On April 23, 2018 Eli Lilly and Company (LLY) and Incyte Corporation (INCY) reported that the U.S. Food and Drug Administration’s (FDA) Arthritis Advisory Committee recommended approval of the 2-mg dose of baricitinib, a once-daily oral medication for the treatment of moderately-to-severely active rheumatoid arthritis (RA) for adult patients who have had an inadequate response or intolerance to methotrexate (Press release, Incyte, APR 23, 2018, View Source [SID1234525686]). While the Advisory Committee unanimously supported the efficacy of the 4-mg dose of baricitinib, it did not recommend approval of the 4-mg dose of baricitinib for the proposed indication based on the adequacy of the safety and benefit-risk profiles.

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"We are confident that baricitinib, if approved, can help people in the U.S. manage the challenges of living with RA," said Christi Shaw, president of Lilly Bio-Medicines. "While we are disappointed with the Advisory Committee’s assessment of the data for the 4-mg dose, we are confident in the positive benefit-risk profile of both the 2-mg and the 4-mg doses. We look forward to continuing our work with the FDA on our New Drug Application (NDA) and are hopeful that baricitinib will receive approval in the coming months."

Baricitinib 2-mg and 4-mg doses are approved in more than 40 countries, including the member states of the European Union and Japan.

For both doses, the Advisory Committee voted to support the assessment that baricitinib’s data provide substantial evidence of efficacy. For the 2-mg dose, the Advisory Committee voted in favor of the assessment that baricitinib’s safety data adequately support its approval. For the 4-mg dose, the Advisory Committee voted against the assessment that baricitinib’s safety data was adequate to support its approval based on the proposed indication.

The Advisory Committee’s recommendation was based on baricitinib’s global development program, which included four completed Phase 3 studies. In total, 3,492 patients, who represented a range of treatment experiences, received baricitinib in the global RA development program. The Phase 3 studies evaluated baricitinib’s treatment impact related to RA signs and symptoms, physical function, joint damage progression and other patient-reported outcomes. The Phase 3 program also evaluated recognized risks for RA patients, including serious infection, malignancy, major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and gastrointestinal perforations, along with key laboratory changes. The safety profile of baricitinib is based on 7,860 patient-years of exposure.

"Despite advances in the management of RA over the last 20 years, which include early treatment, optimized use of traditional therapies for rheumatic disease and the advent of newer medications such as biologics, many patients are still struggling to meet treatment targets, and live with debilitating pain, fatigue and other symptoms of RA," said Peter Taylor, MA, PhD, professor, University of Oxford, an expert who attended the Advisory Committee Meeting. "Baricitinib could be a promising option for RA patients in the U.S. who are not achieving adequate disease control with currently available treatments."

The FDA is not required to follow the Advisory Committee’s recommendation, but will consider it during its review of the NDA for baricitinib.

About Baricitinib
Baricitinib is a once-daily oral JAK inhibitor currently in clinical studies for inflammatory and autoimmune diseases. There are four known JAK enzymes: JAK1, JAK2, JAK3 and TYK2. JAK-dependent cytokines have been implicated in the pathogenesis of a number of inflammatory and autoimmune diseases, suggesting that JAK inhibitors may be useful for the treatment of a broad range of inflammatory conditions, including rheumatoid arthritis.

In December 2009, Lilly and Incyte announced an exclusive worldwide license and collaboration agreement for the development and commercialization of baricitinib and certain follow-on compounds for patients with inflammatory and autoimmune diseases. Baricitinib was submitted for regulatory review seeking marketing approval for the treatment of rheumatoid arthritis in the U.S., the European Union and Japan in 2016. Baricitinib was approved in the EU in February 2017 and in Japan in July 2017. In April 2017, the U.S. Food and Drug Administration issued a Complete Response Letter on the New Drug Application for baricitinib. To date, baricitinib has been approved in more than 40 countries and remains under review in several other markets.

On April 23, 2018 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas" ) reported that it submitted on March 23, 2018, a new drug application (NDA) for marketing approval of gilteritinib (generic name) in Japan for the treatment of adult patients with FLT3 mutation-positive (FLT3mut+) relapsed or refractory acute myeloid leukemia (AML) (Press release, Astellas Pharma US, APR 23, 2018, View Source [SID1234525608]). Astellas also submitted a NDA for approval of gilteritinib in the same patient population to the U.S. Food and Drug Administration (FDA) on March 29, 2018 (U.S. time) following the submission in Japan. The applications for marketing approval for gilteritinib are based on data from the ongoing pivotal Phase 3 ADMIRAL study investigating gilteritinib in adult patients with FLT3mut+ relapsed or refractory AML.

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Astellas is a pharmaceutical company dedicated to improving the health of people around the world. (PRNewsFoto/Astellas Pharma Inc.)

AML is a cancer that impacts the blood and bone marrow, and its incidence increases with age. In Japan, approximately 5,500 patients are diagnosed with AML each year1. Gilteritinib is an investigational compound that has demonstrated inhibitory activity against both internal tandem duplication (ITD) and tyrosine kinase domain (TKD), FLT3 mutations that are seen in approximately one-third of patients with AML.

In October 2015, the Japanese Ministry of Health, Labor and Welfare (MHLW) announced the selection of gilteritinib as one of the first products designated for SAKIGAKE2.

(1)

KantarHealth. TREATMENT ARCHITECTURE: JAPAN LEUKEMIA, ACUTE MYELOID. CancerMPact Japan, February 2017.

(2)

SAKIGAKE: SAKIGAKE designation system can shorten the review period with the following 3 approaches: 1) Prioritized Consultation, 2) Substantial Pre-application Consultation and 3) Prioritized Review.

And also, the system will help promote the development with the following 2 approaches: 4) Review Partner System (to be conducted by the Pharmaceuticals and Medical Devices Agency) and 5) Substantial Post-Marketing Safety Measures.

About Gilteritinib
Astellas is currently investigating gilteritinib in various FLT3 mutation-positive AML patient populations through several Phase 3 trials. Visit View Source to learn more about ongoing gilteritinib clinical trials.

Gilteritinib was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global rights to develop, manufacture and potentially commercialize gilteritinib. Gilteritinib has been granted Orphan Drug and Fast Track designation by the U.S. FDA, Orphan Drug Designation by the European Commission, and SAKIGAKE Designation and Orphan Drug Designation by the Japan Ministry of Health, Labor and Welfare.

About the ADMIRAL Study
The Phase 3 ADMIRAL trial is an open-label, multicenter, randomized study of gilteritinib versus salvage chemotherapy in adult patients with FLT3 mutations who are refractory to or have relapsed after first-line AML therapy. The co-primary endpoints of the trial are OS (Overall Survival) and CR (complete remission) / CRh (CR with partial hematological recovery) rate and the study is still ongoing. The study enrolled 371 patients with FLT3 mutations present in bone marrow or whole blood, as determined by central lab. Subjects have been randomized in a 2:1 ratio to receive gilteritinib (120 mg) or salvage chemotherapy.

On April 23, 2018 Advaxis, Inc. (NASDAQ:ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported that Kenneth A. Berlin has been appointed as President and Chief Executive Officer, effective April 23, 2018, and will also serve as a Director of the company (Press release, Advaxis, APR 23, 2018, View Source [SID1234525582]). Interim CEO Anthony Lombardo will remain with Advaxis for a period of time to ensure a smooth transition to Mr. Berlin.

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In addition, Andres A. Gutierrez, M.D., Ph.D. has been named Executive Vice President, Chief Medical Officer, effective April 23, 2018. Advaxis also announced that CFO Sara Bonstein will be leaving the company as of April 30, 2018 to pursue a new professional opportunity. The Company is actively engaged in the search for a new CFO, and will announce an interim appointment shortly.

"After a comprehensive and methodical search, we are very pleased to announce that Ken Berlin has agreed to join Advaxis as President and CEO, and that Dr. Andres Gutierrez is joining our team as CMO. Both of these executives are eminently qualified for their new positions, and we expect to benefit greatly from their expertise. Under their leadership, we look to the future of the company with excitement and confidence," stated David Sidransky, M.D., Chairman of the Board. "On behalf of the Board, I would like to take this opportunity to sincerely thank Sara Bonstein and Anthony Lombardo for their valued service to the company as CFO and interim CEO, respectively, and extend best wishes to both of them."

Mr. Berlin joins Advaxis from Rosetta Genomics, where since 2009 he was President and Chief Executive Officer. During his tenure at Rosetta, Mr. Berlin spearheaded the effort of repositioning the company for commercial success with various microRNA-based oncology diagnostic products and raised nearly $100 million in capital to fund these efforts. Prior to Rosetta Genomics, Mr. Berlin was Worldwide General Manager at cellular and molecular cancer diagnostics developer Veridex, LLC, a Johnson & Johnson company. At Veridex he grew the organization to over 100 employees, launched three cancer diagnostic products, led the acquisition of its cellular diagnostics partner, and delivered significant growth in sales as Veridex transitioned from an R&D entity to a commercial provider of oncology diagnostic products and services. During Mr. Berlin’s tenure, Veridex received numerous awards including recognition from the Cleveland Clinic and Prix Galien for the use of its innovative CellSearch technology in the fight against cancer.

Mr. Berlin joined Johnson & Johnson in 1994 and served as corporate counsel for six years. He led and participated on the legal team that oversaw several mergers, acquisitions, divestitures and commercial transactions. He then held positions of increasing responsibility within Johnson & Johnson and a number of its subsidiary companies. From 2001 until 2004 he served as Vice President, Licensing and New Business Development in the pharmaceuticals group, and from 2004 until 2007 served as Worldwide Vice President, Franchise Development, Ortho-Clinical Diagnostics. He has been responsible for numerous licensing and/or research collaboration deals in oncology, metabolic disease, cardiovascular disease, CNS and women’s health, including the ex-U.S. license to Millennium Pharmaceutical’s VELCADE, a first-in-class, oncology therapeutic with peak reported sales outside the U.S. of approximately $1.8 billion.

"Ken brings to Advaxis a truly valuable combination of executive leadership experience with large and small, development-stage and commercial companies with a particular expertise in oncology. He has a proven ability to raise capital, launch products, achieve rapid sales growth, build businesses and complete strategic M&A and licensing transactions. We are fortunate to have Ken as our new chief executive," commented Dr. Sidransky.

"The opportunity to join Advaxis at such a pivotal and active time is very exciting," stated Mr. Berlin. "I look forward to building on the company’s strong foundations and to maximize the value of our Lm-based platform technology worldwide and in multiple indications."

Mr. Berlin holds an A.B. degree from Princeton University and a J.D. from the University of California Los Angeles School of Law.

Dr. Gutierrez will be responsible for all global clinical development and regulatory initiatives for Advaxis’ novel Lm-based antigen delivery platform. He has more than 25 years of experience in clinical oncology and drug development and joins Advaxis from Oncolytics Biotech, Inc., where he served as Chief Medical Officer. Prior to Oncolytics, Dr. Gutierrez was Chief Medical Officer at SELLAS Life Sciences Group and was Medical Director, Early Development Immuno-Oncology at Bristol-Myers Squibb, where he oversaw the development of translational and clinical development of immuno-oncology programs in solid tumors and hematological malignancies. Earlier, Dr. Gutierrez was Medical Director for several biotechnology companies including Sunesis Pharmaceuticals, BioMarin Pharmaceutical, Proteolix and Oculus Innovative Sciences, leading key programs with talazoparib and carfilzomib, among others . Prior to Oculus, he served as Director of the Gene & Cell Therapy Unit at the National Institutes of Health in Mexico City and as a consultant physician at the Hospital Angeles del Pedregal.

"We are delighted to welcome Dr. Gutierrez to Advaxis and are confident he will be a valuable addition to our executive team. He is an accomplished leader and physician with a track record of success in developing novel oncology drugs, putting patients first and delivering results," said Dr. Sidransky. "Dr. Gutierrez has played a key role in the advancement of clinical trials in all stages of development, through to drug approvals. We look forward to benefitting from his expertise in oncology drug development as he leads the clinical development of our immune-oncology platform."

"I am excited to be joining Advaxis at this important time in the company’s evolution with multiple clinical programs planned and underway, and look forward to contributing to the impressive progress made to date by the Advaxis team in advancing its innovative Lm-based antigen delivery technology across a number of important cancer indications," said Dr. Gutierrez. "Advaxis has a promising future as we continue to accelerate the development of our pipeline and bring innovative new medicines to patients."

Dr. Gutierrez received his M.D. and a Ph.D. in biomedical science from the National University of Mexico, with board certification in internal medicine and a fellowship in clinical oncology at the Hammersmith Hospital in London. He has presented clinical data at more than 85 scientific and medical meetings, has written numerous peer-reviewed articles, is a contributing author on nine medical textbooks and is named on 20 patents relating to drug development.

On April 23, 2018 ArQule, Inc. (Nasdaq: ARQL) reported it will report financial results for the first quarter of 2018 before the market opens on Monday, May 7, 2018 (Press release, ArQule, APR 23, 2018, View Source [SID1234525583]).The Company will hold a conference call and webcast on the same day at 9:00 a.m. ET to discuss these results and provide a general business update.

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The live webcast can be accessed in the "Investors and Media" section of our website, www.arqule.com, under "Events & Presentations." You may also listen to the call by dialing (877) 868-1831 within the U.S. or (914) 495-8595 outside the U.S. A replay will be available two hours after the completion of the call and can be accessed in the "Investors & Media" section of our website, www.arqule.com, under "Events and Presentations."

On April 23, 2018 Castle Biosciences, Inc., a provider of molecular diagnostics to improve cancer treatment decisions, reported presentation of results demonstrating that the use of the DecisionDx-Melanoma gene expression profile (GEP) test with American Joint Committee on Cancer (AJCC) staging can improve accuracy of recurrence and metastasis risk for patients with localized cutaneous melanoma (Press release, Castle Biosciences, APR 23, 2018, View Source [SID1234525585]).

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The study titled, "Improved identification of high-risk, Stage I-II cutaneous melanomas with the combination of American Joint Committee on Cancer staging and a 31-gene expression profile test result," was presented as a poster at the 3rd Annual Real World Dermatology for Physician Assistants and Nurse Practitioners conference, held April 20-22, 2018 in Orlando, Florida.

"In this large Stage I-II melanoma study population, the DecisionDx-Melanoma test improved risk prediction when used in combination with AJCC risk assessment and showed independent prognostic value," commented study co-author Robert W. Cook, PhD, Vice President, Medical Affairs and R&D at Castle Biosciences. "Providing this information for risk assessment is important to help guide patient management decisions for improved patient outcomes."

Study Background

For patients with cutaneous melanoma, accurate assessment of recurrence risk is important to guide management plans including imaging based surveillance, follow-up frequency and sentinel lymph node biopsy recommendations that can lead to early detection of metastatic disease. National guidelines suggest surveillance plans based on AJCC stage, with Stage I-IIA considered low risk and Stage IIB-IV considered high risk. The DecisionDx-Melanoma GEP test accurately and independently predicts risk of recurrence and metastasis, classifying patients as Class 1A (lowest risk) Class 1B/2A (lower or intermediate risk) or Class 2B (highest risk).

This study of 485 Stage I and II patients from a multicenter cohort with long-term outcomes assessed the use of AJCC staging combined with results from the DecisionDx-Melanoma GEP test to improve recurrence risk prediction.

Key Study Findings:

Patients who were classified as high risk by both AJCC staging (Stage IIB-C) and the GEP test (Class 2B) had significantly lower 5-year recurrence-free survival (RFS 33.4%), distant metastasis-free survival (DMFS 49.5%) and melanoma specific survival (MSS 86.7%) compared to those identified as low risk by both methods (RFS 96.1%, DMFS 97.3%, MSS 99.6%, p<0.0001 for all comparisons).
Importantly, patients who were assessed as low risk using AJCC staging (Stage I-IIA) but high risk using the GEP test also demonstrated significantly worse outcomes (RFS 60.9%, DMFS 75.8%, MSS 85.9%) compared to patients who were assessed as low risk using both methods (p<0.0001 for all comparisons).
Multivariate Cox regression analysis indicated that both GEP high risk and AJCC high risk were significant and independent predictors of RFS (GEP HR 6.8; AJCC HR 2.98, p<0.0001, both groups) and DMFS (GEP HR 8.5; AJCC HR 2.5, p<0.001, both groups). For MSS, GEP Class 2B was the only significant predictor (GEP HR 43.8, p<0.001; AJCC HR 1.04, p<0.94).
Clinical Impact of DecisionDx-Melanoma Test

A second poster titled, "Clinical impact of a 31-gene expression profile test for cutaneous melanoma patients: a review of clinical utility studies," was also presented at the conference.

The poster highlights key findings across 5 published clinical utility studies, including:

In prospective and retrospective multicenter clinical utility studies, the inclusion of the DecisionDx-Melanoma test in risk assessment resulted in significant differences in follow-up and surveillance when comparing low- and high-risk patients.
Findings across multiple clinical impact studies show that incorporation of the GEP test consistently impacts clinical management decisions for approximately 1 in 2 patients tested.
Use of the DecisionDx-Melanoma GEP test in combination with conventional staging methods can help develop a more efficient and individualized follow-up plan based on clinical factors and tumor biology.
About DecisionDx-Melanoma
The DecisionDx-Melanoma test uses tumor biology to predict individual risk of melanoma recurrence and sentinel lymph node positivity independent of traditional factors. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in three multicenter studies that have included 690 patients and have demonstrated consistent results. Performance has also been confirmed in four prospective studies including 702 patients. The consistent high performance and accuracy demonstrated in these studies, which combined have included over 1,300 patients, provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter studies which included over 1,400 patients. Clinical impact has been demonstrated in multicenter and single-center studies showing that test results impact clinical management decisions for one of every two patients tested. More information about the test and disease can be found at www.SkinMelanoma.com.