On November 21, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that the U.S. Food and Drug Administration (FDA) has accepted a New Drug Application (NDA) and granted Priority Review for quizartinib for the treatment of adult patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML) (Press release, Daiichi Sankyo, NOV 21, 2018, https://www.prnewswire.com/news-releases/fda-grants-priority-review-for-daiichi-sankyos-new-drug-application-for-flt3-inhibitor-quizartinib-for-treatment-of-patients-with-relapsedrefractory-flt3-itd-aml-300754221.html [SID1234531556]).

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A Priority Review designation is granted by the FDA to drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions when compared to standard applications. Under Priority Review, the FDA aims to take action on an application within six months as compared to 10 months under standard review. The FDA is expected to make a decision on approval by May 25, 2019.

The NDA is based on 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 new analyses will be presented during an oral presentation at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) on Monday, December 3.

"If approved, quizartinib has the potential to meaningfully advance treatment for patients with relapsed or refractory FLT3-ITD AML. Patients need more treatment options for this type of AML, which is particularly aggressive and difficult to treat. We are pleased that the FDA has filed our application for quizartinib for patients with relapsed or refractory FLT3-ITD AML, and granted priority review," said Arnaud Lesegretain, Vice President, Oncology Research and Development and Head, AML Franchise, Daiichi Sankyo. "Coupled with the recent acceptances of marketing applications for quizartinib in Japan and EU, we look forward to working with regulatory authorities in the U.S., Japan and EU to bring quizartinib to patients."

In addition to FDA priority review, quizartinib is currently under expedited regulatory review with the Japan Ministry of Health, Labour and Welfare (MHLW) and the European Medicines Agency (EMA) for the treatment of adults with relapsed or refractory AML which is FLT3-ITD positive.

About the QuANTUM-R Study
QuANTUM-R is a pivotal, global, phase 3, open-label randomized study that enrolled 367 patients with FLT3-ITD AML who were refractory to or in relapse with duration of remission of six months or less following standard first-line AML therapy with or without hematopoietic stem cell transplantation. Patients were randomized in a 2:1 ratio to receive either single agent oral quizartinib or salvage chemotherapy. The primary objective of the study was to determine whether single agent quizartinib prolonged overall survival compared to salvage chemotherapy. The study met its primary endpoint of improving overall survival.

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.

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.1 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.2 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.3 FLT3-ITD is the most common FLT3 mutation, affecting approximately one in four patients with AML.4,5,6,7 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.5,8

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.9,10

About Quizartinib
Quizartinib, the lead investigational agent in the AML Franchise of the Daiichi Sankyo Cancer Enterprise, is an oral selective FLT3 inhibitor currently in phase 3 development for adults with relapsed/refractory FLT3-ITD AML (QuANTUM-R) in the U.S. and EU; phase 3 development for newly-diagnosed FLT3-ITD AML (QuANTUM-First) in the U.S., EU and Japan; phase 2 development for relapsed/refractory FLT3-ITD AML in Japan; and, 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.

In addition to Priority Review designation, quizartinib has been granted Breakthrough Therapy designation for the treatment of adult patients with relapsed/refractory FLT3-ITD AML, and Fast Track designation for the treatment of relapsed/refractory AML by the U.S. Food and Drug Administration (FDA). Quizartinib also has been granted accelerated assessment by the European Medicines Agency (EMA) for the treatment of adults with relapsed or refractory AML which is FLT3-ITD positive, and granted Orphan Drug designation by both the FDA and the European Commission (EC) for the treatment of AML and by the Japan Ministry of Health, Labour and Welfare (MHLW) for the treatment of FLT3-mutated AML.

Quizartinib and milademetan are investigational agents that have not been approved for any indication in any country. Safety and efficacy have not been established.

On November 21, 2018 The U.S. Food and Drug Administration reported that it approved Daurismo (glasdegib) tablets to be used in combination with low-dose cytarabine (LDAC), a type of chemotherapy, for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults who are 75 years of age or older or who have other chronic health conditions or diseases (comorbidities) that may preclude the use of intensive chemotherapy (Press release, US FDA, NOV 21, 2018, View Source [SID1234531586]).

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"Intensive chemotherapy is usually used to control AML, but many adults with AML are unable to have intensive chemotherapy because of its toxicities. Today’s approval gives health care providers another tool to use in the treatment of AML patients with various, unique needs. Clinical trials showed that overall survival was improved using Daurismo in combination with LDAC compared to LDAC alone for patients who would not tolerate intensive chemotherapy," said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

AML is a rapidly progressing cancer that forms in the bone marrow and results in an increased number of abnormal white blood cells in the bloodstream and bone marrow. The National Cancer Institute at the National Institutes of Health estimates that in 2018, approximately 19,520 people will be diagnosed with AML and approximately 10,670 patients with AML will die of the disease. Almost half of the adults diagnosed with AML are not treated with intensive chemotherapy because of comorbidities and chemotherapy related toxicities.

The efficacy of Daurismo was studied in a randomized clinical trial in which 111 adult patients with newly diagnosed AML were treated with either Daurismo in combination with LDAC or LDAC alone. The trial measured overall survival (OS) from the date of randomization to death from any cause. Results demonstrated a significant improvement in OS in patients treated with Daurismo. The median OS was 8.3 months for patients treated with Daurismo plus LDAC compared with 4.3 months for patients treated with LDAC only.

Common side effects reported by patients receiving Daurismo in clinical trials include low red blood cell count (anemia), tiredness (fatigue), bleeding (hemorrhage), fever with low white blood cell count (febrile neutropenia), muscle pain, nausea, swelling of the arms or legs (edema), low platelet counts (thrombocytopenia), shortness of breath (dyspnea), decreased appetite, distorted taste (dysgeusia), pain or sores in the mouth or throat (mucositis), constipation and rash.

The prescribing information for Daurismo includes a Boxed Warning to advise health care professionals and patients about the risk of embryo-fetal death or severe birth defects. Daurismo should not be used during pregnancy or while breastfeeding. Pregnancy testing should be conducted in females of reproductive age prior to initiation of Daurismo treatment and effective contraception should be used during treatment and for at least 30 days after the last dose. The Boxed Warning also advises male patients of the potential risk of drug exposure through semen and to use condoms with a pregnant partner or a female partner that could become pregnant both during treatment and for at least 30 days after the last dose. Daurismo must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks. Patients should also be advised not to donate blood or blood products during treatment. Health care providers should also monitor patients for changes in the electrical activity of the heart, called QT prolongation.

The FDA granted this application Priority Review designation. Daurismo also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted the approval of Daurismo to Pfizer.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

On November 21, 2018 VBL Therapeutics (Nasdaq: VBLT), a clinical-stage biotechnology company focused on the discovery, development and commercialization of first-in-class treatments for cancer, reported it will provide a corporate update, in a Fireside Chat format, at the Piper Jaffray 30th Annual Healthcare Conference, to be held at the Lotte New York Palace on November 27–29, 2017, in New York City (Press release, VBL Therapeutics, NOV 21, 2018, View Source [SID1234531540]).

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Presentation Details:
Date: Wednesday, November 28
Time: 3:30-3:55 PM Eastern Time
Location: SoHo Track – Hubbard 1, 5th floor
Webcast: View Source;tp_key=0f7f922eb8

On November 21, 2018 Amneal Pharmaceuticals, Inc. (NYSE: AMRX) reported that it will present at the Piper Jaffray Healthcare Conference in New York, NY, on Tuesday, November 27, 2018 at 1:00 p.m. ET (Press release, Amneal Pharmaceuticals, NOV 21, 2018, View Source [SID1234531557]).

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To access a live webcast of the presentation, visit Amneal’s Investor Relations Web site at View Source

An archived version will be available approximately one hour after the live presentation ends and can be accessed at the same locations for 90 days.

On November 21, 2018 C4X Discovery Holdings plc (AIM: C4XD), a pioneering drug discovery company,reported its full year results for the year ended 31 July 2018 (Press release, C4X Discovery, NOV 21, 2018, View Source [SID1234533246]).

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Financial highlights
Revenue increased to £7,064,000 (2017: £143,000), driven entirely by the Indivior licensing agreement.
R&D expenses increased 15% to £6,992,000 (2017: £6,100,000), reflecting the Company’s investment in drug discovery activity and its continued development of lead drug candidates.
Total loss after tax was £1,135,000 or 2.44 pence per share (2017: £6,782,000 or 16.88 pence per share).
Post period end, C4XD completed a £10.1 million fundraise (before expenses) in October 2018 through the placing and open offer of 11,210,674 new ordinary shares in the capital of the Company (Ordinary Shares) at a price of 90 pence (GBX) per Ordinary Share.
Operational highlights
Business model validated

Licensing deal with Indivior in March 2018 for our Orexin-1 antagonist programme; $10 million upfront with up to $284 million in milestone payments.
Discovery Engine progress

C4XD’s proprietary drug asset portfolio has grown from three programmes in 2014 to nine active programmes spread across multiple therapeutic areas.
Disease areas of focus are inflammation, neurodegeneration, immune-oncology/oncology and additional opportunistic areas (e.g., addiction and diabetes).
To date, the Taxonomy3 platform has identified 285 novel, genetically-validated and disease-linked genes that will generate target insights for future discovery programmes in inflammation and neurodegeneration.
Launched Stage 1 of virtual reality-based molecular visualisation tool, 4Sight with the aim of increasing the throughput of the Company’s pre-clinical portfolio by accelerating hit generation and lead optimisation timeframes.
Partnerships

Continued to enhance core, state-of-the-art target identification and drug design capabilities through synergistic strategic partnerships:
o Joint research collaboration with e-Therapeutics plc (AIM:ETX) to identify novel mechanistic insights in Parkinson’s Disease was announced in May 2018.
Senior appointments

Eva-Lotta Allan, Non-Executive Chairman, and Natalie Walter, Non-Executive Director, were appointed to the Board of Directors in July 2018.
Dr Clive Dix, CEO of C4X Discovery, said: "C4X Discovery has had a transformational year in 2018, underlined by the successful completion of our pre-clinical licensing deal with Indivior in March. This pivotal milestone validated our business model. Our pipeline continues to progress, with NRF-2 entering a formal partnering process and excellent in vivo data on IL-17 moving this programme towards partnering. This maturing pipeline, combined with our enhanced commercial capabilities and our innovative collaborations with multiple partners, positions us well to carry out our strategy of becoming the world’s most productive drug discovery engine and delivering returns to our shareholders."

A copy of the final results presentation given by Clive Dix (Chief Executive Officer) will be released later this morning on the Group’s website at www.c4xdiscovery.com.

Analyst conference call today

Dr Clive Dix, Chief Executive Officer, will present the results at 11:30am GMT on 21 November 2018 during a live conference call. A copy of the results presentation will be released later this morning on the Company website at www.c4xdiscovery.com.