On April 4, 2019 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that the U.S. Food and Drug Administration (FDA) has extended the review period for the New Drug Application (NDA) of quizartinib, an investigational FLT3 inhibitor, currently under Priority Review for the treatment of adult patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML) (Press release, Daiichi Sankyo, APR 4, 2019, View Source [SID1234535007]). The new Prescription Drug User Fee Act (PDUFA) action date is August 25, 2019.

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The FDA extended the action date by three months to allow time to review additional data submitted by Daiichi Sankyo in association with an FDA request.

"We look forward to continued dialogue with the FDA throughout the review process of quizartinib," said Arnaud Lesegretain, Vice President, Oncology Research and Development and Head, AML Franchise, Daiichi Sankyo. "We remain confident in the data supporting our NDA submission and are committed to bringing quizartinib forward as a potential treatment for relapsed or refractory FLT3-ITD AML, a particularly aggressive and difficult-to-treat subtype of AML, where patients need additional targeted treatment options."

About Quizartinib
Quizartinib, the lead investigational agent in the investigational AML Franchise of the Daiichi Sankyo Cancer Enterprise, is an oral selective type II FLT3 inhibitor currently under regulatory review with the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the Japan Ministry of Health, Labour and Welfare (MHLW) for the treatment of adult patients with relapsed/
refractory AML, which is FLT3-ITD positive.

Regulatory submissions in the U.S., EU and Japan are based on the results of the pivotal phase 3 QuANTUM-R study of quizartinib, which was the first randomized phase 3 study to show that a FLT3 inhibitor prolonged overall survival as an oral, single agent compared to chemotherapy in patients with relapsed/refractory FLT3-ITD AML. Topline results of the phase 3 QuANTUM-R study were presented during the plenary program at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in June 2018, and comprehensive analyses were presented during an oral presentation at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in December 2018.

In the QuANTUM-R study, the median treatment duration with quizartinib was 4 cycles of 28 days each versus 1 cycle in the salvage chemotherapy arm. Incidence of treatment-emergent adverse events was comparable between patients who received single agent quizartinib and those who received salvage chemotherapy. The most common adverse drug reactions (>30 percent, any Grade) in patients treated with quizartinib included infections, bleeding, nausea, asthenic conditions, pyrexia, febrile neutropenia and vomiting, and the most common Grade ≥ 3 adverse drug reactions (>20 percent) were infection and febrile neutropenia. The most common laboratory adverse reactions (incidence >50 percent) were decreased white blood cell count, decreased lymphocyte count, decreased hemoglobin, decreased neutrophil count and decreased platelet count. The safety profile observed in QuANTUM-R appears consistent with that observed at similar doses in the quizartinib clinical development program.

Quizartinib also is in phase 3 development for newly-diagnosed FLT3-ITD AML(QuANTUM-First) in the U.S., EU and Japan and in phase 1 development in combination with an investigational MDM2 inhibitor, milademetan, for relapsed/refractory FLT3-ITD AML and newly-diagnosed FLT3-ITD AML unfit for intensive chemotherapy in the U.S., EU and Japan.

Quizartinib is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About FLT3-ITD Acute Myeloid Leukemia
AML is an aggressive blood and bone marrow cancer that causes uncontrolled growth and accumulation of malignant white blood cells that fail to function normally and interfere with the production of normal blood cells. In the U.S. this year, it is estimated that there will be more than 19,000 new diagnoses of AML and more than 10,000 deaths from AML. The five-year survival rate of AML reported from 2005 to 2011 was approximately 26 percent, which was the lowest of all leukemias.1

FLT3 gene mutations are one of the most common genetic abnormalities in AML. FLT3-ITD is the most common FLT3 mutation, affecting approximately one in four patients with AML. , , , FLT3-ITD is a driver mutation that presents with high leukemic burden and has poor prognosis and a significant impact on disease management for patients with AML.5,

Patients with FLT3-ITD AML have a worse overall prognosis, including an increased incidence of relapse, an increased risk of death following relapse, and a higher likelihood of relapse following hematopoietic stem cell transplantation, as compared to those without this mutation. ,

About Daiichi Sankyo Cancer Enterprise
The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by three pillars including our investigational Antibody Drug Conjugate Franchise, Acute Myeloid Leukemia Franchise and Breakthrough Science, we aim to deliver seven distinct new molecular entities over eight years during 2018 to 2025. Our powerful research engines include two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. Compounds in pivotal stage development include: [fam-] trastuzumab deruxtecan, an antibody drug conjugate (ADC) for HER2 expressing breast, gastric and other cancers; quizartinib, an oral selective FLT3 inhibitor, for newly-diagnosed and relapsed/refractory FLT3-ITD acute myeloid leukemia (AML); and pexidartinib, an oral CSF1R inhibitor, for tenosynovial giant cell tumor (TGCT). For more information, please visit: www.DSCancerEnterprise.com

On April 4, 2019 CStone Pharmaceuticals ("CStone"; HKEX:2616) reported a poster of pre-clinical data of CS1003 at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, CStone Pharmaceauticals, APR 4, 2019, View Source [SID1234535024]).

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CS1003 is a humanized IgG4 PD-1 monoclonal antibody designed to block the interaction of PD-1 with its ligands PD-L1 and PD-L2 for the immunotherapy of multiple tumor types. In contrast with other PD-1 antibodies, CS1003 recognizes both human and murine PD-1, providing a unique competitive advantage during efficacy testing in syngeneic mouse tumor models.

According to the pre-clinical result presented for the first time, CS1003 can specifically bind to human, mouse and cynomolgus monkey PD-1 and block the binding of PD-1 to PD-L1 and PD-L2; as a result, CS1003 promotes the proliferation and cytokine release of CD4+ T cells in vitro, and inhibites tumor progression in both CloudmanS91 mouse melanoma syngeneic model and MC38-huPD-L1 colon cancer engrafted in hu-PD-1 knock-in mouse model in vivo. The pharmacokinetic (PK) study in cynomolgus monkeys following single intravenous administration showed the exposure of CS1003 increased proportionally with dose levels and the PK properties were linear over 2-18 mg/kg. CS1003 demonstrated a favorable safety profile with the highest non-severely toxic dose (HNSTD) at 100 mg/kg.

CStone is currently conducting a Phase I clinical trial in China and Australia, and received Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (‘FDA’) for CS1003 in October 2018.

"CS1003 is a differentiated anti-PD-1 monoclonal antibody which allows us to quickly evaluate efficacy for combination therapies in animal models at the preclinical stage, and better predict the safety and efficacy of clinical trials," CStone Chief Science Officer Dr. Jon Wang noted. "As one of CStone’s immune-oncology backbone drug candidates, we will leverage this unique advantage to explore and develop combination therapies with CS1003 for various solid tumors and hematological malignancies, with the aim of providing better treatment options to patients in China and globally. "

Clinical Status of CS1003

CStone is currently conducting a Phase I clinical trial in Australia to assess the safety and anti-tumor effects of CS1003 as a monotherapy in patients with advanced solid tumors. CStone received Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA) for CS1003 in October 2018 and will extend the Phase I study to the United States.

CS1003 was approved in June 2018 by the China National Medical Product Administration (NMPA) to start clinical research, and a Phase I bridging clinical study was initiated in November 2018 for patients to start clinical research with advanced solid tumors and lymphomas.

On April 4, 2019 Pfizer (NYSE:PFE) reported that the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) to expand the indications for IBRANCE (palbociclib) in combination with an aromatase inhibitor or fulvestrant to include men with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer (Press release, Pfizer, APR 4, 2019, View Source [SID1234534992]). The approval is based on data from electronic health records and postmarketing reports of the real-world use of IBRANCE in male patients sourced from three databases: IQVIA Insurance database, Flatiron Health Breast Cancer database and the Pfizer global safety database.

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"With this approval, we are now able to offer IBRANCE to the underserved male breast cancer community and provide more patients with HR+, HER2- metastatic breast cancer the opportunity to access an innovative medicine," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "We appreciate that our partnership with the FDA has allowed us to take a significant step forward in the use of real-world data to bring medicines to patients who are most in need."

IBRANCE is now approved for adult patients with HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women or in men; or with fulvestrant in patients with disease progression following endocrine therapy. With today’s approval, IBRANCE is the first and only CDK 4/6 inhibitor indicated in combination with an aromatase inhibitor for the first-line treatment of men with HR+, HER2- metastatic breast cancer in the U.S.

"Men with breast cancer have limited treatment options, making access to medicines such as IBRANCE critically important," said Bret Miller, founder of the Male Breast Cancer Coalition. "We applaud the use of real-world data, a new approach to drug review, to make IBRANCE available to certain men with metastatic breast cancer and help address an unmet need for these patients."

Real-world data is playing an increasingly important role in expanding the use of already approved innovative medicines.1 Due to the rarity of breast cancer in males, fewer clinical trials are conducted that include men resulting in fewer approved treatment options. In the U.S. in 2019, it is estimated that there will be 2,670 new cases of invasive breast cancer and about 500 deaths from metastatic breast cancer in males.2 The 21st Century Cures Act, enacted in 2016, was created to help accelerate medical product development, allowing new innovations and advances to become available to patients who need them faster and more efficiently.3 This law places additional focus on the use of real-world data to support regulatory decision-making.4

Detailed analysis of the use of IBRANCE in men with HR+, HER2- advanced or metastatic breast cancer will be presented at an upcoming medical meeting. Based on limited data from postmarketing reports and electronic health records, the safety profile for men treated with IBRANCE is consistent with the safety profile in women treated with IBRANCE.5

About IBRANCE (palbociclib) 125 mg capsules

IBRANCE is an oral inhibitor of CDKs 4 and 6,6 which are key regulators of the cell cycle that trigger cellular progression.7,8 In the U.S., IBRANCE is indicated for the treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women or in men; or with fulvestrant in patients with disease progression following endocrine therapy.

IBRANCE currently is approved in more than 90 countries and has been prescribed to more than 200,000 patients globally.

The full prescribing information for IBRANCE can be found here.

IMPORTANT IBRANCE (palbociclib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Neutropenia was the most frequently reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 15 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.

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 to consider sperm preservation before taking IBRANCE. 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 PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97% vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%), decreased platelets (63% vs 14%), increased aspartate aminotransferase (52% vs 34%), and increased alanine aminotransferase (43% vs 30%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were 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%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs 1%) and leukopenia (31% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), decreased platelets (62% vs 10%), increased aspartate aminotransferase (43% vs 48%), and increased alanine aminotransferase (36% vs 34%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg. 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.

For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of IBRANCE is 75 mg. The pharmacokinetics of IBRANCE have not been studied in patients requiring hemodialysis.

On April 4, 2019 GlycoMimetics, Inc. (Nasdaq: GLYC) reported that senior management will present corporate updates at two upcoming investor conferences in April (Press release, GlycoMimetics, APR 4, 2019, View Source [SID1234535009]). Details are as follows:

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HC WAINWRIGHT GLOBAL LIFE SCIENCES CONFERENCE
Who: Chief Financial Officer Brian Hahn
When: Tuesday, April 9 at 2:10 p.m. (GMT)
Where: London, UK

18TH ANNUAL NEEDHAM HEALTHCARE CONFERENCE
Who: Chief Executive Officer Rachel King
When: Wednesday, April 10 at 3:30 p.m. (ET)
Where: New York, NY

To access the live webcast and subsequent archived recordings for each of these presentations, please visit the GlycoMimetics website at www.glycomimetics.com.

On April 4, 2019 Quest Diagnostics Incorporated (NYSE: DGX), the world’s leading provider of diagnostic information services, reported that it will report first quarter 2019 results on Tuesday, April 23, 2019, before the market opens (Press release, Quest Diagnostics, APR 4, 2019, View Source [SID1234535027]). It will hold its quarterly conference call to discuss the results beginning at 8:30 a.m. Eastern Time on that day.

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The conference call can be accessed by dialing 888-455-0391 within the U.S. and Canada, or 773-756-0467 internationally, using the passcode: "Investor." The earnings release and live webcast will be posted on www.QuestDiagnostics.com/investor. The company suggests participants dial in approximately 10 minutes before the call.

A replay of the call may be accessed online at www.QuestDiagnostics.com/investor or by phone at 866-480-3547 for domestic callers or 203-369-1551 for international callers, no passcode is required. Telephone replays will be available from approximately 10:30 a.m. Eastern Time on April 23, 2019 until midnight Eastern Time on May 7, 2019.

Anyone listening to the call is encouraged to read the company’s periodic reports on file with the Securities and Exchange Commission, including the discussion of risk factors and historical results of operations and financial condition in those reports.