On June 18, 2019 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that the Ministry of Health, Labor and Welfare (MHLW) of Japan has approved VANFLYTA (quizartinib), an oral FLT3 inhibitor, for the treatment of adult patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML), as detected by an MHLW-approved test (Press release, Daiichi Sankyo, JUN 18, 2019, View Source [SID1234537131]).

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Approval of VANFLYTA in Japan is based on the results from the global pivotal phase 3 QuANTUM-R study and a phase 2 study of VANFLYTA in Japan in patients with relapsed/refractory FLT3-ITD AML. Results from QuANTUM-R, 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, were recently published in The Lancet Oncology.[1]

"With the approval of VANFLYTA, patients with relapsed/refractory FLT3-ITD AML in Japan will now have access to this important new treatment option that specifically targets the underlying driver of disease, and has a proven survival benefit compared to chemotherapy," said Wataru Takasaki, PhD, Corporate Officer, Head of Oncology Function and Head of R&D Division in Japan, Daiichi Sankyo. "We are proud that VANFLYTA is the first of seven new molecular entities we are committed to delivering by 2025 with the goal of transforming science into innovative treatments for patients with cancer."

Results of the global, phase 3 QuANTUM-R study demonstrated a statistically significant improvement in overall survival when comparing VANFLYTA to salvage chemotherapy. The hazard ratio for VANFLYTA was 0.76 [95% CI: 0.58, 0.98], and the median overall survival was 6.2 months [95% CI: 5.3, 7.2] in patients receiving VANFLYTA compared to 4.7 months [4.0, 5.5] salvage chemotherapy. The most common treatment-related adverse drug reactions in those receiving VANFLYTA were nausea (33.2%, 80/241 patients), electrocardiogram QT prolonged (24.9%, 60/241 patients), anemia (24.9%, 60/241 patients), and thrombocytopenia (21.2%, 51/241 patients) in the Japanese labeling. The open-label, single-arm phase 2 study evaluating VANFLYTA in Japanese patients with relapsed/ refractory FLT3-ITD AML met its primary endpoint of achieving a pre-determined composite complete remission rate at interim analysis, triggering an early stop of the study due to efficacy. The efficacy and safety profile of VANFLYTA observed in the phase 2 study in Japan appears consistent with that of QuANTUM-R.

About FLT3-ITD AML

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.[2] AML is the most common adult leukemia in Japan,[3] with approximately 5,500 new cases diagnosed each year. The five-year survival rate of AML reported from 2005 to 2011 was approximately 26 percent, which was the lowest of all leukemias.2

FLT3 gene mutations are one of the most common genetic abnormalities in AML.[4] FLT3-ITD is the most common FLT3 mutation, affecting approximately one in four patients with AML.[5] 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.[6]

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.[7], [8]

About VANFLYTA

VANFLTYA, an oral FLT3 inhibitor, is the lead product in the AML Franchise of Daiichi Sankyo. It has been granted Breakthrough Therapy designation for the treatment of adult patients with relapsed/ refractory FLT3-ITD AML by the FDA; Fast Track designation for the treatment of relapsed/refractory AML by the FDA; and, also has been granted Orphan Drug designation by both the FDA and the European Commission (EC) for the treatment of AML and by the Japan MHLW for the treatment of FLT3-mutated AML.

A broad and comprehensive development program is underway including phase 3 development in combination with standard chemotherapy in newly diagnosed FLT3-ITD AML (QuANTUM-First) in the U.S., EU and Japan; phase 1/2 development for pediatric and young adult relapsed/refractory FLT3-ITD AML in North America and the EU; 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.

Milademetan is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established. VANFLYTA currently is only approved for use in Japan.

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On June 18, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that Japan’s Ministry of Health, Labour and Welfare (MHLW) has approved Rozlytrek (entrectinib) for the treatment of adult and paediatric patients with neurotrophic tyrosine receptor kinase (NTRK) fusion-positive, advanced recurrent solid tumours (Press release, Hoffmann-La Roche, JUN 18, 2019, View Source [SID1234537129]). Rozlytrek is the first tumour-agnostic medicine to be approved in Japan that targets NTRK gene fusions, which have been identified in a range of hard-to-treat solid tumour types, including pancreatic, thyroid, salivary gland, breast, colorectal, and lung.1 It has been granted Sakigake designation and orphan drug designation by the MHLW.2

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Rozlytrek is also undergoing regulatory review in Japan for the treatment of people with ROS1 fusion-positive locally advanced or metastatic non-small cell lung cancer (NSCLC).2

"Today’s approval of Rozlytrek represents a new chapter in personalised healthcare, applying advanced diagnostics to deliver precision medicines that target cancers based on their molecular drivers instead of their location in the body," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We are proud to be at the forefront of personalised medicine with this novel treatment approach, and we look forward to working with regulatory agencies around the world to bring Rozlytrek to more patients with NTRK fusion-positive cancer, as well as to those with ROS1 fusion-positive NSCLC, as soon as possible."

The data package for this first approval of Rozlytrek includes the pivotal Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials, as well as data from the Phase I/II STARTRK-NG study in paediatric patients. Results showed:

In the pivotal Phase II STARTRK-2 study, Rozlytrek shrank tumours in more than half (objective response rate [ORR] = 56.9 percent) of people with NTRK fusion-positive solid tumours. Objective responses to Rozlytrek were seen across 10 different solid tumour types (median duration of response [DoR] = 10.4 months), including in people with and without CNS metastases at baseline.
Importantly, Rozlytrek also shrank tumours that had spread to the brain in more than half of people (intracranial response [IC] ORR = 50.0 percent).2
In the STARTRK-NG study, Rozlytrek shrank tumours also in children and adolescents who had NTRK fusion-positive solid tumours including the patients with primary CNS tumours.3
The most commonly reported adverse reactions include constipation, altered sense of taste (dysgeusia), diarrhoea, dizziness, fatigue, swelling (oedema), weight increase, anaemia, blood creatinine increase, shortness of breath (dyspnea), and nausea.2
Biomarker testing for NTRK gene fusions is the only way to identify people who may be eligible for treatment with Rozlytrek. Roche is leveraging its expertise in developing personalised medicines and advanced diagnostics, in conjunction with Foundation Medicine, to help identify people with NTRK gene fusions using a companion diagnostic that is undergoing review.

About the supporting data
The data package for this approval includes the pivotal Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials. In addition, data from the Phase I/II STARTRK-NG study in paediatric patients were also included in the submission. The studies enrolled people across 15 countries and more than 150 clinical trial sites. Tumour types evaluated in the studies included breast, cholangiocarcinoma, colorectal, gynaecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.1,2

STARTRK-2 is a Phase II, global, multicentre, open-label basket study in people with solid tumours that harbour an NTRK1/2/3, ROS1 or ALK-positive gene fusion. The primary endpoint is objective response rate (ORR), and duration of response (DoR) is a secondary endpoint. Other secondary outcome measures include time to response, clinical benefit rate, intracranial tumour response, progression-free survival (PFS), central nervous system (CNS) PFS and overall survival (OS).4
STARTRK-1 is a Phase I, multicentre, open-label dose escalation study of a daily continuous dosing schedule in people with solid tumours with NTRK1/2/3, ROS1 or ALK gene fusions in the US and South Korea. The trial assessed the safety and tolerability of Rozlytrek via a standard dose escalation scheme and determined the recommended Phase II dose.5
ALKA-372-001 is Phase I, multicentre, open-label dose escalation study of an intermittent and continuous Rozlytrek dosing schedule in people with advanced or metastatic solid tumours with TRKA/B/C, ROS1 or ALK gene fusions in Italy.2
STARTRK-NG is a Phase I/II dose-escalation and expansion study evaluating the safety and efficacy of Rozlytrek in children and adolescent patients with no curative first-line treatment option, recurrent or refractory extracranial solid tumours or primary CNS tumours, with or without TRK, ROS1 or ALK fusions.3
About NTRK fusion-positive cancer
Neurotrophic tyrosine receptor kinase (NTRK) fusion-positive cancer occurs when the NTRK1/2/3 genes fuse with other genes, resulting in altered TRK proteins (TRKA/TRKB/TRKC) that can activate signaling pathways involved in proliferation of certain types of cancer. NTRK gene fusions are tumour-agnostic, meaning they are present in tumours irrespective of site of origin. These fusions have been identified in a broad range of solid tumour types, including breast, cholangiocarcinoma, colorectal, gynaecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.1

About Rozlytrek
Rozlytrek (RXDX-101) is an oral medicine for the treatment of locally advanced or metastatic solid tumours that harbour NTRK1/2/3, as well as in development for the treatment of ROS1 gene fusions. It is a selective tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRK A/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer.6,7 Rozlytrek can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK gene fusions.6,7

Rozlytrek has been granted Priority Review by the FDA for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumours in adult and paediatric patients who have either progressed following prior therapies or as an initial therapy when there are no acceptable standard therapies, and for the treatment of people with metastatic, ROS1 fusion-positive NSCLC. It has also been granted Priority Medicines (PRIME) designation by the European Medicines Agency (EMA) and Sakigake designation and orphan drug designation by MHLW.2

On June 17, 2019 Viela Bio reported the successful completion of a $75 million private placement of its Series B preferred stock, bringing the total capital raised since the Company’s launch in February 2018 to more than $300 million (Press release, Viela Bio, JUN 17, 2019, View Source [SID1234539161]). The financing round was led by HBM Healthcare Investments, and additional new investors participating included Viking Global Investors, Cormorant Asset Management, Terra Magnum Capital Partners, Goldman Sachs, and Barer & Son Capital. Existing investors participating included Temasek.

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"We are pleased that our ongoing development of our clinical programs continues to attract capital from leading healthcare investors. This financing will support our upcoming regulatory milestone—the anticipated filing of our Biologics License Application with the U.S. FDA for our lead product candidate, inebilizumab, for the treatment of neuromyelitis optica spectrum disorder, or NMOSD," said Bing Yao, Ph.D. Executive Chairman and Chief Executive Officer. "NMOSD is a severe, debilitating, and sometimes fatal neurological disease for which there is currently no approved treatment. While our priority is to serve this patient population through the successful approval and launch of inebilizumab, we believe this financing also puts us in a strong position to pursue additional new indications with inebilizumab. Furthermore, we believe this financing will allow us to advance the entirety of our clinical pipeline, which is comprised of several additional clinical candidates for a range of rare autoimmune and inflammatory diseases."

On June 17, 2019 2019 BioNTech SE, a biotechnology company focused on the clinical development of patient-specific immunotherapy for the treatment of cancer and other serious diseases, reported the launch of DuoBody PD-L1x4-1BB product candidate clinical development (Press release, BioNTech, JUN 17, 2019, View Source [SID1234539089]). PD-L1x4-1BB is a bi-specific antibody developed in collaboration with Genmab A / S. The Phase I / IIa trial will test the bi-specific antibody in patients with metastatic or surgically non-removable solid tumors that can not be treated with standard care. The DuoBody PD-L1x4-1BB is the first co-developed product candidate to reach the clinical phase. The costs and profits of the partnership are shared 50 to 50 times.

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"The launch of the Phase I / IIa clinical trial with a product candidate that was developed in just four years confirms our highly productive partnership with Genmab," said Prof. Dr. med. Ugur Sahin, CEO of BioNTech . "The dual-immunostimulatory mechanism of action of the DuoBody PD-L1x4-1BB can address a variety of cancers, as well as providing an additional level of treatment options in our cancer therapy portfolio. We also strengthen BioNTech’s strategy of using new targets and mechanisms to unlock the full potential of the immune system for cancer immunotherapy. "

The DuoBody PD-L1x4-1BB is a novel bi-specific antibody that combines the checkpoint blockade of the inhibitory PD-1: PD-L1 signaling axis with the conditional stimulation of T cells by activating the 4-1BB receptor and thereby increase the proliferation of activated T cells for the efficient control of cancer cells. The original idea and the concept of combining the two mechanisms are based on scientific studies conducted by BioNTech. The unblinded study with the DuoBody PD-L1x4-1BB (ClinicalTrials.gov Identification Number NCT03917381) is carried out at several sites and consists of two parts: a dose-escalation study (Phase I, First-in-Human) and a dose-expansion study (Phase IIa). Primary endpoints include, above all, safety assessment, including the review of dose-limiting toxicity and adverse events.