On April 19, 2016 Merck (NYSE: MRK), known as MSD outside the United States and Canada, is proud to be a part of the Blueprint PD-L1 Assay Comparison Project, an important initiative to compare several new diagnostic tests for the immune biomarker PD-L1 in non-small cell lung cancer (NSCLC) (Press release, Merck & Co, APR 19, 2016, View Source [SID:1234511085]).

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Merck believes strongly in the importance of PD-L1 testing in NSCLC, and is committed to supporting the Blueprint Project and overall efforts to use diagnostics to help physicians identify the best treatment approach for their patients with some cancers.

In oncology, testing is now common for numerous cancer biomarkers to enable physicians to better tailor treatment decisions for each patient. The data from a range of studies, including Merck’s studies of KEYTRUDA (pembrolizumab), demonstrate that PD-L1 testing can be a useful tool to help identify patients more likely to respond to treatment with an anti-PD-1/PD-L1 therapy in certain cancers, including NSCLC.

Phase 1 of the Blueprint Project is an important step toward understanding the usefulness of the different PD-L1 testing approaches. Analyses from the Blueprint Project confirm that there is high concordance for the two approved PD-L1 diagnostics in NSCLC, including the one used in conjunction with KEYTRUDA, the PD-L1 IHC 22C3 pharmDx assay developed in partnership with Dako North America, Inc., an Agilent Technologies Company.

"We are very encouraged by the findings from the Blueprint Project, and are eager to support the greater use of biomarker testing to advance the care of patients with cancer," said Dr. Roy Baynes, senior vice president and head of global clinical development, Merck Research Laboratories. "This analysis reinforces our precision medicine approach in NSCLC to help provide physicians and patients with greater insight into each patient’s disease and therefore greater confidence in their treatment decisions."

Merck is a leader in advancing immuno-oncology through the development of KEYTRUDA (pembrolizumab) alongside its Dako companion diagnostic. We are continuing to build our knowledge of genetics and biomarkers in order to ensure we can match KEYTRUDA with patients who are more likely to experience benefit.

About the Blueprint Project

Results from the Blueprint Project, a first-of-its kind collaboration, were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2016 Annual Meeting.

In March 2015, the AACR (Free AACR Whitepaper) in partnership with the U.S. Food and Drug Administration and the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) held a one-day workshop to examine whether multiple companion diagnostics intended for the same class of therapeutics could be harmonized. During the workshop, a group of four pharmaceutical companies and two diagnostic companies released a blueprint proposal to analytically compare and characterize each of their IHC-based PD-1/PD-L1 companion diagnostics for non-small cell lung cancer in the pre-approval stage. The thought was that, upon approval of these tests, the information generated by this project could lay the groundwork for additional studies that will help inform patients, physicians, pathologists, and others on how best to use the test results to determine treatment decisions.

About KEYTRUDA (pembrolizumab) Injection 100 mg

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

KEYTRUDA is indicated in the United States for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is also indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA. The NSCLC indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

KEYTRUDA (pembrolizumab) is administered at a dose of 2 mg/kg as an intravenous infusion over 30 minutes every three weeks for the approved indications.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

Immune-mediated pneumonitis occurred in 19 (3.5%) of 550 patients, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneumonitis and occurred more frequently in patients with a history of asthma/chronic obstructive pulmonary disease (5.4%) or prior thoracic radiation (6.0%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-mediated colitis occurred in 4 (0.7%) of 550 patients, including Grade 2 (0.2%) or 3 (0.4%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-mediated hepatitis occurred in patients receiving KEYTRUDA. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hypophysitis occurred in 1 (0.2%) of 550 patients, which was Grade 3 in severity. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

Hyperthyroidism occurred in 10 (1.8%) of 550 patients, including Grade 2 (0.7%) or 3 (0.3%) hyperthyroidism. Hypothyroidism occurred in 38 (6.9%) of 550 patients, including Grade 2 (5.5%) or 3 (0.2%) hypothyroidism. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 3 (0.1%) of 2117 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA (pembrolizumab) and administer anti-hyperglycemics in patients with severe hyperglycemia.

Immune-mediated nephritis occurred in patients receiving KEYTRUDA. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

Other clinically important immune-mediated adverse reactions can occur. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of 550 patients: rash, vasculitis, hemolytic anemia, serum sickness, and myasthenia gravis.

Severe and life-threatening infusion-related reactions have been reported in 3 (0.1%) of 2117 patients. Monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

KEYTRUDA was discontinued due to adverse reactions in 14% of 550 patients. Serious adverse reactions occurred in 38% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. The most common adverse reactions (reported in at least 20% of patients) were fatigue (44%), cough (29%), decreased appetite (25%), and dyspnea (23%).

No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA (pembrolizumab).

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck Oncology, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

On April 19, 2016 Pfizer Inc. (NYSE:PFE) reported positive top-line results from the Phase 3 PALOMA-2 trial for IBRANCE (palbociclib), an oral, first-in-class inhibitor of cyclin-dependent kinases (CDKs) 4 and 6 (Press release, Pfizer, APR 19, 2016, View Source [SID:1234511074]).1

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

"PALOMA-2 represents the third randomized study to demonstrate the benefit of IBRANCE when added to hormonal therapy in the management of women with ER+, HER2- advanced breast cancer. IBRANCE remains the only CDK 4/6 inhibitor with Phase 3 data in this disease," said Dr. Mace Rothenberg, MD, chief medical officer, Pfizer Oncology & senior vice president, Global Product Development, Oncology. "These results provide confirmatory evidence for PALOMA-1 and will be used to support regulatory submissions around the world, including a request for conversion of IBRANCE from accelerated to full approval in the United States. We look forward to sharing the detailed results of PALOMA-2 with the oncology community and advancing our discussions with regulatory authorities."
The adverse events observed with IBRANCE in combination with letrozole in PALOMA-2 were generally consistent with the known safety profile for IBRANCE across the different patient populations and lines of therapy in the clinical development program to date. The warnings and precautions of IBRANCE include neutropenia, pulmonary embolism and embryo-fetal toxicity.1 For more information, please see Important Safety Information for IBRANCE below.1

Since its introduction in February 2015, more than 25,000 women have been prescribed IBRANCE by more than 6,000 prescribers in the U.S.

Based on the results of PALOMA-1, IBRANCE first was approved by the U.S. Food and Drug Administration (FDA) in February 2015 for the treatment of postmenopausal women with ER+, HER2- advanced breast cancer in combination with letrozole as initial endocrine-based therapy for their metastatic disease.1 The indication in combination with letrozole was approved under accelerated approval based on PFS. As stated at the time of the approval, continued approval for this indication may be contingent upon verification and description of clinical benefit in PALOMA-2, which the FDA identified as the confirmatory trial.1 Pfizer will work with the FDA to submit the results of PALOMA-2 to support conversion of the accelerated approval for IBRANCE to regular approval in the U.S.

As previously announced in February 2016, IBRANCE also is approved in the U.S. for the treatment of hormone receptor-positive (HR+), HER2-advanced or metastatic breast cancer in combination with fulvestrant in women with disease progression following endocrine therapy based on results from the Phase 3 PALOMA-3 study.1

IBRANCE also is approved in eight countries outside of the U.S., and Pfizer will work with additional global regulatory authorities to review the PALOMA-2 data. As previously disclosed in August 2015, Pfizer has filed a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) for IBRANCE in combination with endocrine therapy for the treatment of HR+, HER2- advanced or metastatic breast cancer. The MAA was based on the results from the PALOMA-1 and PALOMA-3 trials. Pfizer will work with the EMA to submit the PALOMA-2 results as additional supporting data for the ongoing review of the MAA.

About the PALOMA Trials

Pfizer has worked closely with investigators and international breast cancer experts to establish a robust development program for IBRANCE in HR+, HER2- breast cancer across stages and treatment settings.

PALOMA-1

PALOMA-1 is a randomized (1:1), multi-center, multinational, open label Phase 2 trial designed to assess PFS in postmenopausal women with ER+, HER2- advanced breast cancer receiving IBRANCE (125 mg once daily for three out of four weeks in repeated cycles) in combination with letrozole versus letrozole alone (2.5 mg once daily on a continuous regimen) as a first-line treatment. The results from PALOMA-1 were published online by The Lancet Oncology in December 2014.
PALOMA-2

PALOMA-2 is a randomized (2:1), multicenter, multinational, double-blind Phase 3 study designed to assess PFS in postmenopausal women with ER+, HER2- advanced breast cancer receiving IBRANCE (125 mg orally once daily for three out of four weeks in repeated cycles) in combination with letrozole (2.5 mg once daily continuously) versus letrozole plus placebo as a first-line treatment. PALOMA-2 has more than 200 global sites participating and 666 patients enrolled.
PALOMA-3

PALOMA-3 is a randomized (2:1), multicenter, multinational, double-blind Phase 3 study designed to assess PFS with IBRANCE (125 mg once daily orally for three out of four weeks in each cycle) in combination with fulvestrant (500 mg intramuscularly on days 1 and 15 of cycle 1, and then on day 1 of each subsequent 28 day cycle) versus fulvestrant plus placebo in pre/perimenopausal and postmenopausal women with HR+, HER2- metastatic breast cancer whose disease has progressed during or after endocrine therapy. Based on the PALOMA-3 results, a supplemental New Drug Application (sNDA) was reviewed and approved in February 2016 under the FDA’s Breakthrough Therapy designation and Priority Review programs to expand the use of IBRANCE to include use in combination with fulvestrant in women with HR+, HER2- advanced or metastatic breast cancer with disease progression following endocrine therapy.1
The full prescribing information for IBRANCE can be found at www.pfizer.com.

Important Safety Information

Neutropenia was the most frequently reported adverse reaction in Study 1 (PALOMA-1) (75%) and Study 2 (PALOMA-3) (83%). In Study 1, Grade 3 (57%) or 4 (5%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In Study 2, Grade 3 (56%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in about 1% of patients exposed to IBRANCE. One death due to neutropenic sepsis was observed in Study 2. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 14 of first 2 cycles, and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Pulmonary embolism (PE) has been reported at a higher rate in patients treated with IBRANCE plus letrozole in Study 1 (5%) and in patients treated with IBRANCE plus fulvestrant in Study 2 (1%) compared with no cases in patients treated either with letrozole alone or fulvestrant plus placebo. Monitor for signs and symptoms of PE and treat as medically appropriate.

Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants.

The most common adverse reactions (≥10%) of any grade reported in Study 1 of IBRANCE plus letrozole vs letrozole alone included neutropenia (75% vs 5%), leukopenia (43% vs 3%), fatigue (41% vs 23%), anemia (35% vs 7%), upper respiratory infection (31% vs 18%), nausea (25% vs 13%), stomatitis (25% vs 7%), alopecia (22% vs 3%), diarrhea (21% vs 10%), thrombocytopenia (17% vs 1%), decreased appetite (16% vs 7%), vomiting (15% vs 4%), asthenia (13% vs 4%), peripheral neuropathy (13% vs 5%), and epistaxis (11% vs 1%).

Grade 3/4 adverse reactions (≥10%) in Study 1 reported at a higher incidence in the IBRANCE plus letrozole group vs the letrozole alone group included neutropenia (54% vs 1%) and leukopenia (19% vs 0%). The most frequently reported serious adverse events in patients receiving IBRANCE plus letrozole were pulmonary embolism (4%) and diarrhea (2%).

Lab abnormalities occurring in Study 1 (all grades, IBRANCE plus letrozole vs letrozole alone) were decreased WBC (95% vs 26%), decreased neutrophils (94% vs 17%), decreased lymphocytes (81% vs 35%), decreased hemoglobin (83% vs 40%), and decreased platelets (61% vs 16%).

The most common adverse reactions (≥10%) of any grade reported in Study 2 of IBRANCE plus fulvestrant vs fulvestrant plus placebo included neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), headache (26% vs 20%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), constipation (20% vs 16%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

Grade 3/4 adverse reactions (≥10%) in Study 2 reported at a higher incidence in the IBRANCE plus fulvestrant group vs the fulvestrant plus placebo group included neutropenia (66% vs 1%) and leukopenia (31% vs 2%). The most frequently reported serious adverse reactions in patients receiving IBRANCE plus fulvestrant were infections (3%), pyrexia (1%), neutropenia (1%), and pulmonary embolism (1%).

Lab abnormalities occurring in Study 2 (all grades, IBRANCE plus fulvestrant vs fulvestrant plus placebo) were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), and decreased platelets (62% vs 10%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg/day. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure.

IBRANCE has not been studied in patients with moderate to severe hepatic impairment or in patients with severe renal impairment (CrCl <30 mL/min).

About IBRANCE (palbociclib) 125mg capsules

IBRANCE is an oral inhibitor of CDKs 4 and 6,1 which are key regulators of the cell cycle that trigger cellular progression.3,4 IBRANCE is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with letrozole as initial endocrine based therapy in postmenopausal women, or fulvestrant in women with disease progression following endocrine therapy.1 The indication in combination with letrozole is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.1

On April 19, 2016 Oncothyreon Inc. (NASDAQ:ONTY), a clinical-stage biopharmaceutical company, reported the presentation of data highlighting the preclinical development of orally bioavailable, potent and selective checkpoint kinase 1 (Chk1) inhibitors (Press release, Oncothyreon, APR 19, 2016, View Source [SID:1234511061]).

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Results were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 in New Orleans.

Chk1 is a protein kinase that plays a major role in the ability of cancer cells to respond to DNA damage and DNA replication stress. As a single agent, Chk1 inhibitors may selectively target cancer cells that have high replication stress, which can be caused by activation of oncogenic signaling and loss of tumor suppressor functions. Chk1 inhibitors may also be used in combination with chemotherapy, potentially enhancing cell death and increasing the efficacy of these agents.

"The research presented at AACR (Free AACR Whitepaper) describes the results of our efforts to identify highly potent and selective, orally bioavailable Chk1 inhibitors with compelling single-agent and combinatorial anti-tumor activity," said Scott Peterson, Ph.D, Chief Scientific Officer of Oncothyreon. "We believe the Chk1 program warrants further study as part of our strategy to develop a pipeline of novel, orally available, targeted agents designed to improve the lives and outcomes of patients with cancer."

The Oncothyreon presentation, titled "Discovery and development of orally available subnanomolar potent checkpoint kinase 1 inhibitors as potential anticancer therapies" (Abstract #2721), highlights preclinical data demonstrating that select Chk1 inhibitors display subnanomolar biochemical and single-digit nanomolar cellular potency against Chk1. In addition, Oncothyreon Chk1 inhibitors are active against a diverse range of cancer cell lines derived from leukemias, lymphomas and solid tumors, and demonstrate synergistic activity in combination with the chemotherapeutic drugs gemcitabine or cytarabine. The pharmaceutical properties of the Chk1 inhibitors also indicate good metabolic stability and pharmacokinetic properties, with good oral bioavailability in preclinical models, which may allow for the development of optimized dosing schedules.

The research was conducted pursuant to a research collaboration agreement with Sentinel Oncology.

On April 19, 2016 Johnson & Johnson (NYSE: JNJ) reported sales of $17.5 billion for the first quarter of 2016, an increase of 0.6% as compared to the first quarter of 2015 (Press release, Johnson & Johnson, APR 19, 2016, View Source [SID:1234511056]).

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Operational sales results increased 3.9% and the negative impact of currency was 3.3%. Domestic sales increased 7.2%. International sales decreased 6.0%, reflecting operational growth of 0.6% and a negative currency impact of 6.6%. Excluding the net impact of acquisitions, divestitures and hepatitis C sales, on an operational basis, worldwide sales increased 6.9%, domestic sales increased 9.8% and international sales increased 3.8%.* The currency devaluation in Venezuela negatively impacted worldwide operational sales growth by 60 basis points, and international sales growth by 120 basis points.

Net earnings and diluted earnings per share for the first quarter of 2016 were $4.3 billion and $1.54, respectively. First quarter 2016 net earnings included after-tax intangible amortization expense of approximately $0.2 billion and a charge for after-tax special items of approximately $0.2 billion. First quarter 2015 net earnings included after-tax intangible amortization expense of approximately $0.2 billion and a net gain for after-tax special items of approximately $0.1 billion. A reconciliation of non-GAAP financial measures is included as an accompanying schedule. Excluding after-tax intangible amortization expense and special items, adjusted net earnings for the current quarter were $4.7 billion and adjusted diluted earnings per share were $1.68, representing increases of 6.1% and 7.7%, respectively, as compared to the same period in 2015.* On an operational basis, adjusted diluted earnings per share increased 10.3%.*

"We are off to a strong start to the year, supported by our first quarter underlying sales growth," said Alex Gorsky, Chairman and Chief Executive Officer. "Our Pharmaceuticals business continues to deliver impressive levels of growth, we have steady improvement in our Consumer business, and we are seeing momentum in our Medical Devices businesses, all of which are fueling our optimism for the full-year ahead."

Mr. Gorsky continued, "I am proud of our global teams for their contributions to these results and their commitment to developing innovative solutions that address the unmet health care needs of people around the world."

The Company updated its sales guidance for the full-year 2016 to $71.2 billion to $71.9 billion reflecting current foreign currency exchange rates. Additionally, the Company increased its adjusted earnings guidance for full-year 2016 to $6.53 – $6.68 per share.

Worldwide Consumer sales of $3.2 billion for the first quarter 2016 represented a decrease of 5.8% versus the prior year, consisting of an operational decrease of 0.2% and a negative impact from currency of 5.6%. Domestic sales decreased 0.1%; international sales decreased 9.6%, which reflected an operational decrease of 0.3% and a negative currency impact of 9.3%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 1.9%, domestic sales increased 4.1% and international sales increased 0.5%*. The currency devaluation in Venezuela negatively impacted worldwide Consumer operational sales growth by 200 basis points, and international sales growth by 320 basis points.

Primary contributors to Consumer operational sales results were over-the-counter products including TYLENOL and MOTRIN analgesics, upper respiratory products including ZYRTEC allergy medications, digestive health products, domestic LISTERINE oral care products and international anti-smoking aids.

Worldwide Pharmaceutical sales of $8.2 billion for the first quarter 2016 represented an increase of 5.9% versus the prior year with an operational increase of 8.5% and a negative impact from currency of 2.6%. Domestic sales increased 12.9%; international sales decreased 3.4%, which reflected an operational increase of 2.6% and a negative currency impact of 6.0%. Excluding the net impact of acquisitions, divestitures and hepatitis C sales, on an operational basis, worldwide sales increased 12.3%, domestic sales increased 16.2% and international sales increased 7.1%.*

Worldwide operational sales growth was driven by new products and the strength of core products. New product sales growth was negatively impacted by lower sales of OLYSIO/SOVRIAD (simeprevir) due to competitive entrants. Strong growth in new products include IMBRUVICA (ibrutinib), an oral, once-daily therapy approved for use in treating certain B-cell malignancies, a type of blood or lymph node cancer; XARELTO (rivaroxaban), an oral anticoagulant; DARZALEX (daratumumab), for the treatment of patients with multiple myeloma; and INVOKANA/INVOKAMET (canagliflozin), for the treatment of adults with type 2 diabetes.

Additional contributors to operational sales growth include REMICADE (infliximab) and SIMPONI/SIMPONI ARIA (golimumab), biologics approved for the treatment of a number of immune-mediated inflammatory diseases; STELARA (ustekinumab), a biologic approved for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis; and INVEGA SUSTENNA/XEPLION/TRINZA (paliperidone palmitate), long-acting, injectable atypical antipsychotics for the treatment of schizophrenia in adults.

During the quarter, the U.S. Food and Drug Administration (FDA) approved an additional indication for IMBRUVICA (ibrutinib) for first-line treatment of chronic lymphocytic leukemia. The Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion recommending a conditional marketing authorization in the European Union for first-in-class CD38 immunotherapy DARZALEX (daratumumab), for the treatment of patients with multiple myeloma, as well as a positive opinion recommending marketing authorization for TREVICTA (paliperidone palmitate a 3-monthly injection) for the maintenance treatment of schizophrenia.

In April, subsequent to the first quarter, a worldwide collaboration and license agreement was entered into with TESARO, Inc. for exclusive rights to the investigational compound niraparib in prostate cancer.

Worldwide Medical Devices sales of $6.1 billion for the first quarter 2016 represented a decrease of 2.4% versus the prior year consisting of an operational increase of 0.5% and a negative currency impact of 2.9%. Domestic sales increased 2.2%; international sales decreased 6.5%, which reflected an operational decrease of 1.0% and a negative currency impact of 5.5%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 3.0%, domestic sales increased 3.3% and international sales increased 2.8%.*

Primary contributors to operational sales growth were electrophysiology products in the Cardiovascular business; joint reconstruction products in the Orthopaedics business; endocutters, energy and biosurgical products in the Advanced Surgery business; and international ACUVUE contact lenses in the Vision Care business.

In April, subsequent to the quarter, the acquisition of NeuWave Medical, Inc., a privately held medical device company that manufactures and markets minimally invasive soft tissue microwave ablation systems, was completed.

On April 19, 2016 ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) reported the results of comprehensive preclinical studies on its investigational tyrosine kinase inhibitor (TKI), AP32788, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 (Press release, Ariad, APR 19, 2016, View Source [SID:1234511048]). AP32788 is a TKI designed to target specific mutations in EGFR or HER2 present in a subset of patients with non-small cell lung cancer (NSCLC), for whom there are currently no targeted therapies available. The Phase 1/2 clinical trial of AP32788 is expected to begin patient enrollment in the second quarter of 2016.

The data presented were included in an oral presentation entitled, “AP32788, a potent, selective inhibitor of EGFR and HER2 oncogenic mutants, including exon 20 insertions, in preclinical models.” The research conducted by ARIAD scientists showed that in a matched set of engineered cell lines, AP32788 inhibited all tested EGFR and HER2 mutants, including exon 20 insertion mutants, with selectivity over wild-type (WT) EGFR. Inhibition of WT EGFR in non-tumor cells has been associated with dose-limiting toxicities of EGFR inhibitors in patients. Enzymatic analysis confirmed that AP32788 irreversibly inactivated EGFR exon 20 with 20-fold selectivity over WT EGFR, in contrast to other tested EGFR TKIs. AP32788 also induced tumor regressions in a mouse EGFR exon 20 model at doses that were well tolerated.

“These preclinical data on AP32788 demonstrate its potential to potently inhibit exon 20 mutant forms of EGFR and HER2, that are not addressed by currently available TKI treatments,” said Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. “The selectivity data suggest that efficacious levels of exposure to AP32788 may be achievable in patients with these challenging mutations —a hypothesis we will be testing in the Phase 1/2 trial. We believe AP32788 is the first TKI that has been designed and optimized to inhibit the underlying mutation present in these orphan oncology disease subsets.”

About Non-Small Cell Lung Cancer, EGFR and HER2

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85 percent of the estimated 221,200 new cases of lung cancer diagnosed in 2015 in the United States, according to the American Cancer Society. EGFR mutations represent the largest known, targetable subset of NSCLC. While the most common types of EGFR mutation are addressed by approved TKI therapies, there are no targeted treatment options available for the approximately 4 to 9 percent of EGFR-mutated lung tumors with exon 20 insertion mutations1. In addition, patients with HER2 mutations, mostly exon 20 insertion mutations, comprise approximately 2 percent of NSCLC patients2 and also have no current treatment options. ARIAD estimates that there are approximately 6,000 patients in the United States living with EGFR exon 20 or HER2 point mutations, based on available data from 2014 on the number of Stage IIIB or IV NSCLC and the estimated percentage of patients with these mutations.

About AP32788

AP32788 is an investigational oral tyrosine kinase inhibitor (TKI) of activating mutations in EGFR and HER2. The molecule was designed to address the unmet need in patients with non-small cell lung cancer (NSCLC) driven by exon 20 insertion mutations in EGFR and HER2, and is ARIAD’s fourth internally discovered oncology IND to be cleared for clinical development.