On February 1, 2017 Bristol-Myers Squibb Company (NYSE: BMY) reported that the European Patent Office (EPO) upheld a decision with regard to European Patent No. 1169038 (the ‘038 patent), the Composition of Matter patent covering dasatinib, the active ingredient in Sprycel (Press release, Bristol-Myers Squibb, FEB 1, 2017, View Source [SID1234517615]). The EPO upheld a decision that found the patent to be invalid. Schedule your 30 min Free 1stOncology Demo! This decision does not impact our patents outside of the EU or other Sprycel-related patents.
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
BMS has a long-standing heritage in oncology. Sprycel will continue to be a significant asset in our broad oncology portfolio and an important treatment option for patients living with chronic myeloid leukemia (CML).
U.S. FDA-APPROVED INDICATIONS FOR SPRYCEL (dasatinib)
SPRYCEL (dasatinib) is indicated for the treatment of adults with:
Newly diagnosed adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.
Chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib.
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy.
IMPORTANT SAFETY INFORMATION
Myelosuppression:
Treatment with SPRYCEL is associated with severe (NCI CTC Grade 3/4) thrombocytopenia, neutropenia, and anemia, which occur earlier and more frequently in patients with advanced phase CML or Ph+ ALL than in patients with chronic phase CML. Myelosuppression was reported in patients with normal baseline laboratory values as well as in patients with pre-existing laboratory abnormalities.
In patients with chronic phase CML, perform complete blood counts (CBCs) every 2 weeks for 12 weeks, then every 3 months thereafter, or as clinically indicated
In patients with advanced phase CML or Ph+ ALL, perform CBCs weekly for the first 2 months and then monthly thereafter, or as clinically indicated
Myelosuppression is generally reversible and usually managed by withholding SPRYCEL temporarily and/or dose reduction
In clinical studies, myelosuppression may have also been managed by discontinuation of study therapy
Hematopoietic growth factor has been used in patients with resistant myelosuppression
Bleeding-Related Events:
SPRYCEL caused thrombocytopenia in human subjects. In addition, dasatinib caused platelet dysfunction in vitro. In all CML or Ph+ ALL clinical studies, ≥grade 3 central nervous system (CNS) hemorrhages, including fatalities, occurred in <1% of patients receiving SPRYCEL. Grade 3 or greater gastrointestinal hemorrhage, including fatalities, occurred in 4% of patients and generally required treatment interruptions and transfusions. Other cases of ≥grade 3 hemorrhage occurred in 2% of patients.
Most bleeding events in clinical studies were associated with severe thrombocytopenia
Concomitant medications that inhibit platelet function or anticoagulants may increase the risk of hemorrhage
Fluid Retention:
SPRYCEL may cause fluid retention. After 5 years of follow-up in the randomized newly diagnosed chronic phase CML study (n=258), grade 3/4 fluid retention was reported in 5% of patients, including 3% of patients with grade 3/4 pleural effusion. In patients with newly diagnosed or imatinib resistant or intolerant chronic phase CML, grade 3/4 fluid retention occurred in 6% of patients treated with SPRYCEL at the recommended dose (n=548). In patients with advanced phase CML or Ph+ ALL treated with SPRYCEL at the recommended dose (n=304), grade 3/4 fluid retention was reported in 8% of patients, including grade 3/4 pleural effusion reported in 7% of patients.
Patients who develop symptoms of pleural effusion or other fluid retention, such as new or worsened dyspnea on exertion or at rest, pleuritic chest pain, or dry cough should be evaluated promptly with a chest x-ray or additional diagnostic imaging as appropriate
Fluid retention events were typically managed by supportive care measures that may include diuretics or short courses of steroids
Severe pleural effusion may require thoracentesis and oxygen therapy
Consider dose reduction or treatment interruption
Cardiovascular Events:
After 5 years of follow-up in the randomized newly diagnosed chronic phase CML trial (n=258), the following cardiac adverse events occurred:
Cardiac ischemic events (3.9% dasatinib vs 1.6% imatinib), cardiac related fluid retention (8.5% dasatinib vs 3.9% imatinib), and conduction system abnormalities, most commonly arrhythmia and palpitations (7.0% dasatinib vs 5.0% imatinib). Two cases (0.8%) of peripheral arterial occlusive disease occurred with imatinib and 2 (0.8%) transient ischemic attacks occurred with dasatinib
Monitor patients for signs or symptoms consistent with cardiac dysfunction and treat appropriately.
Pulmonary Arterial Hypertension (PAH):
SPRYCEL may increase the risk of developing PAH, which may occur any time after initiation, including after more than 1 year of treatment. Manifestations include dyspnea, fatigue, hypoxia, and fluid retention. PAH may be reversible on discontinuation of SPRYCEL.
Evaluate patients for signs and symptoms of underlying cardiopulmonary disease prior to initiating SPRYCEL and during treatment. If PAH is confirmed, SPRYCEL should be permanently discontinued
QT Prolongation:
In vitro data suggest that dasatinib has the potential to prolong cardiac ventricular repolarization (QT interval).
In clinical trials of patients treated with SPRYCEL at all doses (n=2440), 16 patients (<1%) had QTc prolongation reported as an adverse reaction. Twenty-two patients (1%) experienced a QTcF >500 ms
In 865 patients with leukemia treated with SPRYCEL in five Phase 2 single-arm studies, the maximum mean changes in QTcF (90% upper bound CI) from baseline ranged from 7.0 to 13.4 ms
SPRYCEL may increase the risk of prolongation of QTc in patients including those with hypokalemia or hypomagnesemia, patients with congenital long QT syndrome, patients taking antiarrhythmic medicines or other medicinal products that lead to QT prolongation, and cumulative high-dose anthracycline therapy
Correct hypokalemia or hypomagnesemia prior to and during SPRYCEL administration
Severe Dermatologic Reactions:
Cases of severe mucocutaneous dermatologic reactions, including Stevens-Johnson syndrome and erythema multiforme, have been reported in patients treated with SPRYCEL.
Discontinue permanently in patients who experience a severe mucocutaneous reaction during treatment if no other etiology can be identified
Tumor Lysis Syndrome (TLS):
TLS has been reported in patients with resistance to prior imatinib therapy, primarily in advanced phase disease.
Due to potential for TLS, maintain adequate hydration, correct uric acid levels prior to initiating therapy with SPRYCEL, and monitor electrolyte levels
Patients with advanced stage disease and/or high tumor burden may be at increased risk and should be monitored more frequently
Embryo-Fetal Toxicity:
Based on limited human data, SPRYCEL can cause fetal harm when administered to a pregnant woman. Hydrops fetalis, fetal leukopenia and fetal thrombocytopenia have been reported with maternal exposure to SPRYCEL. Transplacental transfer of dasatinib has been measured in fetal plasma and amniotic fluid at concentrations comparable to those in maternal plasma.
Advise females of reproductive potential to avoid pregnancy, which may include the use of effective contraception, during treatment with SPRYCEL and for 30 days after the final dose
Lactation:
No data are available regarding the presence of dasatinib in human milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production. However, dasatinib is present in the milk of lactating rats.
Because of the potential for serious adverse reactions in nursing infants from SPRYCEL, breastfeeding is not recommended during treatment with SPRYCEL and for 2 weeks after the final dose
Drug Interactions:
SPRYCEL is a CYP3A4 substrate and a weak time-dependent inhibitor of CYP3A4.
Drugs that may increase SPRYCEL plasma concentrations are:
CYP3A4 inhibitors: Concomitant use of SPRYCEL and drugs that inhibit CYP3A4 should be avoided. If administration of a potent CYP3A4 inhibitor cannot be avoided, close monitoring for toxicity and a SPRYCEL dose reduction should be considered
Strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole). If SPRYCEL must be administered with a strong CYP3A4 inhibitor, a dose decrease or temporary discontinuation should be considered
Grapefruit juice may also increase plasma concentrations of SPRYCEL and should be avoided
Drugs that may decrease SPRYCEL plasma concentrations are:
CYP3A4 inducers: If SPRYCEL must be administered with a CYP3A4 inducer, a dose increase in SPRYCEL should be considered
Strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital) should be avoided. Alternative agents with less enzyme induction potential should be considered. If the dose of SPRYCEL is increased, the patient should be monitored carefully for toxicity
St John’s Wort may decrease SPRYCEL plasma concentrations unpredictably and should be avoided
Antacids may decrease SPRYCEL drug levels. Simultaneous administration of SPRYCEL and antacids should be avoided. If antacid therapy is needed, the antacid dose should be administered at least 2 hours prior to or 2 hours after the dose of SPRYCEL
H 2 antagonists/proton pump inhibitors (eg, famotidine and omeprazole): Long-term suppression of gastric acid secretion by use of H2 antagonists or proton pump inhibitors is likely to reduce SPRYCEL exposure. Therefore, concomitant use of H2 antagonists or proton pump inhibitors with SPRYCEL is not recommended
Drugs that may have their plasma concentration altered by SPRYCEL are:
CYP3A4 substrates (eg, simvastatin) with a narrow therapeutic index should be administered with caution in patients receiving SPRYCEL
Adverse Reactions:
The safety data reflects exposure to SPRYCEL at all doses tested in clinical studies including 324 patients with newly diagnosed chronic phase CML and 2388 patients with imatinib resistant or intolerant chronic or advanced phase CML or Ph+ ALL.
The median duration of therapy in all 2712 SPRYCEL-treated patients was 19.2 months (range 0–93.2 months). Median duration of therapy in:
1618 patients with chronic phase CML was 29 months (range 0–92.9 months)
Median duration for 324 patients in the newly diagnosed chronic phase CML trial was approximately 60 months
1094 patients with advanced phase CML or Ph+ ALL was 6.2 months (range 0–93.2 months)
In the newly diagnosed chronic phase CML trial, after a minimum of 60 months of follow-up, the cumulative discontinuation rate for 258 patients was 39%.
In the overall population of 2712 SPRYCEL-treated patients, 88% of patients experienced adverse reactions at some time and 19% experienced adverse reactions leading to treatment discontinuation.
Among the 1618 SPRYCEL-treated patients with chronic phase CML, drug-related adverse events leading to discontinuation were reported in 329 (20.3%) patients.
In the newly diagnosed chronic phase CML trial, drug was discontinued for adverse reactions in 16% of SPRYCEL-treated patients with a minimum of 60 months of follow-up
Among the 1094 SPRYCEL-treated patients with advanced phase CML or Ph+ ALL, drug-related adverse events leading to discontinuation were reported in 191 (17.5%) patients.
Patients ≥65 years are more likely to experience the commonly reported adverse reactions of fatigue, pleural effusion, diarrhea, dyspnea, cough, lower gastrointestinal hemorrhage, and appetite disturbance, and more likely to experience the less frequently reported adverse reactions of abdominal distention, dizziness, pericardial effusion, congestive heart failure, hypertension, pulmonary edema and weight decrease, and should be monitored closely.
In newly diagnosed chronic phase CML patients:
Drug-related serious adverse events (SAEs) were reported for 16.7% of SPRYCEL-treated patients. Serious adverse reactions reported in ≥5% of patients included pleural effusion (5%)
The most common adverse reactions (≥15%) included myelosuppression, fluid retention, and diarrhea
Grade 3/4 laboratory abnormalities included neutropenia (29%), thrombocytopenia (22%), anemia (13%), hypophosphatemia (7%), hypocalcemia (4%), elevated bilirubin (1%), and elevated creatinine (1%)
In patients resistant or intolerant to prior imatinib therapy:
Drug-related SAEs were reported for 26.1% of SPRYCEL-treated patients treated at the recommended dose of 100 mg once daily in the randomized dose-optimization trial of patients with chronic phase CML resistant or intolerant to prior imatinib therapy. Serious adverse reactions reported in ≥5% of patients included pleural effusion (10%)
The most common adverse reactions (≥15%) included myelosuppression, fluid retention events, diarrhea, headache, fatigue, dyspnea, skin rash, nausea, hemorrhage and musculoskeletal pain
Grade 3/4 hematologic laboratory abnormalities in chronic phase CML patients resistant or intolerant to prior imatinib therapy who received SPRYCEL 100 mg once daily with a minimum follow up of 60 months included neutropenia (36%), thrombocytopenia (24%), and anemia (13%). Other grade 3/4 laboratory abnormalities included: hypophosphatemia (10%), and hypokalemia (2%)
Among chronic phase CML patients with resistance or intolerance to prior imatinib therapy, cumulative grade 3/4 cytopenias were similar at 2 and 5 years including: neutropenia (36% vs 36%), thrombocytopenia (23% vs 24%), and anemia (13% vs 13%)
Grade 3/4 elevations of transaminases or bilirubin and Grade 3/4 hypocalcemia, hypokalemia, and hypophosphatemia were reported in patients with all phases of CML
Elevations in transaminases or bilirubin were usually managed with dose reduction or interruption
Patients developing Grade 3/4 hypocalcemia during the course of SPRYCEL therapy often had recovery with oral calcium supplementation
Clovis Oncology and Strata Oncology Announce Collaboration to Accelerate Enrollment in Rucaparib Prostate Cancer Development Program
On February 1, 2017 Clovis Oncology, Inc. (NASDAQ: CLVS) and Strata Oncology, Inc. reported an agreement to accelerate patient identification and enrollment for Clovis’ ongoing TRITON (Trial of Rucaparib in Prostate Indications) clinical trial program, which includes Phase 2 and Phase 3 clinical trials of rucaparib in metastatic castration-resistant prostate cancer, both of which are open for enrollment (Press release, Clovis Oncology, FEB 1, 2017, View Source [SID1234517614]). Schedule your 30 min Free 1stOncology Demo! Rucaparib is an oral inhibitor of poly ADP-ribose polymerase (PARP), approved in the U.S. in 2016 as Rubraca (rucaparib) as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer, who have been treated with two or more chemotherapies, and selected for therapy by an FDA-approved companion diagnostic. Emerging data suggest PARP inhibition may also provide activity in the treatment of metastatic prostate cancers harboring deleterious mutations in BRCA1/2 and ATM or other human genes associated with DNA damage repair. These mutations may be germline (inherited) or somatic (acquired).
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Strata Oncology is conducting the Strata Trial, an observational study that provides next-generation sequencing at no cost to all advanced cancer patients at its affiliated cancer centers and hospitals. Strata then refers patients with selected mutations to physicians involved in its pharmaceutical partners’ targeted clinical trials. Strata seeks to fulfill the promise of precision medicine by improving the number of patients identified with specific mutations appropriate for ongoing clinical trials.
Under the terms of the agreement, Strata will exclusively refer BRCA and ATM-mutated advanced prostate cancer patients for consideration of enrollment to Clovis’ TRITON2 and TRITON3 clinical trials of rucaparib. The Strata Trial is available at an expanding network of select cancer centers and hospitals nationwide.
"We’re delighted to work with Clovis Oncology in advancing development of their highly promising drug rucaparib for prostate cancer patients," said Dan Rhodes, Ph.D., CEO of Strata Oncology. "We are confident that we will identify a number of mutant BRCA and ATM prostate cancer patients through the Strata Trial, and accelerate enrollment in the TRITON2 and TRITON3 clinical trials."
"Following rucaparib’s initial U.S. approval in ovarian cancer, we are committed to rapidly enrolling additional trials and expanding rucaparib development into broader indications, including prostate," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "Through our work with Strata, we seek to address the significant challenge of identifying and enrolling the right patients – in this case, patients with advanced prostate cancer who possess mutations of BRCA and/or ATM – in support of advancing our precision medicine clinical trials and potentially providing rucaparib to a broader population of patients who may benefit."
Pipeline Review Check
Phase 1
Phase 2
Phase 3
Application
Therapeutic
area
Cardiovascular-
Metabolics
Oncology
Others
Edoxaban (JP)
(DU-176b / AF / FXa inhibitor)
Prasugrel (JP)
(CS-747 / Ischemic stroke / Anti-
platelet agent)
Esaxerenone (JP)
(CS-3150 / Hypertension /
MR antagonist)
Edoxaban (ASCA etc.)
(DU-176b / AF / FXa inhibitor)
Edoxaban (ASCA etc.)
(DU-176b / VTE / FXa inhibitor)
Tivantinib (US/EU)
(ARQ 197 / HCC / MET inhibitor)
Denosumab (JP)
(AMG 162 / Breast cancer adjuvant /
Anti-RANKL antibody)
Nimotuzumab (JP)
(DE-766 / Gastric cancer / Anti-EGFR
antibody)
Vemurafenib (US/EU)
(PLX4032 / Melanoma Adjuvant / BRAF
inhibitor)
Quizartinib (US/EU/Asia)
(AC220 / AML-2
nd
/ FLT3-ITD inhibitor)
Quizartinib (US/EU/Asia)
(AC220 / AML-1
st
/ FLT3-ITD inhibitor)
Pexidartinib (US/EU)
(PLX3397 / TGCT / CSF-1R/KIT/FLT3-ITD
inhibitor)
Laninamivir (US/EU)
(CS-8958 / Anti-influenza /
out-licensing with Biota)
Mirogabalin (US/EU)
(DS-5565 / Fibromyalgia / α2δ ligand)
Mirogabalin (JP/Asia)
(DS-5565 / DPNP/ α2δ ligand)
Mirogabalin (JP/Asia)
(DS-5565 / PHN / α2δ ligand)
Hydromorphone (JP)
(DS-7113 / Cancer pain / Opioid μ-
receptor regulator)
CHS-0214 (JP)
(Etanercept BS / Rheumatoid
arthritis / TNFα inhibitor)
VN-0105 (JP)
(DPT-IPV / Hib vaccine)
Laninamivir (JP)
(CS-8958 / Anti-influenza / nebulizer)
Esaxerenone (JP)
(CS-3150 / DM nephropathy / MR
antagonist)
DS-8500 (JP/US)
(Diabetes / GPR119 agonist)
Patritumab (EU)
(U3-1287 / Anti-HER3 antibody)
Pexidartinib (US)
(PLX3397 / CSF-1R/KIT/FLT3-ITD
inhibitor)
DS-1647 (JP)
(Glioblastoma / G47Δ virus)
DS-1040
(Acute ischemic stroke / TAFIa inhibitor)
DS-2330
(Hyperphosphatemia)
DS-9231/TS23
(Thrombosis / α2-PI inactivating antibody)
DS-9001
(Dyslipidemia / Anti-PCSK9 Anticalin-Albumod)
DS-3032 (US/JP)
(MDM2 inhibitor)
PLX7486 (US)
(FMS / TRK inhibitor)
PLX8394 (US)
(BRAF inhibitor)
DS-6051 (US/JP)
(NTRK/ROS1 inhibitor)
PLX9486 (US)
(KIT inhibitor)
DS-3201 (JP)
(EZH1/2 inhibitor)
PLX73086 (US)
(CSF-1R inhibitor)
PLX51107 (US)
(BRD4 inhibitor)
DS-1971
(Chronic pain)
DS-1501
(Osteoporosis / Anti-Siglec-15 antibody)
DS-7080 (US)
(AMD / Angiogenesis inhibitor)
DS-2969
(
Clostridium difficile
infection
/GyrB inhibitor)
DS-5141 (JP)
(DMD / ENA oligonucleotide)
VN-0102/JVC-001 (JP)
(MMR vaccine)
Hydromorphone (JP)
(DS-7113 / Cancer pain / Opioid μ-
receptor agonist)
CL-108 (US)
(Acute pain / Opioid μ-receptor
agonist)
Intradermal Seasonal
Influenza Vaccine (JP)
(VN-100 / prefilled i.d. vaccine for
seasonal flu)
VN-0107/MEDI3250 (JP)
(Nasal spray flu vaccine)
Denosumab (JP)
(AMG 162 / Rheumatoid arthritis /
Anti-RANKL antibody)
Major R&D Pipeline
DS-8895 (JP)
(Anti-EPHA2 antibody)
DS-8273 (US)
(Anti-DR5 antibody)
DS-5573 (JP)
(Anti-B7-H3 antibody)
DS-8201 (JP/US)
(Anti-HER2 ADC)
U3-1784 (EU)
(Anti-FGFR4 antibody)
DS-1123 (JP)
(Anti-FGFR2 antibody)
U3-1402 (JP)
(Anti-HER3 ADC)
As of January 2017
Red: Major changes after the FY2016 Q2 financial announcement on October 31, 2016
11. Major R&D Pipeline (Innovative pharmaceuticals
）
◆
Oncology (Late-stage pipeline products)
Generic Name/Project Code Number
(Brand Name)
Class
Target indication
Region Stage
Dosage
Form
Partner
Target FY for
approval/launch
Anti-RANKL antibody
Breast cancer adjuvant
JP
P3 Injection
Amgen
2020
BRAF inhibitor
Melanoma adjuvant
US/EU
P3
Oral
–
–
MET inhibitor
Hepatocellular cancer
US/EU
P3
Oral
ArQule, Inc.
2018
US/EU/Asia P3
2018
US/EU/Asia P3
2021-
JP
P1
–
Tenosynovial Giant Cell Tumor (TGCT)
US/EU
P3
2019
Solid tumor
Asia
P1
–
Glioblastoma
US
P2
–
c-KIT Melanoma
Asia
P1/2
–
Melanoma, solid tumor
US
P1/2
Merck & Co., Inc.
–
Anti-EGFR antibody
Gastric cancer
JP
P3 Injection InnoClMAb Pte Ltd
2020
Anti-HER3 antibody
Head & neck cancer
EU
P2 Injection
–
–
Oncolytic HSV-1
Glioblastoma
JP
P2 Injection
ActiVec Inc.
–
Remarks
Denosumab/AMG 162
Ranmark (JP)
Additional indication
The fully human monoclonal antibody to target RANK Ligand, an essential mediator of osteoclast formation.
Vemurafenib/PLX4032
Zelboraf
Additional indication. Licensee Roche is conducting the
study. Submission in 2017 is planned.
The molecular-targeted agent to inhibit BRAF V600E mutation.
Tivantinib/ARQ 197
HCC with MET high patients
The molecular-targeted agent to inhibit HGF(hepatocyte growth factor) receptor, MET which has multiple roles in intracellular signal transductions such as cancer cell proliferation, angiogenesis, invasion, and apoptosis
induction.
Nimotuzumab/DE-766
Patritumab/U3-1287
Pexidartinib/PLX3397
CSF-1R/KIT/FLT3-ITD inhibitor
Oral
–
Quizartinib/AC220
FLT3-ITD inhibitor
Acute myeloid leukemia
Oral
–
Relapsed and refractory AML patients
Newly diagnosed AML patients
Kinase inhibitor against a receptor-type tyrosine kinase, FLT3. Therapeutic effect for patients with acute myeloid leukemia harboring FLT3-ITD mutation is expected.
DS-1647(G47
D
)
Received SAKIGAKE Designation from MHLW
Investigator Initiated Study is on-going
The third generation oncolytic herpes simplex virus type 1(HSV-1), ghenetically-engineered to restrict virus replication to tumor cells. This oncolytic virus therapy is expected equal or better safety and better efficacy profile
compare to existing oncolytic virus.
Underline: change after FY2016 Q2 Financial Announcement in October 2016
As of January 2017
The humanized monoclonal antibody to target Epidermal Growth Factor Receptor(EGFR). This antibody is expected to be a best in class EGFR, safety against the skin toxicity and the efficacy comparable to the other
antibodies.
The fully human monoclonal antibody to target HER3, one of the Epidermal Growth Factor Receptor (EGFR) family of proteins. HER 3 is overexpressed in many tumors of epithelial origin and HER2/HER3 dimers and
EGFR/HER3 dimers are expected more potent to induce tumor cell proliferation than homodimers of HER2 or EGFR.
Including pigmented villonodular synovitis
Including TGCT
Combination with pembrolizumab in collaboration with
Merck
The molecular-targeted agent to inhibit CSF-1R, KIT and FLT3-ITD. This agent is expected to reduce tumor cell proliferation and expansion of metastases.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Humana Issues Positive Coverage Decision for NanoString’s Prosigna® Breast Cancer Assay
On January 31, 2017 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, reported that Humana has issued a positive coverage decision for the Prosigna Breast Cancer Gene Signature Assay (Press release, NanoString Technologies, JAN 31, 2017, View Source [SID1234517618]). Humana and its more than 13 million members join other payors now covering Prosigna, collectively representing more than 175 million covered lives throughout the United States.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
This positive coverage decision is in line with updated ASCO (Free ASCO Whitepaper) guidelines released in February of 2016, wherein Prosigna is considered medically necessary to assess the necessity of adjuvant chemotherapy in ER-positive, HER2-negative, node-negative breast cancer patients, when adjuvant chemotherapy is not precluded due to any other factor.
"Coverage by Humana is another important milestone in making our Prosigna test available to all indicated patients," said Brad Gray, president and chief executive officer of NanoString Technologies. "Our team has done an outstanding job of working with both national and regional payors to ensure that their patients have access to this state-of-the-art test."
The updated healthcare policy for Humana, which now includes the Prosigna Assay, is available on its website:
View Source;searchtype=freetext&policyType=both
About the Prosigna Breast Cancer Prognostic Gene Signature Assay and nCounter Dx Analysis System
The Prosigna Assay provides a risk category and numerical score for assessment of the risk of distant recurrence of disease at 10 years in postmenopausal women with node-negative (Stage I or II) or node-positive (Stage II), hormone receptor-positive (HR+) breast cancer. Based on the PAM50 gene signature initially discovered by Charles Perou, Ph.D. and colleagues, the Prosigna Assay is an in vitro diagnostic tool that utilizes gene expression data weighted together with clinical variables to generate a risk category and numerical score to assess a patient’s risk of distant recurrence of disease. The Prosigna Assay measures gene expression levels of RNA extracted from formalin-fixed paraffin embedded (FFPE) breast tumor tissue previously diagnosed as invasive breast carcinoma.
The Prosigna Assay requires minimal hands-on time and runs on NanoString’s proprietary nCounter Dx Analysis System, which offers a reproducible and cost-effective way to profile many genes simultaneously with high sensitivity and precision.
The nCounter Dx Analysis System is a highly automated and easy-to-use platform that utilizes a novel digital barcoding chemistry to deliver high precision multiplexed assays. The system is available in the multi-mode FLEX configuration, which is designed to meet the needs of high-complexity clinical laboratories seeking a single platform with the flexibility to run the Prosigna Breast Cancer Assay and, when operated in the "Life Sciences" mode, process translational research experiments and multiplexed assays developed by the laboratory.
In the United States, the Prosigna Assay is 510(k) cleared for use on the nCounter Dx Analysis System, and is available for diagnostic use when ordered by a physician. The Prosigna Assay has been CE-marked and is available for use by healthcare professionals in the European Union and other countries that recognize the CE Mark, as well as Canada, Israel, Australia, New Zealand and Hong Kong. In the U.S., the Prosigna Assay is indicated in female breast cancer patients who have undergone surgery in conjunction with locoregional treatment consistent with standard of care, either as:
(1) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-negative, Stage I or II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors or (2) a prognostic indicator for distant recurrence-free survival at 10 years in postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-positive (1-3 nodes), Stage II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors. The device is not intended for patients with four or more positive nodes.
For more information, please visit www.prosigna.com.
Thermo Fisher Scientific Reports Fourth Quarter and Full Year 2016 Results
On January 31, 2017 Thermo Fisher Scientific Inc. (NYSE: TMO), the world leader in serving science, reported its financial results for the fourth quarter and full year ended December 31, 2016 (Press release, Thermo Fisher Scientific, JAN 31, 2017, View Source [SID1234517606]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Fourth Quarter and Full Year 2016 Highlights
Fourth quarter revenue increased 6% to $4.95 billion.
Full year revenue grew 8% to $18.27 billion.
Fourth quarter GAAP diluted earnings per share (EPS) increased 6% to $1.59.
Fourth quarter adjusted EPS grew 14% to $2.41.
Full year GAAP diluted EPS increased 3% to $5.09.
Full year adjusted EPS grew 12% to $8.27.
Invested more than $750 million in R&D in 2016, and launched significant new products, including Q Exactive BioPharma mass spectrometry and Integrion chromatography systems, TSX laboratory freezers, Ion Torrent cancer assays, and new tests for drugs-of-abuse and autoimmune disease.
Strengthened capabilities in Shanghai, Seoul and Singapore during the year to build on industry-leading presence in Asia-Pacific and emerging markets and continued to deliver strong growth in the region, led by outstanding performance in China.
Deployed approximately $7 billion of capital in 2016, with $5.5 billion spent on strategic acquisitions, including FEI Company and Affymetrix, and $1.5 billion returned to shareholders through a combination of stock buybacks and dividends.
Adjusted EPS, adjusted operating income, adjusted operating margin and free cash flow are non-GAAP measures that exclude certain items detailed later in this press release under the heading "Use of Non-GAAP Financial Measures."
"I’m pleased to report that we achieved the goals we laid out for 2016, and successfully executed our strategy to deliver another excellent year," said Marc N. Casper, president and chief executive officer of Thermo Fisher Scientific.
"We effectively deployed the largest R&D budget in our industry, and launched new high-impact products across all of our technology platforms. In Asia-Pacific and emerging markets, we leveraged our industry-leading scale to drive strong growth, especially in China, where we’re capturing opportunities aligned with the new five-year plan.
"We also continued to successfully execute our capital deployment strategy to create value for our shareholders. I’m really excited about our acquisition of FEI – the third largest in our history – and look forward to the opportunities we have to leverage these complementary technologies to drive growth.
"To sum it up, with a strong 2016 behind us, we’re positioned for another great year ahead."
Fourth Quarter 2016
As previously communicated, the company’s 2016 fiscal calendar had four fewer selling days in the fourth quarter versus the fourth quarter of 2015. Consequently, revenue and organic growth results in the 2016 quarter were negatively affected by the fewer days, and operating margin benefited due to fewer days of costs. Revenue for the quarter grew 6% to $4.95 billion in 2016, versus $4.65 billion in 2015. Organic revenue growth was essentially flat; acquisitions increased revenue by 8% and currency translation reduced revenue by 1%.
GAAP Earnings Results
GAAP diluted EPS in the fourth quarter increased to $1.59, versus $1.50 in the same quarter last year. GAAP operating income for the fourth quarter of 2016 grew to $753 million, compared with $690 million in the fourth quarter of 2015. GAAP operating margin increased to 15.2%, compared with 14.8% in the fourth quarter of 2015.
Non-GAAP Earnings Results
Adjusted EPS in the fourth quarter of 2016 rose 14% to $2.41, versus $2.12 in the fourth quarter of 2015. Adjusted operating income for the fourth quarter of 2016 grew 14% compared with the year-ago quarter. Adjusted operating margin expanded 160 basis points to 24.8%, compared with 23.2% in the fourth quarter of 2015.
Full Year 2016
Revenue for the full year grew 8% to $18.27 billion in 2016, versus $16.97 billion in 2015. Organic revenue growth was 4%; acquisitions increased revenue by 4% and currency translation reduced revenue by 1%.
GAAP Earnings Results
GAAP diluted EPS for the full year increased to $5.09, versus $4.92 in 2015. GAAP operating income for 2016 grew to $2.45 billion, compared with $2.34 billion a year ago. GAAP operating margin was 13.4% in 2016, compared with 13.8% in 2015. GAAP operating results reflect acquisition-related charges in the 2016 period.
Non-GAAP Earnings Results
Adjusted EPS for the full year rose 12% to $8.27, versus $7.39 in 2015. Adjusted operating income for 2016 grew 10% compared with 2015, and adjusted operating margin expanded 60 basis points to 23.1%, compared with 22.5% a year ago.
Annual Guidance for 2017
The company will provide 2017 financial guidance on its earnings conference call this morning at 8:30 a.m. Eastern time.
Segment Results
Management uses adjusted operating results to monitor and evaluate performance of the company’s four business segments, as highlighted below. Since these results are used for this purpose, they are also considered to be prepared in accordance with GAAP.
Fourth quarter revenue results were negatively affected by the four fewer selling days in 2016 and fourth quarter operating margin benefited from fewer days of costs. Fourth quarter and full year results were negatively affected by the impact of foreign currency exchange rates. The impact of the fewer days in the fourth quarter and foreign exchange affects each of the segments to varying degrees.
Life Sciences Solutions Segment
In the fourth quarter of 2016, Life Sciences Solutions Segment revenue grew 10% to $1.34 billion, compared with revenue of $1.21 billion in the fourth quarter of 2015. Segment adjusted operating margin increased to 33.3%, versus 31.6% in the 2015 quarter.
For the full year 2016, Life Sciences Solutions Segment revenue rose 12% to $4.98 billion, compared with revenue of $4.44 billion in 2015. Segment adjusted operating margin increased to 30.4% in 2016, compared with 30.1% a year ago.
Analytical Instruments Segment
Analytical Instruments Segment revenue grew 32% to $1.22 billion in the fourth quarter of 2016, compared with revenue of $925 million in the fourth quarter of 2015. Segment adjusted operating margin increased to 24.5%, versus 22.1% in the 2015 quarter.
For the full year 2016, Analytical Instruments Segment revenue rose 14% to $3.67 billion, compared with revenue of $3.21 billion in 2015. Segment adjusted operating margin grew to 20.3%, versus 19.1% in 2015.
Specialty Diagnostics Segment
Specialty Diagnostics Segment revenue in the fourth quarter was $834 million in 2016, compared with revenue of $865 million in the fourth quarter of 2015. Segment adjusted operating margin increased to 27.2%, versus 26.2% in the 2015 quarter.
For the full year 2016, Specialty Diagnostics Segment revenue grew 3% to $3.34 billion, compared with revenue of $3.24 billion in 2015. Segment adjusted operating margin increased to 27.2%, versus 2015 results of 26.9%.
Laboratory Products and Services Segment
In the fourth quarter of 2016, Laboratory Products and Services Segment revenue was $1.76 billion, compared with revenue of $1.82 billion in the fourth quarter of 2015. Segment adjusted operating margin was 14.6%, versus 14.7% in the 2015 quarter.
For the full year 2016, Laboratory Products and Services Segment revenue grew 6% to $7.03 billion, compared with revenue of $6.66 billion in 2015. Segment adjusted operating margin was 15.0% in both periods.
Use of Non-GAAP Financial Measures
In addition to the financial measures prepared in accordance with generally accepted accounting principles (GAAP), we use certain non-GAAP financial measures, including adjusted EPS, adjusted operating income and adjusted operating margin, which exclude certain acquisition-related costs, including charges for the sale of inventories revalued at the date of acquisition and significant transaction costs; restructuring and other costs/income; and amortization of acquisition-related intangible assets. Adjusted EPS also excludes certain other gains and losses that are either isolated or cannot be expected to occur again with any regularity or predictability, tax provisions/benefits related to the previous items, benefits from tax credit carryforwards, the impact of significant tax audits or events and the results of discontinued operations. We exclude the above items because they are outside of our normal operations and/or, in certain cases, are difficult to forecast accurately for future periods. We also use a non-GAAP measure, free cash flow, which is operating cash flow, net of capital expenditures, and also excludes operating cash flows from discontinued operations to provide a view of the continuing operations’ ability to generate cash for use in acquisitions and other investing and financing activities. We believe that the use of non-GAAP measures helps investors to gain a better understanding of our core operating results and future prospects, consistent with how management measures and forecasts the company’s performance, especially when comparing such results to previous periods or forecasts.
For example:
We exclude costs and tax effects associated with restructuring activities, such as reducing overhead and consolidating facilities. We believe that the costs related to these restructuring activities are not indicative of our normal operating costs.
We exclude certain acquisition-related costs, including charges for the sale of inventories revalued at the date of acquisition and significant transaction costs. We exclude these costs because we do not believe they are indicative of our normal operating costs.
We exclude the expense and tax effects associated with the amortization of acquisition-related intangible assets because a significant portion of the purchase price for acquisitions may be allocated to intangible assets that have lives of 5 to 20 years. In 2017, based on acquisitions closed through the end of 2016, our adjusted EPS will exclude approximately $2.53 of expense for the amortization of acquisition-related intangible assets. Exclusion of the amortization expense allows comparisons of operating results that are consistent over time for both our newly acquired and long-held businesses and with both acquisitive and non-acquisitive peer companies.
We also exclude certain gains/losses and related tax effects, benefits from tax credit carryforwards and the impact of significant tax audits or events (such as the effect on deferred tax balances of enacted changes in tax rates), which are either isolated or cannot be expected to occur again with any predictability and that we believe are not indicative of our normal operating gains and losses. For example, we exclude gains/losses from items such as the sale of a business or real estate, gains or losses on significant litigation-related matters, gains on curtailments of pension plans, the early retirement of debt and discontinued operations.
We also report free cash flow, which is operating cash flow, net of capital expenditures, and also excludes operating cash flows from discontinued operations to provide a view of the continuing operations’ ability to generate cash for use in acquisitions and other investing and financing activities.
Thermo Fisher’s management uses these non-GAAP measures, in addition to GAAP financial measures, as the basis for measuring the company’s core operating performance and comparing such performance to that of prior periods and to the performance of our competitors. Such measures are also used by management in their financial and operating decision-making and for compensation purposes.
The non-GAAP financial measures of Thermo Fisher’s results of operations and cash flows included in this press release are not meant to be considered superior to or a substitute for Thermo Fisher’s results of operations prepared in accordance with GAAP. Reconciliations of such non-GAAP financial measures to the most directly comparable GAAP financial measures are set forth in the accompanying tables. Thermo Fisher does not provide GAAP financial measures on a forward-looking basis because we are unable to predict with reasonable certainty and without unreasonable effort items such as the timing and amount of future restructuring actions and acquisition-related charges as well as gains or losses from sales of real estate and businesses, the early retirement of debt and the outcome of legal proceedings. The timing and amount of these items are uncertain and could be material to Thermo Fisher’s results computed in accordance with GAAP.