DOCSLIB.ORG

Pipeline Report May 2020

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Pipeline Report May 2020 Pipeline Report May 2020 Pipeline Report May 2020 © 2020 Envolve. All rights reserved. Page 1 This quarterly at-a-glance publication is developed by our Clinical Pharmacy Drug Information team to Table of Contents increase your understanding of the drug pipeline, ensuring you’re equipped with insights to prepare Recent Specialty Drug Approvals 1 for shifts in pharmacy benefit management. In this issue, you’ll learn more about these key themes and notable drugs: Recent Non-Specialty Drug Approvals 2 > Despite the FDA’s recent intense focus on COVID- 19-related activities, oncology drug pipeline is one Upcoming Specialty Products 3 therapeutic area which remains vibrant in the immediate term. This is evidenced by the consistent rate of FDA approvals, as well as acceptance of New Drug and Biologic License Applications for review. In fact, multiple oncology agents were Upcoming Non-Specialty Products 7 FDA-approved several months ahead of schedule, underscoring the urgency with which the FDA continues to act on oncologic agents. Biosimilars 9 > Several pipeline agents on this quarterly report are worth highlighting as possible new alternatives in high-cost disease states with few therapeutic options. These Generic Specialty Agents 10 agents include viltolarsen in the treatment of Duchenne muscular dystrophy (DMD), fostemsavir in the treatment of heavily treatment-experienced adult patients with HIV, and roxadustat which offers the first oral alternative to Generic Non-Specialty Agents 11 injectable agents such as Aranesp, Epogen and Procrit, for the treatment of anemia associated with chronic kidney disease. To prepare this report, our team accesses a wide range of clinical resources. This information is then analyzed, resulting in updates across multiple disease states including recent and anticipated drug approvals, key changes in the biosimilar agent landscape, and notes on recent and anticipated generic product launches. Our pipeline report is just one of many ways we’re committed to providing helpful tools and resources to our clients and partners. We look forward to sharing more updates with you in the months ahead. Ross Hoffman, MD To provide comments, feedback or requests for report enhancements, please email us at [email protected]. Pipeline Report Recent Specialty Drug Approvals May 2020 FDA Approval AcariaHealth (AH) Cost (AWP Drug Name Manufacturer Indication(s) Comments Date Access Status Package Price) ENDOCRINOLOGY Isturisa • For the treatment of adults who either cannot undergo pituitary osilodrostat • Novartis • Cushing’s disease 3/6/2020 Pending launch gland surgery or have undergone the surgery but still have the $410,400/ year oral tablets disease. NEUROLOGY Vyepti • Alder • Efficacy demonstrated for both episodic and chronic migraines. eptinezumab-jjmr • Migraine headaches 2/21/2020 Limited access $7,176/ year BioPharmaceuticals • 30-minute infusion once every 12 weeks. intravenous infusion Zeposia • Relapsing forms of multiple • Same mechanism of action as Gilenya, but potentially less cardiac ozanimod • Celgene 3/25/2020 Pending launch Pending launch sclerosis (MS) adverse effects. oral capsules ONCOLOGY Sarclisa • Proposed for use in combination with pomalidomide and isatuximab-irfc • Sanofi • Muliple myeloma 3/2/2020 Limited access dexamethasone for third-line treatment. $141,960/ year intravenous infusion • Same mechanism of action and indication as Darzalex. Koselugo • Neurofibromatosis type 1 (NF1) • AstraZeneca • Approved for the treatment of pediatric patients aged two years and selumetinib with plexiform neurofibromas 4/10/2020 Limited access $156,960/ year • Merck older with symptomatic, inoperable PNs. oral capsules (PN) Jelmyto • Is the only FDA-approved non-surgical treatment for this indication, mitomycin • UroGen for the treatment of low-grade upper tract disease that is $363,392/ 14-month • Urothelial carcinoma 4/15/2020 Pending launch pyelocalyceal instillation Pharmaceuticals unamenable to endoscopic resection or with contraindication to course of therapy gel nephroureterectomy. Pemazyre • For the treatment of locally advanced/metastatic or surgically pemigatinib • Incyte • Cholangiocarcinoma 4/17/2020 Limited access unresectable disease with FGFR-2 translocation in patients who $285,600/ year oral tablets failed previous therapy. • Approved for use in combination with trastuzumab and capecitabine Tukysa • Cascadian for patients who have received one or more prior anti-HER2-based tucatinib • Breast cancer 4/17/2020 AH has access $266,400/ year Therapeutics regimens in the metastatic setting. oral tablets • Showed efficacy in patients both with or without brain metastases. Trodelvy • Antibody-drug conjugate (ADC). sacituzumab govitecan- • Triple negative breast cancer • Impressive clinical activity seen in a refractory setting. • Immunomedics 4/22/2020 Limited access $251,160/ year hziy (TNBC) • Is the first and only ADC approved for the treatment of metastatic intravenous infusion TNBC. • Approved for both first-line and previously treated patients with Tabrecta • Non-small cell lung cancer metastatic MET exon 14 skipping (METex14) mutated disease. capmatinib • Novartis 5/6/2020 Pending launch Pending launch (NSCLC) • The MET mutation is seen in an estimated 3% - 4% of all patients oral tablets with NSCLC. © 2020 Envolve. All rights reserved. Page 1 Pipeline Report Recent Non-Specialty Drug Approvals May 2020 FDA Approval Cost (AWP Package Drug Name Manufacturer Indication(s) Comments Date Price) CARDIOVASCULAR Nexletol • For use in combination with maximally tolerated statin therapy. • Esperion bempedoic acid • Hypercholesterolemia 2/21/2020 • Not as potent as Praluent and Repatha, but considerably less $4,818/ year Therapeutics, Inc. oral tablets expensive. Nexlizet • For use in combination with maximally tolerated statin therapy. • Esperion bempedoic acid /ezetimibe • Hypercholesterolemia 2/26/2020 • Not as potent as Praluent and Repatha, but considerably less Pending launch Therapeutics, Inc. oral tablets expensive. GASTROINTESTINAL Pizensy • Chronic idiopathic • Once daily dosing. lactitol • Braintree labs 2/12/2020 Pending launch constipation • Mixed with 4-8 oz of fluid (water, juice, coffee, etc.). oral solution Barhemsys • Post-operative nausea and amisulpride • Acacia 2/26/2020 • Approved for use as both treatment and prophylaxis. Pending launch vomiting intravenous infusion NEUROLOGY Nurtec ODT • Will compete with generically available oral triptans for the same rimegepant • Biohaven • Migraine headaches 2/27/2020 $12,240/ year indication. oral tablets Ongentys • Once daily dosing. • Neurocrine opicapone • Parkinson’s disease (PD) 4/24/2020 • Intended as adjunct to levodopa therapy in patients experiencing “off” Pending launch Biosciences oral capsules episodes. © 2020 Envolve. All rights reserved. Page 2 Pipeline Report Upcoming Specialty Products May 2020 Anticipated Approval Drug Name Manufacturer Indication(s) Mechanism of Action Comments Date CARDIOVASCULAR • Potentially large impacted population. Revascor • Proposed for use in left ventricular systolic dysfunction. rexlemestrocel-L • Mesoblast • Chronic heart failure • Stem cell therapy 2020 • Would be reserved for use in patients who had failed multiple other intramyocardial injection therapies. • Administered in the doctor’s office as twice yearly dosing. • Proprotein convertase subtilisin/ inclisiran • Would compete with the PCSK9 binding inhibitors for high • Novartis • Hypercholesterolemia kexin type 9 (PCSK9) synthesis 12/1/2020 subcutaneous injection cardiovascular risk patients who are already on maximized statin inhibitor therapy. COAGULATION DISORDERS Roctavian • Proposed for the treatment of adults with severe disease (~60% of the valoctocogene • BioMarin • Hemophilia A • Gene therapy total hemophilia A population). 8/21/2020 roxaparvovec • Current standard of care is factor VIII replacement therapy. intravenous infusion AMT-061 • For the treatment of adults with severe disease (~40% of the total etranacogene • Uniqure • Hemophilia B • Gene therapy hemophilia B population). 2020-2021 dezaparvovec • Current standard of care is factor IX replacement therapy. intravenous infusion • For the treatment of adults with severe disease (~60% of the total SPK-8011 • Spark • Hemophilia A • Gene therapy hemophilia A population). 2021 intravenous infusion • Roche • Current standard of care is factor VIII replacement therapy or Hemlibra. ENDOCRINOLOGY UX 007 • Currently available therapies include avoidance of fasting, low-fat/high • Long-chain fatty acid triheptanoin • Ultragenyx • Fatty acid replacement therapy carbohydrate diets, carnitine and medium-chain triglyceride (MCT) oil, 7/31/2020 oxidative disorder oral liquid a medical food product. • Once daily oral therapy. BCX7353 • Hereditary angioedema • Selective inhibitor of plasma • All other HAE therapies are IV or SC injections. berotralstat • BioCryst 12/3/2020 (HAE) kallikrein • High demand for this more convenient, less invasive dosage form is oral capsules anticipated. HEPATOLOGY OCA • Non-alcoholic • Farnesoid X-activated receptor • New indication for Ocaliva. obeticholic acid • Intercept 6/26/2020 hepatosteatosis (NASH) agonist • Would be the first FDA-approved pharmacologic therapy for NASH. oral tablets © 2020 Envolve. All rights reserved. Continued Page 3 Pipeline Report Upcoming Specialty Products May 2020 Anticipated Approval Drug Name Manufacturer Indication(s) Mechanism of Action Comments Date IMMUOLOGY • IV infusion twice weekly for
Load more

Recommended publications
  • Print PDF Opens in a New Window
    CADTH ISSUES IN EMERGING HEALTH TECHNOLOGIES Informing Decisions About New Health Technologies Issue July 173 2018 Monoclonal Antibodies for Osteoarthritis of the Hip or Knee Image courtesy of iStock CADTH ISSUES IN EMERGING HEALTH TECHNOLOGIES 1 Authors: Sirjana Pant, Ke Xin Li, Melissa Severn Cite As: Monoclonal Antibodies for Osteoarthritis of the Hip or Knee. Ottawa: CADTH; 2018. (CADTH issues in emerging health technologies; issue 173). Acknowledgments: CADTH would like to acknowledge the contribution of Dr. Tom Appleton, MD, PhD, FRCPC, Assistant Professor, Rheumatologist; Department of Medicine, Department of Physiology and Pharmacology, The University of Western Ontario; Clinician Scientist, Lawson Health Research Institute; The Rheumatology Centre, St. Joseph’s Health Care London; for his review of the draft version of this bulletin. ISSN: 1488-6324 (online) Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy- makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services.
    [Show full text]
  • Pharmacologic Considerations in the Disposition of Antibodies and Antibody-Drug Conjugates in Preclinical Models and in Patients
    antibodies Review Pharmacologic Considerations in the Disposition of Antibodies and Antibody-Drug Conjugates in Preclinical Models and in Patients Andrew T. Lucas 1,2,3,*, Ryan Robinson 3, Allison N. Schorzman 2, Joseph A. Piscitelli 1, Juan F. Razo 1 and William C. Zamboni 1,2,3 1 University of North Carolina (UNC), Eshelman School of Pharmacy, Chapel Hill, NC 27599, USA; [email protected] (J.A.P.); [email protected] (J.F.R.); [email protected] (W.C.Z.) 2 Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; [email protected] 3 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-919-966-5242; Fax: +1-919-966-5863 Received: 30 November 2018; Accepted: 22 December 2018; Published: 1 January 2019 Abstract: The rapid advancement in the development of therapeutic proteins, including monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs), has created a novel mechanism to selectively deliver highly potent cytotoxic agents in the treatment of cancer. These agents provide numerous benefits compared to traditional small molecule drugs, though their clinical use still requires optimization. The pharmacology of mAbs/ADCs is complex and because ADCs are comprised of multiple components, individual agent characteristics and patient variables can affect their disposition. To further improve the clinical use and rational development of these agents, it is imperative to comprehend the complex mechanisms employed by antibody-based agents in traversing numerous biological barriers and how agent/patient factors affect tumor delivery, toxicities, efficacy, and ultimately, biodistribution.
    [Show full text]
  • Modifications to the Harmonized Tariff Schedule of the United States to Implement Changes to the Pharmaceutical Appendix
    United States International Trade Commission Modifications to the Harmonized Tariff Schedule of the United States to Implement Changes to the Pharmaceutical Appendix USITC Publication 4208 December 2010 U.S. International Trade Commission COMMISSIONERS Deanna Tanner Okun, Chairman Irving A. Williamson, Vice Chairman Charlotte R. Lane Daniel R. Pearson Shara L. Aranoff Dean A. Pinkert Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Modifications to the Harmonized Tariff Schedule of the United States to Implement Changes to the Pharmaceutical Appendix Publication 4208 December 2010 (This page is intentionally blank) Pursuant to the letter of request from the United States Trade Representative of December 15, 2010, set forth at the end of this publication, and pursuant to section 1207(a) of the Omnibus Trade and Competitiveness Act, the United States International Trade Commission is publishing the following modifications to the Harmonized Tariff Schedule of the United States (HTS) to implement changes to the Pharmaceutical Appendix, effective on January 1, 2011. Table 1 International Nonproprietary Name (INN) products proposed for addition to the Pharmaceutical Appendix to the Harmonized Tariff Schedule INN CAS Number Abagovomab 792921-10-9 Aclidinium Bromide 320345-99-1 Aderbasib 791828-58-5 Adipiplon 840486-93-3 Adoprazine 222551-17-9 Afimoxifene 68392-35-8 Aflibercept 862111-32-8 Agatolimod
    [Show full text]
  • Antibody–Drug Conjugates
    Published OnlineFirst April 12, 2019; DOI: 10.1158/1078-0432.CCR-19-0272 Review Clinical Cancer Research Antibody–Drug Conjugates: Future Directions in Clinical and Translational Strategies to Improve the Therapeutic Index Steven Coats1, Marna Williams1, Benjamin Kebble1, Rakesh Dixit1, Leo Tseng1, Nai-Shun Yao1, David A. Tice1, and Jean-Charles Soria1,2 Abstract Since the first approval of gemtuzumab ozogamicin nism of activity of the cytotoxic warhead. However, the (Mylotarg; Pfizer; CD33 targeted), two additional antibody– enthusiasm to develop ADCs has not been dampened; drug conjugates (ADC), brentuximab vedotin (Adcetris; Seat- approximately 80 ADCs are in clinical development in tle Genetics, Inc.; CD30 targeted) and inotuzumab ozogami- nearly 600 clinical trials, and 2 to 3 novel ADCs are likely cin (Besponsa; Pfizer; CD22 targeted), have been approved for to be approved within the next few years. While the hematologic cancers and 1 ADC, trastuzumab emtansine promise of a more targeted chemotherapy with less tox- (Kadcyla; Genentech; HER2 targeted), has been approved to icity has not yet been realized with ADCs, improvements treat breast cancer. Despite a clear clinical benefit being dem- in technology combined with a wealth of clinical data are onstrated for all 4 approved ADCs, the toxicity profiles are helping to shape the future development of ADCs. In this comparable with those of standard-of-care chemotherapeu- review, we discuss the clinical and translational strategies tics, with dose-limiting toxicities associated with the mecha- associated with improving the therapeutic index for ADCs. Introduction in antibody, linker, and warhead technologies in significant depth (2, 3, 8, 9). Antibody–drug conjugates (ADC) were initially designed to leverage the exquisite specificity of antibodies to deliver targeted potent chemotherapeutic agents with the intention of improving Overview of ADCs in Clinical Development the therapeutic index (the ratio between the toxic dose and the Four ADCs have been approved over the last 20 years (Fig.
    [Show full text]
  • Refreshing the Biologic Pipeline 2020
    news feature Credit: Science Lab / Alamy Stock Photo Refreshing the biologic pipeline 2020 In the absence of face-to-face meetings, FDA and industry implemented regulatory workarounds to maintain drug and biologics approvals. These could be here to stay. John Hodgson OVID-19 might have been expected since 1996) — a small miracle in itself “COVID-19 confronted us with the need to severely impair drug approvals (Fig. 1 and Table 1). to better triage sponsors’ questions,” says Cin 2020. In the event, however, To the usual crop of rare disease and Peter Marks, the director of the Center for industry and regulators delivered a small genetic-niche cancer treatments, 2020 Biologics Evaluation and Research (CBER) miracle. They found workarounds and also added a chimeric antigen receptor at the FDA. “That was perhaps the single surrogate methods of engagement. Starting (CAR)-T cell therapy with a cleaner biggest takeaway from the pandemic related in January 2020, when the outbreak veered manufacturing process and the first to product applications.” Marks says that it westward, the number of face-to face approved blockbuster indication for a became very apparent with some COVID- meetings declined rapidly; by March, small-interfering RNA (siRNA) — the 19-related files that resolving a single they were replaced by Webex and Teams. European Medicines Agency’s (EMA) issue can help a sponsor enormously and (Secure Zoom meeting are to be added registration of the RNA interference accelerate the development cycle. Before this year.) And remarkably, by 31 December, (RNAi) therapy Leqvio (inclisiran) for COVID-19, it was conceivable that a small the US Food and Drug Administration cardiovascular disease.
    [Show full text]
  • Assessment Report
    28 January 2021 EMA/160756/2021 Committee for Medicinal Products for Human Use (CHMP) Assessment report Byfavo International non-proprietary name: remimazolam Procedure No. EMEA/H/C/005246/0000 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us An agency of the European Union Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 © European Medicines Agency, 2021. Reproduction is authorised provided the source is acknowledged. Table of contents List of abbreviations .................................................................................... 4 1. Background information on the procedure .............................................. 7 1.1. Submission of the dossier ...................................................................................... 7 1.2. Steps taken for the assessment of the product ......................................................... 8 2. Scientific discussion .............................................................................. 10 2.1. Problem statement ............................................................................................. 10 2.1.1. Disease or condition ......................................................................................... 10 2.1.2. Epidemiology .................................................................................................
    [Show full text]
  • Full Prescribing Information [FDA]
    HIGHLIGHTS OF PRESCRIBING INFORMATION -------------------------------CONTRAINDICATIONS------------------------------ These highlights do not include all the information needed to use None. MONJUVI safely and effectively. See full prescribing information for MONJUVI. ------------------------WARNINGS AND PRECAUTIONS----------------------- Infusion-Related Reactions: Monitor patients frequently during infusion. MONJUVI® (tafasitamab-cxix) for injection, for intravenous use Interrupt or discontinue infusion based on severity. (2.3, 5.1) Initial U.S. Approval: 2020 Myelosuppression: Monitor complete blood counts. Manage using dose modifications and growth factor support. Interrupt or discontinue -----------------------------INDICATIONS AND USAGE-------------------------- MONJUVI based on severity. (2.3, 5.2) MONJUVI is a CD19-directed cytolytic antibody indicated in combination Infections: Bacterial, fungal and viral infections can occur during and with lenalidomide for the treatment of adult patients with relapsed or following MONJUVI. Monitor patients for infections. (2.3, 5.3) refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, Embryo-Fetal Toxicity: May cause fetal harm. Advise females of including DLBCL arising from low grade lymphoma, and who are not eligible reproductive potential of the potential risk to a fetus and use of effective for autologous stem cell transplant (ASCT). contraception. (5.4) This indication is approved under accelerated approval based on overall -------------------------------ADVERSE
    [Show full text]
  • Pdf 792.82 K
    Review Article ...................................Trends in Pharmaceutical Sciences 2021: 7(2): 81-92. TIPS2020 FDA/EMA approvals for new immunotherapy drug technologies and applications Maryam Monajati1, Samira Sadat Abolmaali1,2,*, Ali Mohammad Tamaddon1,2 1Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran. 2Department of Pharmaceutical Nanotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran. ................................................................................................................................. Abstract Immunotherapy is a new approach applied in treatment of infections, autoimmune diseases, or cancer by activating or suppressing the immune system. Pre-clinical and clinical investigations on dis- covering new products with high efficacy and low side effects are still ongoing. Clinical studies revealed numerous advantages of immunotherapy over chemotherapy, including prolonged progression-free sur- vival and improved overall survival rate. However, immunotherapy may cause occasional severe adverse reactions due to an overactive immune system. This review gives an overview of new immunotherapeutic products approved by FDA/EMA in 2020. Moreover, the technologies used in manufacturing monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), and CAR-T cells are explained. In 2020, mAbs ap- proved for the first time in management of migraine, autoimmune CNS disease, and thyroid eye disorder. In addition, new ADC and CAR-T cell therapeutics
    [Show full text]
  • SEATTLE GENETICS, INC. (Exact Name of Registrant As Specified in Its Charter)
    Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2019 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number 0-32405 SEATTLE GENETICS, INC. (Exact name of registrant as specified in its charter) Delaware 91-1874389 (State or other jurisdiction of incorporation or organization) (I.R.S. Employer Identification No.) 21823 30th Drive SE Bothell, Washington 98021 (Address of principal executive offices, including zip code) (Registrant’s telephone number, including area code): (425) 527-4000 Securities registered pursuant to Section 12(b) of the Act: Title of class Trading Symbol(s) Name of each exchange on which registered Common Stock, par value $0.001 SGEN The Nasdaq Stock Market LLC Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐ Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).
    [Show full text]
  • Antibody–Drug Conjugates: the Last Decade
    pharmaceuticals Review Antibody–Drug Conjugates: The Last Decade Nicolas Joubert 1,* , Alain Beck 2 , Charles Dumontet 3,4 and Caroline Denevault-Sabourin 1 1 GICC EA7501, Equipe IMT, Université de Tours, UFR des Sciences Pharmaceutiques, 31 Avenue Monge, 37200 Tours, France; [email protected] 2 Institut de Recherche Pierre Fabre, Centre d’Immunologie Pierre Fabre, 5 Avenue Napoléon III, 74160 Saint Julien en Genevois, France; [email protected] 3 Cancer Research Center of Lyon (CRCL), INSERM, 1052/CNRS 5286/UCBL, 69000 Lyon, France; [email protected] 4 Hospices Civils de Lyon, 69000 Lyon, France * Correspondence: [email protected] Received: 17 August 2020; Accepted: 10 September 2020; Published: 14 September 2020 Abstract: An armed antibody (antibody–drug conjugate or ADC) is a vectorized chemotherapy, which results from the grafting of a cytotoxic agent onto a monoclonal antibody via a judiciously constructed spacer arm. ADCs have made considerable progress in 10 years. While in 2009 only gemtuzumab ozogamicin (Mylotarg®) was used clinically, in 2020, 9 Food and Drug Administration (FDA)-approved ADCs are available, and more than 80 others are in active clinical studies. This review will focus on FDA-approved and late-stage ADCs, their limitations including their toxicity and associated resistance mechanisms, as well as new emerging strategies to address these issues and attempt to widen their therapeutic window. Finally, we will discuss their combination with conventional chemotherapy or checkpoint inhibitors, and their design for applications beyond oncology, to make ADCs the magic bullet that Paul Ehrlich dreamed of. Keywords: antibody–drug conjugate; ADC; bioconjugation; linker; payload; cancer; resistance; combination therapies 1.
    [Show full text]
  • 1 Oncologic Drugs Advisory Committee (ODAC)
    Oncologic Drugs Advisory Committee (ODAC) Meeting April, 27, 2021 BLA# 761034/Supplement 18 Drug name: TECENTRIQ® (atezolizumab) Applicant: Genentech, Inc. Combined FDA and Applicant ODAC Briefing Document Advisory Committee Briefing Materials: Available For Public Release 1 DISCLAIMER STATEMENT The attached package contains background information prepared by the Applicant and the Food and Drug Administration (FDA) for the panel members of the advisory committee. The package contains assessments and/or conclusions and recommendations written by individual FDA reviewers. Such conclusions and recommendations do not necessarily represent the final position of the individual reviewers, nor do they necessarily represent the final position of the Review Division or Office. We have brought the drug TECENTRIQ® (also known as atezolizumab) to this Advisory Committee in order to gain the Committee’s insights and opinions, and the background package may not include all issues relevant to the final regulatory recommendation and instead is intended to focus on issues identified by the Agency for discussion by the advisory committee. The FDA will not issue a final determination on the issues at hand until input from the advisory committee process has been considered and all reviews have been finalized. The final determination may be affected by issues not discussed at the advisory committee meeting. 2 Table of Contents Table of Tables .........................................................................................................................
    [Show full text]
  • FDA Updates Highlighting the Latest Cancer Treatments
    FDA Updates Highlighting the Latest Cancer Treatments Orphan Drug Designation of NUV-422 for (mCRC) or squamous cell carcinoma of the head and neck (SCCHN). Malignant Gliomas This approval provides for a biweekly dosage regimen option in The FDA has granted Orphan Drug Designation to NUV-422, a cyclin- addition to the previously approved weekly dosage regimen for the dependent kinase (CDK) 2/4/6 inhibitor, for the treatment of patients approved indications when cetuximab is used as a single agent or in with malignant gliomas. combination with chemotherapy. Patient enrollment and dosing is ongoing in the Phase I/II study The approval was based on population pharmacokinetic (PK) of NUV-422 in adult patients with recurrent or refractory high-grade modeling analyses that compared the predicted exposures of cetux- gliomas, including glioblastoma multiforme. The Phase I dose-esca- imab 500 mg Q2W to observed cetuximab exposures in patients who lation part of the study is designed to evaluate safety and tolerability, received cetuximab 250 mg weekly. The application was also supported as well as determine a recommended Phase II dose based on the toler- by pooled analyses of overall response rates, progression-free survival, ability profile and pharmacokinetic properties of NUV-422. The Phase and overall survival (OS) from published literature in patients with II dose expansion part of the study is expected to initially focus on CRC and SCCHN, and OS analyses using real-world data in patients patients with high-grade gliomas, and it is designed to evaluate overall with mCRC who received either the weekly cetuximab or Q2W regi- response rate, duration of response, and survival.
    [Show full text]