On November 21, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the US Food and Drug Administration (FDA) has granted accelerated approval to Venclexta (venetoclax), in combination with a hypomethylating agent (azacitidine or decitabine), or low dose cytarabine (LDAC), for the treatment of people with newly-diagnosed acute myeloid leukaemia (AML), who are age 75 years or older, or for those ineligible for intensive induction chemotherapy due to coexisting medical conditions (Press release, Hoffmann-La Roche, NOV 21, 2018, View Source [SID1234531567]). AML is the most common type of aggressive leukaemia in adults and has the lowest survival rate for all types of leukaemia.

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"Today’s approval marks a significant advance for people with acute myeloid leukaemia, a highly aggressive and difficult-to-treat blood cancer," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Many people with acute myeloid leukaemia are unable to tolerate standard intensive chemotherapy, and the Venclexta combination regimens represent important new options for these patients."

This accelerated approval was based on results from the M14-358 study and the M14-387 study in people newly-diagnosed with AML including those who were ineligible for intensive induction chemotherapy. In M14-358, the rate of complete remission (CR) was 37% (n=25/67) and the rate of complete remission with partial blood count recovery (CRh) was 24% (n=16/67) for those who received Venclexta plus azacitidine. For those who received Venclexta plus decitabine, the rate of CR was 54% (n=7/13) and the rate of CRh was 8% (n=1/13). M14-387 showed a CR rate of 21% (n=13/61) and a CRh rate of 21% (n=13/61) for those who received Venclexta in combination with LDAC.

The most common serious side effects of these regimens (occurring in at least 5% of patients) were low white blood cell count with fever, pneumonia, bacteria in the blood, inflammation of tissue under the skin, device-related infection, diarrhoea, fatigue, bleeding, localized infection, multiple organ dysfunction syndrome, and respiratory failure.

The FDA’s Accelerated Approval Program allows conditional approval of a medicine that fills an unmet medical need for a serious condition. This approval of Venclexta is based on surrogate endpoints that are reasonably likely to predict clinical benefit, including CR and CRh. Continued approval for this indication may be contingent upon verification and description of clinical benefit observed in confirmatory trials.
The supplemental New Drug Application (sNDA) was granted Priority Review, a designation given to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. In addition, the FDA previously granted two Breakthrough Therapy Designations for Venclexta in people with previously untreated AML ineligible for intensive chemotherapy, either in combination with a hypomethylating agent or LDAC, based on results from these two studies. With this approval, Venclexta is available in the US for two forms of blood cancer.

Venclexta is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the US and commercialised by AbbVie outside of the US.

About the M14-358 study
The M14-358 study (NCT02203773) is an open-label, non-randomised, Phase Ib dose escalation and expansion study evaluating the safety and efficacy of Venclexta in combination with hypomethylating agents, azacitidine or decitabine, in newly-diagnosed people with AML who were 60 years or older, or ineligible to receive intensive induction chemotherapy due to coexisting medical conditions. Study endpoints included complete remission rates, overall survival and safety.

In M14-358, the rate of CR was 37% and the rate of CRh was 24% for those who received Venclexta plus azacitidine. The median follow-up for this group was 7.9 months (0.4-36 months). At the time of analysis, for patients who achieved a CR, the median observed time in remission was 5.5 months (0.4-30 months).
For those who received Venclexta plus decitabine, the rate of CR was 54% and the rate of CRh was 8%. The median follow-up for this group was 11 months (0.7-21 months). At the time of analysis, for patients who achieved a CR, the median observed time in remission was 4.7 months (1.0-18 months).
The observed time in remission for these regimens was defined as the time from the start of CR to the time of the data cut-off date or relapse from CR.
The most common adverse reactions with Venclexta plus azacitidine were nausea, diarrhoea, constipation, low white blood cell count with or without fever, low platelet count, bleeding, swelling in the arms, legs, hands and feet, vomiting, fatigue, rash and low red blood cell count.
The most common adverse reactions with Venclexta plus decitabine were low white blood cell count with or without fever, constipation, fatigue, low platelet count, stomach (abdominal) pain, dizziness, bleeding, nausea, pneumonia, infection in the blood, cough, diarrhoea, low blood pressure, pain in muscles or back, sore throat, swelling in the arms, legs hand and feet, fever and rash.
About the M14-387 study
The M14-387 study (NCT02287233) is an open-label, single-arm, Phase I/II dose escalation and expansion study evaluating the safety and efficacy of Venclexta in combination with LDAC in newly-diagnosed people with AML who were 60 years or older, or ineligible to receive intensive induction chemotherapy due to coexisting medical conditions. Study endpoints included complete remission rates, overall survival and safety.

The study showed the rate of CR and CRh was 21% for those who received Venclexta plus LDAC. The median follow-up for this group was 6.5 months (0.3-34 months). At the time of analysis, for patients who achieved a CR, the median observed time in remission was 6.05 months (0.3-25 months). The observed time in remission for this regimen was defined as the time from the start of CR to the time of the data cut-off date or relapse from CR.
The most common adverse reactions with Venclexta in combination with LDAC were nausea, low platelet count, bleeding, low white blood cell count with or without fever, diarrhoea, fatigue, constipation and difficulty breathing.
About Venclexta (venetoclax)
Venclexta is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumours, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta blocks the BCL-2 protein and works to restore the process of apoptosis.

Venclexta is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the US and by AbbVie outside of the US. Together, the companies are committed to research with Venclexta, which is currently being studied in clinical trials across several types of blood and other cancers.

In the US, Venclexta has been granted four Breakthrough Therapy Designations by the FDA: in combination with Rituxan for people with relapsed or refractory chronic lymphocytic leukaemia (CLL); as a monotherapy for people with relapsed or refractory CLL with 17p deletion; in combination with hypomethylating agents (azacitidine or decitabine) for people with untreated acute myeloid leukaemia (AML) ineligible for intensive chemotherapy; and in combination with low-dose cytarabine for people with untreated AML ineligible for intensive chemotherapy.

Venclexta is approved in more than 50 countries. Roche and AbbVie are currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.

About Acute Myeloid Leukaemia
Acute myeloid leukaemia (AML) is an aggressive form of leukaemia that starts in immature forms of blood-forming cells, known as myeloid cells, found in the bone marrow. [1] AML is the most common type of aggressive leukaemia in adults. It has the lowest survival rates of all types of leukaemia.[2] Even with the best available therapies, older patients aged 65 and over have survival rates comparable to patients with advanced lung cancer, with a five year overall survival rate of <5%.[3;4] Approximately 20,000 people in the US and 18,000 in Europe are diagnosed with AML each year. [5;6]

On November 21, 2018 OBI Pharma, Inc., a Taiwan biopharma company (TPEx: 4174), reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for OBI-888 for the treatment of Pancreatic Cancer. OBI-888 is a first in class monoclonal antibody cancer immunotherapy targeting Globo H, a glycolipid antigen (Press release, OBI Pharma, NOV 21, 2018, View Source [SID1234531559]).

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A Phase 1 study of OBI-888 has commenced enrollment at the University of Texas M.D. Anderson Cancer Center in patients with locally advanced or metastatic solid tumors, potentially including Pancreatic, Breast, Gastric, Esophageal, Colorectal and Lung Cancers.

Amy Huang, General Manager of OBI Pharma, noted, "The orphan drug designation for OBI-888 by the FDA is encouraging and is a significant step in the development of this novel monoclonal antibody drug candidate targeting Globo H. In addition to targeting other solid tumors, OBI-888 will be evaluated for the treatment of pancreatic cancer, a disease with very limited treatment options. OBI will continue our utmost efforts to develop innovative therapies for people living with cancer."

About Pancreatic Cancer

Pancreatic Cancer originates in the exocrine or endocrine pancreatic cells and is thought to be caused by poor diet, smoking, and genetic factors. Pancreatic Cancer is a deadly disease that currently affects 69,839 people in the US and has a survival rate of only 8.5% at five years. In addition, treatment options are limited to surgical resection for patients with early stages of the disease and these patients may only have a five-year survival rate of up to 34.3%. As Pancreatic Cancer is asymptomatic in early stages, a majority of patients are undiagnosed or misdiagnosed until advanced stages of the disease. Surgery is no longer effective at this stage of the disease, leaving a large population with limited treatment options.

About Orphan Drug Designation (ODD)

The orphan drug designation provides OBI Pharma with potential benefits, including market exclusivity upon regulatory approval if received, exemption of FDA application fees, and tax credits for qualified clinical trials. The FDA’s Office of Orphan Drug Products grants orphan status to support development of medicines for rare diseases or conditions that affect fewer than 200,000 people in the U.S.

About OBI-888

OBI-888 is a novel first-in-class monoclonal antibody, which selectively targets Globo H, an antigen expressed in up to 15 epithelial cancers. This Globo H targeting antibody has been shown to induce tumor-killing via antibody dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP) and complement dependent cytotoxicity (CDC).

OBI-888 is also anti-immunosuppressive and anti-angiogenic. In pre-clinical xenograft animal models in multiple tumor types (pancreatic, colon, lung, and breast), OBI-888 has demonstrated tumor shrinkage at various doses. In pre-clinical single and repeated dose toxicology studies, OBI-888 was well-tolerated, and no adverse effect was found in all the doses tested.

OBI Pharma owns global rights to OBI-888.

On November 21, 2018 Milestone Pharmaceuticals USA, Inc. reported that Joseph G. Oliveto, President and Chief Executive Officer, will present at the 30th Annual Piper Jaffray Healthcare Conference in New York on Tuesday, November 27, 2018 at 9:50 a.m. Eastern Time (Press release, Milestone Pharmaceuticals, NOV 21, 2018, View Source [SID1234531558]).

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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 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.