On April 25, 2017 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapies, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to tazemetostat, the Company’s first-in-class EZH2 inhibitor, for the treatment of patients with relapsed or refractory follicular lymphoma, either wild type EZH2 or with EZH2 activating mutations (Press release, Epizyme, APR 25, 2017, View Source [SID1234518681]). Fast Track designation is intended to provide expedited processes for the development and FDA review of drugs that may reduce development time and costs associated with bringing a drug to market.

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Epizyme also announced that interim efficacy and safety data from all five study cohorts in its ongoing Phase 2 study of tazemetostat in patients with relapsed or refractory follicular lymphoma and diffuse large B-cell lymphoma (DLBCL) has been selected for a plenary session on Wednesday, June 14, 2017 at 2:00 p.m. CET at the International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland. In addition, results from a biomarker study of tazemetostat in patients with NHL will be presented in a poster session during ICML. The Company plans to hold a conference call to discuss these clinical findings on Wednesday, June 14 at 10:30 a.m. ET.

"This is an important milestone for our NHL program, with tazemetostat now having FDA Fast Track designation for relapsed or refractory diffuse large B-cell lymphoma with EZH2 activating mutations and for relapsed or refractory follicular lymphoma, regardless of EZH2 mutation," said Robert Bazemore, president and chief executive officer, Epizyme. "In addition to this regulatory recognition of tazemetostat’s therapeutic potential, the selection of interim Phase 2 data for the opening plenary session underscores the lymphoma community’s enthusiasm for our lead product candidate. Our development goal is to bring tazemetostat to patients as quickly as possible and we look forward to advancing this study throughout 2017."

The FDA Fast Track program is designed to facilitate the development of important new drugs and to provide patients access to those drugs more quickly. The designation enables early and frequent communication between FDA and a product sponsor throughout the drug development and review process. Through the Fast Track program, a product may be eligible for priority review at the time of a new drug application (NDA) filing and may also be eligible to submit completed sections of the NDA on a rolling basis before the complete application is submitted.

About the Tazemetostat Clinical Trial Program
Tazemetostat, a first-in-class EZH2 inhibitor, is currently being studied in ongoing Phase 2 programs in both follicular lymphoma and diffuse large B-cell lymphoma (DLBCL) forms of non-Hodgkin lymphoma; certain genetically defined solid tumors, including INI1-negative and SMARCA4-negative tumors and synovial sarcoma; and mesothelioma, as well as in combination studies in DLBCL. Tazemetostat has been granted Fast Track designation by the U.S. Food and Drug Administration for both relapsed/refractory follicular lymphoma with or without an EZH2 activating mutation and DLBCL with EZH2 activating mutations, as well as Orphan Drug designation for malignant rhabdoid tumors.

On April 25, 2017 DelMar Pharmaceuticals, Inc. (Nasdaq: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported that it has entered into a three-year collaboration with Duke University to evaluate VAL-083, the Company’s platform compound, as a front-line treatment for newly diagnosed patients with glioblastoma multiforme ("GBM") (Press release, DelMar Pharmaceuticals, APR 25, 2017, View Source [SID1234518680]).

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Under the terms of the collaboration, DelMar will fund a series of pre-clinical studies to be conducted by Duke University’s Glioblastoma Drug Discovery Group to evaluate VAL-083, either alone or in combination with other agents, for activity against a range of glioblastoma subtypes (personalized drug development). The goal of the research will be to identify molecular characteristics of GBM tumors that are more likely to respond to VAL-083, and not the standard of care, temozolomide, as a front-line treatment or through combination therapies.

"VAL-083 is a promising drug that has the potential to help many GBM patients, especially the over half of GBM patients whose tumors predominantly exhibit an unmethylated MGMT promoter and do not respond to temozolomide, the current standard of care," commented Dr. Madan Kwatra, Director of the Glioblastoma Drug Discovery Group at Duke University.

GBM is a deadly brain cancer in which the current standard of care consists of surgery followed by radiation and chemotherapy using temozolomide. However, temozolomide only works for about 40% of GBM patients that have a methylated MGMT promoter. In contrast, VAL-083 is a novel chemotherapeutic agent that has activity against GBM with both methylated and unmethylated MGMT promoters. As such, VAL-083 is a more versatile chemotherapeutic agent that may help a wider subset of GBM patients.

"We are delighted to be working with another top-tier research institute and in particular, Dr. Kwatra who is a world renowned expert in the GBM field," stated Jeffrey Bacha, chairman and chief executive officer of DelMar Pharmaceuticals. "The efforts of his department in the coming years will greatly contribute to our goal of optimizing VAL-083 as a next generation personalized solution for a broad range of cancers."

About VAL-083:

VAL-083 is a "first-in-class," small-molecule chemotherapeutic that demonstrated clinical activity against a range of cancers including GBM in historical clinical trials sponsored by the U.S. National Cancer Institutes. DelMar has demonstrated that VAL-083’s anti-tumor activity against GBM is unaffected by the expression of MGMT in vitro. Further details can be found at View Source

VAL-083 has received an orphan drug designation in Europe for the treatment of malignant gliomas and the U.S. FDA Office of Orphan Products has granted an orphan designation to VAL-083 for the treatment of glioma, medulloblastoma and ovarian cancer.

DelMar is currently conducting a Phase 2 clinical trial in patients with MGMT-unmethylated, Bevacizumab-naive, recurrent GBM in collaboration with the University of Texas MD Anderson Cancer Center. DelMar has also announced plans to advance VAL-083 into a pivotal randomized multi-center Phase 3 clinical trial for the treatment of bevacizumab-failed GBM and into a separate international Phase 2 trial for newly diagnosed MGMT-unmethylated GBM patients.

DelMar believes that data from its clinical trials, if successful, will form the basis of a new treatment paradigm for the vast majority of GBM patients whose tumors exhibit features that make them unlikely to respond to currently available therapies.

About Glioblastoma Multiforme (GBM)

GBM is the most common and the most lethal form of brain cancer. Approximately 15,000 new cases of GBM are expected to be diagnosed in the United States during 2017. GBM progresses quickly and patients deteriorate rapidly. Common symptoms include headaches, seizures, nausea, weakness, paralysis and personality or cognitive changes such as loss of speech or difficulty in thinking clearly. The majority of GBM patients do not survive for more than two years following diagnosis, and the median survival in newly diagnosed patients with best available treatments is less than 15 months.

On April 25, 2017 Bristol-Myers Squibb Company (NYSE:BMY) and Transgene reported a new clinical research collaboration to evaluate the safety, tolerability and efficacy of Transgene’s investigational therapeutic vaccine TG4010 in combination with Bristol-Myers Squibb’s Opdivo (nivolumab) + standard chemotherapy (CT) as a first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC) in patients whose tumors have low or undetectable levels of PD-L1.

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The Phase 2 clinical trial will explore the potential of combining Transgene’s TG4010, an investigational therapeutic vaccine designed to generate an immune response against MUC1 expressing tumors such as NSCLC, in conjunction with Bristol-Myers Squibb’s immune checkpoint inhibitor, Opdivo, designed to alleviate immune suppression. Both therapies will be combined with standard chemotherapy in first line NSCLC patients. The Phase 2 trial will evaluate objective tumor responses, and disease control in patients provided the regimen of TG4010 + Opdivo + CT, whose tumors express low and undetectable levels of PD-L1. In addition, the study will evaluate safety and tolerability of this regimen together with other efficacy metrics. This multi-center single-arm trial is expected to deliver first results in 2018.

Under the terms of the agreement, Transgene will be the sponsor of the trial. Bristol-Myers Squibb will provide Opdivo for use in the study.

“We are excited to explore the potential benefits of combining Opdivo with an investigational therapeutic vaccine, TG4010, in NSCLC where the need for new therapies is particularly acute,” said Fouad Namouni, M.D., head of Oncology Development, Bristol-Myers Squibb. “As the science around cancer research continues to rapidly evolve, we are building on our leadership in Immuno-Oncology with potential combinations of therapies that may help advance new therapeutic approaches for patients in need of better options.”

“We are enthusiastic about this new collaboration with Bristol-Myers Squibb. This trial will assess the potential of Transgene’s TG4010, an investigational therapeutic vaccine that is designed to stimulate the immune system, in combination with nivolumab, Bristol-Myers Squibb’s immune checkpoint inhibitor, and standard chemotherapy. Based on the results obtained with TG4010 in a large Phase 2b trial (TIME trial) in combination with chemotherapy, we are hopeful that this triple combination regimen could provide a treatment option for patients with advanced NSCLC,” commented Philippe Archinard, Chairman and CEO Transgene.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

About TG4010

TG4010 is an immunotherapy that has been designed to express the coding sequences of the MUC1 tumor-associated antigen and the cytokine, Interleukin-2 (IL2). TG4010, which is based on a modified vaccinia virus (MVA), induces an immune response against MUC1 expressing tumors, such as non-small cell lung cancer (NSCLC).

The results from the Phase 2b TIME trial with TG4010 immunotherapy associated with chemotherapy in NSCLC have been published in the peer-reviewed medical journal, The Lancet Oncology in December 2015.

About Non-Small Cell Lung Cancer

Lung cancer is one of the most common malignancies worldwide with an estimated 1.8 million new cases annually. It is also a leading cause of cancer-related deaths, accounting for an estimated nearly 1.6 million deaths in 2012 (Source: GLOBOCAN 2012). Advanced lung cancer remains one of the cancer types with the worst prognosis (five-year survival rate for advanced NSCLC of less than 5%), underlining the still unmet need in this disease.

U. S. FDA APPROVED INDICATIONS FOR OPDIVO

OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO (nivolumab) is indicated for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests at baseline and before each dose.

Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.

Immune-Mediated Pneumonitis

OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of patients.

In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 4.9% (13/263) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 3.4% (9/263) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=8).

Immune-Mediated Colitis

OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal (diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%) patients. Across all YERVOY-treated patients in that study (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe enterocolitis.

Immune-Mediated Hepatitis

OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated hepatitis occurred in 13% (51/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5x the ULN or total bilirubin elevations >3x the ULN; Grade 3-5) occurred in 8 (2%) patients, with fatal hepatic failure in 0.2% and hospitalization in 0.4%.

Immune-Mediated Neuropathies

In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor neuropathy were reported.

Immune-Mediated Endocrinopathies

OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO with YERVOY, hypophysitis occurred in 9% (36/407) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO with YERVOY, adrenal insufficiency occurred in 5% (21/407) of patients. In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO with YERVOY, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (89/407) of patients. Hyperthyroidism occurred in 8% (34/407) of patients receiving OPDIVO with YERVOY. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients. In patients receiving OPDIVO with YERVOY, diabetes occurred in 1.5% (6/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe to life-threatening immune-mediated endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. 6 of the 9 patients were hospitalized for severe endocrinopathies.

Immune-Mediated Nephritis and Renal Dysfunction

OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated nephritis and renal dysfunction occurred in 2.2% (9/407) of patients.

Immune-Mediated Skin Adverse Reactions and Dermatitis

OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated rash occurred in 22.6% (92/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal immune-mediated dermatitis (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13 (2.5%) patients. 1 (0.2%) patient died as a result of toxic epidermal necrolysis. 1 additional patient required hospitalization for severe dermatitis.

Immune-Mediated Encephalitis

OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids. Encephalitis occurred in one patient receiving OPDIVO with YERVOY (0.2%) after 1.7 months of exposure.

Other Immune-Mediated Adverse Reactions

Based on the severity of adverse reaction, permanently discontinue or withhold treatment, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO the following clinically significant immune-mediated adverse reactions occurred in <1.0% of patients receiving OPDIVO: uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), myositis, myocarditis, rhabdomyolysis, motor dysfunction, vasculitis, and myasthenic syndrome. Infusion Reactions OPDIVO can cause severe infusion reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO monotherapy, infusion-related reactions occurred in 6.4% (127/1994) of patients. In patients receiving OPDIVO with YERVOY, infusion-related reactions occurred in 2.5% (10/407) of patients. Complications of Allogeneic HSCT after OPDIVO Complications, including fatal events, occurred in patients who received allogeneic HSCT after OPDIVO. Outcomes were evaluated in 17 patients from Checkmate 205 and 039, who underwent allogeneic HSCT after discontinuing OPDIVO (15 with reduced-intensity conditioning, 2 with myeloablative conditioning). Thirty-five percent (6/17) of patients died from complications of allogeneic HSCT after OPDIVO. Five deaths occurred in the setting of severe or refractory GVHD. Grade 3 or higher acute GVHD was reported in 29% (5/17) of patients. Hyperacute GVHD was reported in 20% (n=2) of patients. A steroid-requiring febrile syndrome, without an identified infectious cause, was reported in 35% (n=6) of patients. Two cases of encephalitis were reported: Grade 3 (n=1) lymphocytic encephalitis without an identified infectious cause, and Grade 3 (n=1) suspected viral encephalitis. Hepatic veno-occlusive disease (VOD) occurred in one patient, who received reduced-intensity conditioned allogeneic HSCT and died of GVHD and multi-organ failure. Other cases of hepatic VOD after reduced-intensity conditioned allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor blocking antibody before transplantation. Cases of fatal hyperacute GVHD have also been reported. These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT. Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene promptly. Embryo-Fetal Toxicity Based on their mechanisms of action, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with an OPDIVO- or YERVOY- containing regimen and for at least 5 months after the last dose of OPDIVO. Lactation It is not known whether OPDIVO or YERVOY is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from an OPDIVO-containing regimen, advise women to discontinue breastfeeding during treatment. Advise women to discontinue nursing during treatment with YERVOY and for 3 months following the final dose. Serious Adverse Reactions In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (73% and 37%), adverse reactions leading to permanent discontinuation (43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4 adverse reactions (72% and 44%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.6%), colitis (10% and 1.6%), and pyrexia (10% and 0.6%). In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, among all patients (safety population [n=263]), adverse reactions leading to discontinuation (4.2%) or to dosing delays (23%) occurred. The most frequent serious adverse reactions reported in ≥1% of patients were infusion-related reaction, pneumonia, pleural effusion, pyrexia, rash and pneumonitis. Ten patients died from causes other than disease progression, including 6 who died from complications of allogeneic HSCT. Serious adverse reactions occurred in 21% of patients in the safety population (n=263) and 27% of patients in the subset of patients evaluated for efficacy (efficacy population [n=95]). In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO. The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infections, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration. Common Adverse Reactions In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (59%), rash (53%), diarrhea (52%), nausea (40%), pyrexia (37%), vomiting (28%), and dyspnea (20%). The most common (≥20%) adverse reactions in the OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea (31%), and nausea (28%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were asthenic conditions (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, among all patients (safety population [n=263]) and the subset of patients in the efficacy population (n=95), respectively, the most common adverse reactions (≥20%) were fatigue (32% and 43%), upper respiratory tract infection (28% and 48%), pyrexia (24% and 35%), diarrhea (23% and 30%), and cough (22% and 35%). In the subset of patients in the efficacy population (n=95), the most common adverse reactions also included rash (31%), musculoskeletal pain (27%), pruritus (25%), nausea (23%), arthralgia (21%), and peripheral neuropathy (21%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO were cough and dyspnea at a higher incidence than investigator’s choice. In Checkmate 275, the most common adverse reactions (≥ 20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%). In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%). Checkmate Trials and Patient Populations Checkmate 067 - advanced melanoma alone or in combination with YERVOY; Checkmate 037 and 066 - advanced melanoma; Checkmate 017 - squamous non-small cell lung cancer (NSCLC); Checkmate 057 - non-squamous NSCLC; Checkmate 025 - renal cell carcinoma; Checkmate 205/039 - classical Hodgkin lymphoma; Checkmate 141 - squamous cell carcinoma of the head and neck; Checkmate 275 - urothelial carcinoma. Please see U.S. Full Prescribing Information for OPDIVO and YERVOY, including Boxed WARNING regarding immune-mediated adverse reactions for YERVOY. About the Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd. Collaboration In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Ltd (Ono), Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Bristol-Myers Squibb and Ono further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

On April 25, 2017 AstraZeneca reported that the European Commission (EC) has granted full marketing authorisation for Tagrisso (osimertinib) 40mg and 80mg once-daily tablets for the treatment of adult patients with locally-advanced or metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC) (Press release, AstraZeneca, APR 25, 2017, View Source [SID1234518677]).

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The full approval for Tagrisso is based on the results of the Phase III AURA3 trial, which were presented last year. The EGFR T790M mutation can be detected with a validated test using either DNA derived from a biopsy or circulating tumour DNA (ctDNA) obtained from a plasma sample.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "The full approval of Tagrisso in the EU is further evidence of our exciting progress in transforming the science of cancer care to deliver life-changing medicines to people most in need. Having demonstrated its superiority over chemotherapy in EGFR T790M mutation-positive non-small cell lung cancer, Tagrisso has the potential to become the new standard of care for patients with this difficult-to-treat form of lung cancer."

Data from the Phase III AURA3 trial showed that Tagrisso demonstrated statistically-significant improvements in progression-free survival (PFS) over standard platinum-based doublet chemotherapy in 419 patients with EGFR T790M-positive advanced NSCLC whose disease had progressed on or after EGFR TKI therapy. Among patients taking Tagrisso, the PFS was 10.1 months, compared to 4.4 months in the chemotherapy arm. The objective response rate (ORR) was 71% compared to 31% for chemotherapy. Among 144 patients with metastases to the central nervous system (CNS), PFS was 8.5 months versus 4.2 months.

The most common adverse reactions in the Tagrisso group were diarrhoea (41% overall; 1% Grade ≥3), rash (34% overall; 1% Grade ≥3), dry skin (23% overall; 0% Grade ≥3), paronychia (22% overall; 0% Grade ≥3), stomatitis (15% overall; 0% Grade ≥3, and pruritus (13% overall; 0% Grade ≥3). Warnings and precautions include interstitial lung disease (ILD), keratitis, left ventricular ejection fraction (LVEF) and QTc interval prolongation.

In March 2017, the US Food and Drug Administration (FDA) granted Tagrisso a conversion from accelerated to full approval. Tagrisso was also recently approved in China through the new Priority Review Pathway, which grants an accelerated review timeline for innovative therapies.

About Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths, more than breast, prostate and colorectal cancers combined. Patients who have EGFRm NSCLC, which occurs in 10-15% of NSCLC patients in the US and Europe and 30-40% of NSCLC patients in Asia, are particularly sensitive to treatment with currently available EGFR-TKIs, which block the cell signalling pathways that drive the growth of tumour cells. However, tumours almost always develop resistance to treatment, leading to disease progression. Approximately two-thirds of patients develop resistance to approved EGFR-TKIs such as gefitinib, erlotinib and afatinib due to the secondary mutation, T790M.

About Tagrisso

Tagrisso (osimertinib) 40mg and 80mg once-daily oral tablet has been approved in over 45 countries, including the US, EU, Japan and China, for patients with EGFR T790M mutation-positive advanced NSCLC. Eligibility for treatment with Tagrisso is dependent on confirmation that the EGFR T790M mutation is present in the tumour.

Tagrisso is a third generation, irreversible EGFR-TKI designed to inhibit both EGFR sensitising and EGFR T790M resistance mutations and to have activity in the CNS. Tagrisso is also being investigated in the adjuvant and metastatic 1st line settings, including in patients with and without CNS metastases, in leptomeningeal metastases, and in combination with other treatments.

About AstraZeneca in Lung Cancer

AstraZeneca uses ground-breaking science to develop a wide range of therapies for patients with lung cancer. We are pioneering biomarker-guided therapies that aim to eliminate lung cancer by targeting molecular mutations in tumour cells and by boosting the power of the immune response against cancer. We are committed to transforming outcomes for patients with lung cancer, whose treatment options are currently limited.

On April 25, 2017 Eli Lilly and Company (NYSE: LLY) reported financial results for the first quarter of 2017 (Press release, Eli Lilly, APR 25, 2017, View Source [SID1234518686]).

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$ in millions, except per share data
First Quarter
%

2017

2016
Change
Revenue
$
5,228.3


$
4,865.1

7
%
Net Income (Loss) – Reported
(110.8)


440.1

NM
Earnings (Loss) Per Share – Reported
(0.10)


0.41

NM





Net Income – Non-GAAP
1,039.6


882.3

18
%
EPS – Non-GAAP
0.98


0.83

18
%


Certain financial information for 2017 and 2016 is presented on both a reported and a non-GAAP basis. Some numbers in this press release may not add due to rounding. Reported results were prepared in accordance with generally accepted accounting principles (GAAP) and include all revenue and expenses recognized during the periods. Non-GAAP measures exclude the items described in the reconciliation tables later in the release. The company’s 2017 financial guidance is also being provided on both a reported and a non-GAAP basis. The non-GAAP measures are presented to provide additional insights into the underlying trends in the company’s business.

"Lilly’s new product launches, including Trulicity and Taltz, led the company to a strong quarter of volume-driven revenue growth. We achieved this growth while maintaining our commitment to expand margins and improve productivity," said David A. Ricks, Lilly’s president and CEO. "The progress we made in the first quarter continues the positive momentum we’ve built over the past few years. We remain on track to sustain a steady flow of innovation that has the potential to improve patients’ lives and create value for shareholders."

Key Events Over the Last Three Months

Commercial

The company and Boehringer Ingelheim launched Synjardy XR (empagliflozin and metformin hydrochloride extended-release) tablets in the U.S. for adults with type 2 diabetes. Synjardy is part of the company’s alliance with Boehringer Ingelheim.
Regulatory

With respect to Olumiant (baricitinib) on which we collaborate with Incyte:
The European Commission granted marketing authorization for 4 mg and 2 mg film-coated tablets in the European Union for the treatment of moderate-to-severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to, one or more disease-modifying antirheumatic drugs. Olumiant has been launched in select European countries.
The U.S. Food and Drug Administration (FDA) issued a complete response letter for the New Drug Application (NDA) of baricitinib, an investigational medication for the treatment of moderate-to-severe rheumatoid arthritis, indicating that the FDA is unable to approve the application in its current form. The FDA specifically stated that additional clinical data are needed to determine the most appropriate doses and to further characterize safety concerns across treatment arms.
The European Commission approved an update to the Synjardy label to include a change to the indication statement and inclusion of data on the reduction of risk of cardiovascular death in patients with type 2 diabetes and established cardiovascular disease when treated with empagliflozin.
The FDA approved updates to the label for Trulicity (dulaglutide) to include use in combination with basal insulin for adults with type 2 diabetes.
Clinical

With respect to Phase 3 trials of abemaciclib, a cyclin-dependent kinase (CDK)4 and CDK6 inhibitor, being tested in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer:
The company announced that abemaciclib, in combination with fulvestrant, in women who have relapsed or progressed after endocrine therapy was superior to fulvestrant plus placebo on progression-free survival. Lilly intends to initiate global submissions of these results, as well as for single-agent abemaciclib based on a previous Phase 2 study, beginning in the second quarter of 2017.
The company announced results of a preplanned interim analysis, evaluating abemaciclib, in combination with an aromatase inhibitor (letrozole or anastrozole), compared to treatment with an aromatase inhibitor plus placebo. The trial met its primary endpoint of demonstrating statistically significant improvement in progression-free survival. In addition, improvement was shown in a key secondary endpoint of objective response rate. Lilly intends to begin global submissions of these results in the third quarter of 2017.
The company announced that patients with moderate-to-severe plaque psoriasis treated with Taltz (ixekizumab) demonstrated superior efficacy at 24 weeks compared to patients treated with Stelara (ustekinumab).
Business Development/Other

The company completed its acquisition of CoLucid Pharmaceuticals. As a result of this acquisition, lasmiditan, in development for the acute treatment of migraine, has been added to Lilly’s Phase 3 pipeline.
The Japan IP High Court confirmed the decisions of the Japan Patent Office and ruled in Lilly’s favor in the invalidation trials initiated by Sawai regarding Lilly’s vitamin regimen patents for Alimta (pemetrexed disodium).
The company announced plans to invest $850 million in its U.S. operations in 2017. The company’s investments span facilities across its U.S. enterprise, including research laboratories, manufacturing sites, and general and administrative areas. The investments are being driven by demand for Lilly products, as well as the company’s robust pipeline of potential medicines in development targeting cancer, pain, diabetes and other unmet medical needs.
First-Quarter Reported Results

In the first quarter of 2017, worldwide revenue was $5.228 billion, an increase of 7 percent compared with the first quarter of 2016. The revenue increase was driven by an 8 percent increase due to volume, partially offset by a 1 percent decrease due to the unfavorable impact of foreign exchange rates. The increase in worldwide volume was largely due to 9 percent pharmaceutical growth driven by Trulicity, Taltz and other new products including Cyramza, LartruvoTM, Basaglar and Jardiance. To a lesser extent, the increase in volume was also driven by companion animal products due to the inclusion of $40.8 million in revenue from the acquisition of Boehringer Ingelheim Vetmedica’s U.S. feline, canine and rabies vaccine portfolio. These total volume increases were partially offset by decreased volumes for Zyprexa and Alimta.

Revenue in the U.S. increased 15 percent, to $2.934 billion, driven primarily by increased volumes for Trulicity, Taltz, Lartruvo and companion animal products due to the inclusion of revenue from the acquisition of Boehringer Ingelheim Vetmedica’s U.S. feline, canine and rabies vaccine portfolio, partially offset by decreased volume for Alimta. Realized prices increased U.S. revenue by 3 percent, primarily driven by Humalog, which had significant unfavorable changes to rebates and discounts in the first quarter of 2016 that did not recur in the first quarter of 2017.

Revenue outside the U.S. decreased 1 percent, to $2.295 billion, due to lower realized prices and volume from the loss of exclusivity for several products including Cymbalta in Canada and Europe, Zyprexa in Japan and Alimta in numerous countries, as well as the unfavorable impact of foreign exchange rates. These were largely offset by increased volume for several newly launched pharmaceutical products, including Trulicity and Cyramza.

Gross margin increased 10 percent, to $3.901 billion, in the first quarter of 2017 compared with the first quarter of 2016. Gross margin as a percent of revenue was 74.6 percent, an increase of 1.8 percentage points compared with the first quarter of 2016. The increase in gross margin percent was primarily due to manufacturing efficiencies.

Operating expenses in the first quarter of 2017, defined as the sum of research and development, and marketing, selling and administrative expenses, were $2.783 billion, an increase of 3 percent compared with the first quarter of 2016. Research and development expenses increased 1 percent, to $1.238 billion, or 23.7 percent of revenue. Marketing, selling and administrative expenses increased 5 percent, to $1.545 billion, due to increased expenses related to new pharmaceutical products, partially offset by decreased expenses related to late life-cycle products. Operating expenses were 53.2 percent of revenue in the first quarter of 2017, a reduction of 2.2 percentage points compared with the first quarter of 2016.

In the first quarter of 2017, the company recognized an acquired in-process research and development charge of $857.6 million associated with the acquisition of CoLucid Pharmaceuticals. There were no acquired in-process research and development charges in the first quarter of 2016.

In the first quarter of 2017, the company recognized asset impairment, restructuring and other special charges of $213.9 million, primarily related to severance costs incurred as a result of actions taken to reduce the company’s cost structure, as well as integration costs related to the acquisition of Novartis Animal Health. In the first quarter of 2016, the company recognized asset impairment, restructuring and other special charges of $131.4 million, composed of asset impairments related to the closure of an animal health manufacturing facility in Ireland and integration costs related to the acquisition of Novartis Animal Health.

Operating income in the first quarter of 2017 was $46.1 million, a decrease of $669.7 million compared with the first quarter of 2016, primarily driven by an acquired in-process research and development charge for the acquisition of CoLucid Pharmaceuticals, partially offset by revenue growth.

Other income (expense) was income of $15.1 million in the first quarter of 2017, compared with expense of $149.0 million in the first quarter of 2016. Other expense in the first quarter of 2016 was driven by a $203.9 million charge related to the impact of the Venezuelan financial crisis.

During the first quarter of 2017, the company incurred $172.0 million of income tax expense, despite earning $61.2 million of income before income taxes, as a result of the nondeductible $857.6 million acquired in-process research and development charge for the acquisition of CoLucid Pharmaceuticals. During the first quarter of 2016, the company’s effective tax rate was 22.4 percent.

In the first quarter of 2017, net income (loss) and earnings (loss) per share were $(110.8) million and $(0.10), respectively, compared with $440.1 million and $0.41, respectively, in the first quarter of 2016. These decreases in net income (loss) and earnings (loss) per share were primarily driven by lower operating income, partially offset by higher other income.

First-Quarter Non-GAAP Measures

On a non-GAAP basis, first quarter 2017 gross margin increased 10 percent, to $4.085 billion. Gross margin as a percent of revenue was 78.1 percent, an increase of 1.8 percentage points compared with the first quarter of 2016. The increase in gross margin percent was primarily due to manufacturing efficiencies.

Operating expenses were 53.2 percent of revenue in the first quarter of 2017, a reduction of 2.2 percentage points compared with the first quarter of 2016.

Operating income increased $284.4 million, or 28 percent, to $1.304 billion in the first quarter of 2017, due to revenue growth, partially offset by higher operating costs related to new products.

The effective tax rate was 21.2 percent in the first quarter of 2017, compared with 17.9 percent in the first quarter of 2016. The higher effective tax rate for the first quarter of 2017 was primarily due to a net discrete tax benefit of approximately $50 million in 2016.

In the first quarter of 2017, net income and earnings per share increased 18 percent, to $1.040 billion, and $0.98, respectively, compared with $882.3 million, and $0.83, respectively, in the first quarter of 2016. The increases in net income and earnings per share were primarily driven by higher operating income, partially offset by a higher effective tax rate and lower other income.

For further detail of non-GAAP measures, see the reconciliation below as well as the Reconciliation of GAAP Reported to Selected Non-GAAP Adjusted Information table later in this press release.




First Quarter

2017

2016
% Change
Earnings (loss) per share (reported)
$
(0.10)


$
0.41

NM
Acquired in-process research and development
.81


—


Asset impairment, restructuring and other special charges
.16


.11


Amortization of intangible assets
.11


.11


Inventory step up costs associated with the acquisition of
Boehringer Ingelheim Vetmedica’s U.S. feline, canine and
rabies vaccines portfolio
.01


—


Venezuela charge
—


.19


Earnings per share (non-GAAP)
$
0.98


$
0.83

18%





Numbers may not add due to rounding.








Select Revenue Highlights






(Dollars in millions)

First Quarter




Established Pharmaceutical Products
2017

2016


% Change

Humalog
$
708.4


$
606.3


17%

Cialis
533.6


576.7


(7)%

Alimta
489.9


564.2


(13)%

Forteo
347.5


318.6


9%

Humulin
314.5


356.4


(12)%

Strattera
196.2


188.1


4%

Cymbalta
174.6


198.7


(12)%

Erbitux
154.4


168.1


(8)%

Zyprexa
147.5


212.8


(31)%

Effient
127.8


131.5


(3)%








New Pharmaceutical Products






Trulicity
372.9


143.6


160%

Cyramza
171.2


131.0


31%

Taltz
96.6


—


NM

Jardiance(a)
74.0


38.2


94%

Basaglar
46.0


10.9


321%

Lartruvo
42.1


—


NM

Portrazza
3.6


1.7


108%

Olumiant
1.9


—


NM

Subtotal
808.3


325.4


148%








Animal Health
769.4


754.6


2%








Total Revenue
5,228.3


4,865.1


7%








(a) Jardiance includes Glyxambi and Synjardy
NM – not meaningful
Numbers may not add due to rounding


Selected Established Pharmaceutical Products

Humalog

For the first quarter of 2017, worldwide Humalog revenue increased 17 percent compared with the first quarter of 2016, to $708.4 million. Revenue in the U.S. increased 24 percent, to $449.1 million, primarily driven by decreased revenue in the first quarter of 2016 resulting from changes in estimates for rebates and discounts, and to a lesser extent increased demand. Revenue outside the U.S. increased 6 percent, to $259.4 million, driven by increased volume and, to a lesser extent, higher realized prices, partially offset by the unfavorable impact of foreign exchange rates.

Cialis

For the first quarter of 2017, worldwide Cialis revenue decreased 7 percent, to $533.6 million. U.S. revenue of Cialis was $296.7 million in the first quarter, an 8 percent decrease compared with the first quarter of 2016, driven by decreased demand. Revenue of Cialis outside the U.S. decreased 6 percent, to $236.9 million, driven by decreased volume and, to a lesser extent, the unfavorable impact of foreign exchange rates, partially offset by higher realized prices.

Alimta

For the first quarter of 2017, Alimta generated worldwide revenue of $489.9 million, which decreased 13 percent compared with the first quarter of 2016. U.S. revenue of Alimta decreased 14 percent, to $227.3 million, driven by decreased demand due to competitive pressure. Revenue outside the U.S. decreased 13 percent, to $262.6 million, driven by lower realized prices, the loss of exclusivity in several countries and, to a lesser extent, the unfavorable impact of foreign exchange rates.

Forteo

First-quarter 2017 worldwide revenue for Forteo was $347.5 million, a 9 percent increase compared with the first quarter of 2016. U.S. revenue increased 20 percent, to $177.7 million, driven by higher realized prices and, to a lesser extent, wholesaler buying patterns. Revenue outside the U.S. remained flat at $169.8 million, driven by lower realized prices, offset by increased volume.

Humulin

Worldwide Humulin revenue for the first quarter of 2017 decreased 12 percent compared with the first quarter of 2016 to $314.5 million. U.S. revenue decreased 14 percent, to $205.4 million, driven by a change in the estimate in 2016 for a government rebate, which increased revenue in that period, and to a lesser extent, decreased demand. Revenue outside the U.S. decreased 6 percent, to $109.1 million, driven by lower realized prices and, to a lesser extent, the unfavorable impact of foreign exchange rates, partially offset by increased volume.

Selected New Pharmaceutical Products

Trulicity

First-quarter 2017 worldwide Trulicity revenue was $372.9 million. U.S. revenue was $296.3 million, driven by growth in the GLP-1 market and increased share of market for Trulicity. Revenue outside the U.S. was $76.6 million, primarily driven by uptake in Europe and Japan.

Cyramza

For the first quarter of 2017, worldwide Cyramza revenue was $171.2 million, an increase of 31 percent compared with the first quarter of 2016. U.S. revenue was $66.2 million, a decrease of 8 percent, driven by lower realized prices and, to a lesser extent, decreased demand due to competitive pressure. Revenue outside the U.S. was $105.1 million, an increase of 77 percent, primarily due to strong volume growth in Japan, partially offset by lower realized prices.

Taltz

For the first quarter of 2017, Taltz, a treatment for moderate-to-severe plaque psoriasis, generated worldwide revenue of $96.6 million. U.S. revenue was $87.8 million, an increase of $28.4 million compared with the fourth quarter of 2016, reflecting strong launch uptake.

Jardiance

The company’s worldwide Jardiance revenue during the first quarter of 2017 was $74.0 million, an increase of 94 percent compared with the first quarter of 2016. U.S. revenue increased 60 percent, to $47.7 million, driven by increased share of market for Jardiance and growth in the SGLT2 class. Revenue outside the U.S. was $26.2 million. Jardiance is part of the company’s alliance with Boehringer Ingelheim, and Lilly reports as revenue a portion of Jardiance’s gross margin.

Basaglar

For the first quarter of 2017, Basaglar generated worldwide revenue of $46.0 million. U.S. revenue was $22.0 million. Basaglar is part of the company’s alliance with Boehringer Ingelheim, and Lilly reports as revenue total sales, with payments made to Boehringer Ingelheim for its portion of the gross margin reported as cost of sales.

Lartruvo

For the first quarter of 2017, Lartruvo, a treatment in combination with doxorubicin for a subset of adult patients with advanced soft tissue sarcoma, generated worldwide revenue of $42.1 million. U.S. revenue was $38.1 million, an increase of $26.7 million compared with the fourth quarter of 2016.

Olumiant

For the first quarter of 2017, Olumiant, a treatment for moderate-to-severe rheumatoid arthritis, generated worldwide revenue of $1.9 million, reflecting initial sales in Germany.

Animal Health

In the first quarter of 2017, worldwide animal health revenue totaled $769.4 million, an increase of 2 percent compared with the first quarter of 2016. Worldwide food animal revenue decreased 3 percent, to $508.1 million, driven by lower worldwide volume due to continued economic pressure in the dairy market and customer buying patterns. Worldwide companion animal revenue increased 13 percent, to $261.3 million, driven by the inclusion of $40.8 million in revenue from the acquisition of Boehringer Ingelheim Vetmedica’s U.S. feline, canine and rabies vaccine portfolio, partially offset by worldwide competitive pressure.

2017 Financial Guidance

Earnings per share for 2017 are being revised to be in the range of $2.60 to $2.70 on a reported basis, due to severance costs incurred as a result of actions taken to reduce the company’s cost structure. Earnings per share for 2017 are being reaffirmed to be $4.05 to $4.15 on a non-GAAP basis.




2017
Expectations
% Change
from 2016
Earnings per share (reported)
$2.60 to $2.70
1% to 5%
Acquired in-process research and development charge related to
the acquisition of CoLucid Pharmaceuticals
.81

Amortization of intangible assets (1)
.44

Asset impairment, restructuring and other special charges,
including Novartis Animal Health integration costs
.17

Inventory step-up costs associated with the acquisition of
Boehringer Ingelheim Vetmedica’s U.S. feline, canine and rabies
vaccines portfolio (1)
.02

Earnings per share (non-GAAP)
$4.05 to $4.15
15% to 18%
(1) Subject to acquisition accounting adjustments


Numbers may not add due to rounding




The company still anticipates 2017 revenue between $21.8 billion and $22.3 billion. Excluding the impact of foreign exchange rates, the company expects revenue growth from animal health products and a number of established pharmaceutical products including Trajenta, Forteo and Humalog, as well as higher revenue from new products including Trulicity, Taltz, Basaglar, Cyramza, Jardiance and Lartruvo.

Marketing, selling and administrative expenses are still expected to be in the range of $6.4 billion to $6.6 billion. Research and development expenses are still expected to be in the range of $4.9 billion to $5.1 billion.

The 2017 tax rate is still expected to be approximately 24.5 percent on a reported basis and 22.0 percent on a non-GAAP basis.

The following table summarizes the company’s 2017 financial guidance:




2017 Guidance

Prior

Revised
Revenue
$21.8 to $22.3 billion

Unchanged




Gross Margin % of Revenue (reported)
Approx. 73.5%

Unchanged
Gross Margin % of Revenue (non-GAAP)
Approx. 77.0%

Unchanged




Marketing, Selling & Administrative
$6.4 to $6.6 billion

Unchanged




Research & Development
$4.9 to $5.1 billion

Unchanged




Other Income/(Expense)
$0 to $100 million

Unchanged




Tax Rate (reported)
Approx. 24.5%

Unchanged
Tax Rate (non-GAAP)
Approx. 22.0%

Unchanged




Earnings per Share (reported)
$2.69 to $2.79

$2.60 to $2.70
Earnings per Share (non-GAAP)
$4.05 to $4.15

Unchanged




Capital Expenditures
Approx. $1.2 billion

Unchanged




Non-GAAP adjustments are consistent with the earnings per share table above.