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FDA Approves Lenvima for Treatment of Progressive Radioiodine-refractory Differentiated Thyroid Cancer (RR-DTC)

FDA announced this February the approval of lenvima (lenvatinib), a novel investigative chemotherapy for patients with progressive radioiodine-refractory differentiated thyroid cancer (RR-DTC).  Lenvima is developed by Eisai Co., Ltd headquartered in Tokyo, Japan.  This approval is one day after the publication of Eisai’s phase III multi-nation clinical trial in the New England Journal of Medicine (NEJM), which showed significant progression-free survival (PFS) in lenvima group compared to placebo control group (median PFS 18.3 months with lenvima vs. 3.6 months with placebo). Differentiated thyroid cancer is the most common type of thyroid cancer representing about 95% of all thyroid cancers.  Some of differentiated thyroid cancers are radioiodine-refractory (RR-DTC) and treatment options for this group of patients are limited, which presents a significant unmet medical need.  Eisai’s lenvima is an oral RTK (receptor tyrosine kinase) inhibitor selectively targeting multiple different molecules including VEGFR, FGFR, RET, KIT and PDGFR, some of which are involved in tumor angiogenesis and proliferation of thyroid cancer. Lenvima was granted Orphan Drug Designation for thyroid cancer by regulatory authorities in Japan, the United States and Europe.  In addition, Lenvima was granted priority review status in the United States and accelerated assessment in Europe.  Currently Eisai is conducting several trials of lenvima attempting to treat several solid tumors, including hepatocellular carcinoma, renal cell carcinoma and non-small cell lung cancer.  Depending on the results of these trial, lenvima could become an oncology blockbuster.   Related Links:

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A New Hope for Glioblastoma

Celldex’s investigational immunotherapy rindopepimut received Breakthrough Therapy Designation from the FDA Celldex Therapeutics, headquartered in Hampton, New Jersey announced on February 23 that the US Food and Drug Administration (FDA) has granted its rindopepimut Breakthrough Therapy Designation for the treatment of adult patients with EGFRvIII-positive (epidermal growth factor receptor variant III-positive) glioblastoma (GBM).  The FDA’s decision is based largely on data from several Phase II clinical trials involving newly diagnosed or recurrent EGFRvIII-positive GBM.  Across all phase II studies, rindopepimut prolonged overall survival well beyond what has been observed in the corresponding patient populations historically, marking an important milestone for this difficult to treat disease.  And importantly, these studies also demonstrate that rendopepimut is well tolerated in patients. Rindopepimut is an investigational immunotherapeutic vaccine that targets EGFRvIII.  EGFRvIII is a mutated form of the epidermal growth factor receptor (EGFR) that is only expressed in cancer cells and the expression of this form of EGFR promotes cancer growth.  EGFRvIII is present in about 25-40% of GBM tumors and EGFRvIII-positive GBM is typically associated with poor prognosis than the overall GBM population. According to Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics, Glioblastoma patients have extremely limited treatment options, with only three new drugs approved in more than twenty years. The FDA’s decision to grant Breakthrough Designation underscores rindopepimut’s therapeutic potential, and brings new hope to patients with glioblastoma.   Related Links:

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Improving Gene Editing with Drugs: An Interview with Dr. Sheng Ding

CRISPR/Cas technology adapted from the bacterial immune system has received tremendous attention from medical research and technology community.  With the advent of genomic sequencing and subsequent disease predisposition gene discovery, this technology offers enormous opportunities to correct genetic defects for patients suffering from rare hereditary diseases currently with no effective therapy.  Although CRISPR/Cas technology is capable of precise genome editing, it is also well known for its low efficiency.  Recently, a report published in the latest issue of Cell Stem Cell from the laboratories of Dr. Ding Sheng, and his collaborator Dr. Lei Qi, co-senior author from the Stanford University,  have discovered a way to enhance the efficiency of CRISPR with the introduction of a few key chemical compounds. Dr. Sheng Ding is current the William K. Bowes, Jr. Distinguished Investigator and Professor at Gladstone Institute of Cardiovascular Disease, and Department of Pharmaceutical Chemistry, University of California San Francisco. Today, we sat down with Dr. Ding to hear his thoughts on CRISPR and the research findings. Your original interest is in stem cell research, what attracted you to CRISPR technology? Ding: Genome editing is an essential tool for conducting stem cell research, such as generating reporter cell lines, making isogenic iPSC lines for disease modeling, and performing genetic manipulation in stem cells to understand basic biology. In addition, stem cell is a great vehicle for many gene therapy approaches. It is quite natural to get into using CRISPR, which is much more convenient and powerful than previous genome editing techniques. Lastly, we are simply curious whether CRISPR mediated process could be modulated by small molecules, which is a central theme of what we do in research. Can you elaborate a bit more on your recent findings in the context of the power of CRISPR? Ding: Despite CRISPR technology is convenient and powerful, it is still at its infancy. Uncovering new ways to modulate its efficiency and precision, and better understanding its underlying mechanisms would be highly useful. Our recent work only scratched surface of it, and focused mostly on the precise editing of genome sequences through homology-directed repair (HDR), which is very inefficient. Through high throughput phenotypic screening of small molecules, we identified a couple of molecules that can significantly enhance the HDR-based high fidelity genome editing. Interestingly, we also identified inhibitors of HDR, which can enhance frame shift insertion and deletion mutations (for making sequence-specific gene knockout) mediated by non-homologous end joining (NHEJ). How do you see these new insight may be translated to drug discovery and clinic? Ding: Having more efficient CRISPR editing capability will certainly make it more useful for in vitro applications (such as making disease-specific cell lines for drug discovery). In addition, more precise control over CRISPR editing activity (e.g., turning it on and off) would potentially allow more safely deployment of CRISPR for therapeutic applications. Any insight regarding the opportunities to combine CRISPR and stem cell technologies to tackle major diseases? Ding: You are right that it is currently pursued by many researchers to combine CRISPR and stem cell technologies to tackle many untractable diseases. We are quite fortunate to be in the field and contribute our expertise.

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An Interview with Dr. Rick Panicucci, Vice President of Pharmaceutical Development Services

We are delighted to announce that Dr. Rick Panicucci has joined WuXi as Vice President of Pharmaceutical Development Services. Prior to WuXi, Rick was Global Head of Chemical and Pharmaceutical Profiling (CPP) at Novartis from 2004.  His responsibilities include analytics, solid state chemistry and formulation development of all small molecule therapeutics in early development. Additional responsibilities include developing novel drug delivery technologies for small molecules and large molecules including siRNA.  Rick currently also holds the position of Adjunct Professor at Massachusetts College of Pharmacy.  This week we sat down with Rick to discuss his career and thoughts on the industry. What inspired you to join WuXi after over 20 successful years at both biotech and pharma including most recently as Global Head of Chemical and Pharmaceutical Profiling at Novartis? Panicucci: I am really excited about joining WuXi.  WuXi is a well recognized leader with a best-in-class capability and technology platform, a proven track record, and deep commitment to partners and patients.  With my experience in Biotech and Big Pharma I will be able to use all my learning to support our customers and partners achieve success. What can you tell us about the PDS business unit at WuXi that you will be deeply involved as the scientific leader, and what goals you aspire to achieve? Panicucci: We aspire to make the WuXi Pharmaceutical Development Service (PDS) platform the best-in-class in the world. WuXi has built an impressive open-access and integrated platform for discovery and development to serve our partner’s need.  For the past six years, PDS has served over 300 partners and delivered over 750 clinical batches to support our partner’s clinical studies all over the world.  Our quality system has been inspected and approved by US FDA, MPA and China cFDA.   We will continue to build capability and capacity, and integrate with our API business to provide integrated CMC services to serve our partner’s needs. Having been in major pharma working with external collaborators and now you are on the service platform side,  what do you see are secrets to successful collaborations? Panicucci: I would say that communication is most important.  It is important to listen to our customers and really try to understand what their needs are and then map out and communicate a strategy to them that allows them to be successful in their projects.  In this scenario everyone “wins” including patients that will benefit from new therapies. As an internationally recognized formulation expert,  what do you predict will be some of the most significant developments in your field upcoming, and how they may impact better solution for patients? Panicucci: The biggest challenge will be the drug device combinations.  Patients of the future will expect integrated technologies (electronic and special formulations) to be part of the therapeutic solutions.  I have studied this area for years and am really looking forward to exploring the possibilities at WuXi.

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Gene Therapy Offers Potentially New Treatment for beta-Thalassemia Patients

Bluebird Bio Inc., a leading gene therapy biotech company based in Cambridge, Massachusetts, announced on February 2 that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to one of its investigational drugs, LentiGlobin® BB305 for the treatment of transfusion-dependent patients with beta-thalassemia major. Beta-thalassemia is a rare genetic disease affecting 40,000 newborn children annually worldwide.  It is caused by mutations in the beta-globin gene (HBB).  HBB encodes beta chains of hemoglobin and mutation of this gene causes different types of rare blood genetic diseases (Sickle Cell disease or beta thalassemia).  Depending on the severity of symptoms, beta-thalassemia is clinically divided into two types: thalassemia major and thalassemia intermedia with thalassemia major being more severe. Presently, the existing treatment options for these patients have significant side effects and limitations. LentiGlobin BB305 developed by Bluebird Bio utilizes an improved lentiviral vector to insert a correct copy of human beta-globin gene into the patient’s own hematopoietic stem cells ex vivo and then transplanting those modified cells into the patient through infusion into the bloodstream.  LentiGlobin BB305 is currently undergoing three clinical trials globally aimed at treating both beta-thalassemia and sickle cell disease.   Related links:

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