdings or otherwise, will be contained in the joint proxy statement/prospectus and other relevant materials to be filed with the SEC regarding the proposed transaction when they become available. You may obtain these documents (when they become available) free of charge through the website maintained by the SEC at View Source and from Investor Relations at Bristol-Myers Squibb or Celgene as described above.