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1
Gould, Stephen J. "AIDS and FDA Drug-Approved Policy:." Journal of Health & Social Policy 2, no. 2 (February 21, 1991): 39–46. http://dx.doi.org/10.1300/j045v02n02_03.
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Vokinger, Kerstin Noëlle, and Aaron S. Kesselheim. "Application of orphan drug designation to cancer treatments (2008–2017): a comprehensive and comparative analysis of the USA and EU." BMJ Open 9, no. 10 (October 2019): e028634. http://dx.doi.org/10.1136/bmjopen-2018-028634.
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ObjectiveTo determine differences in the characteristics of cancer drugs designated as orphan drugs by the Food and Drug Administration (FDA) and European Medicines Agency (EMA).Design and settingIdentification of all cancer drugs (initial or supplementary indication) with orphan status approved by the FDA between 2008–2017 based on publicly accessible reports. The European public assessment reports (EPAR) was searched to determine whether these FDA-approved drugs were also approved by the EMA.Main outcome measuresExtraction of active ingredient, trade name, approval date and approved indication from two FDA data sources (Orphan Drug Product Designation Database, Drugs@FDA) and comparison with the same data from EPAR.ResultsThe FDA approved 135 cancer drugs with orphan indications that met our inclusion criteria, of which 101 (75%) were also approved by the EMA. 80/101 (79%) were first approved in the USA. Only 41/101 (41%) also received orphan designation by the EMA. 33/101 (33%) were approved for biomarker-based indications in the USA, however, only nine approved cancer drug indications by the EMA were biomarker-derived drugs. 78% (47/60) of approved cancer drugs that were only approved in the USA with orphan status were indicated for solid tumours, 22% (13/60) had indications for non-solid tumours. By contrast, out of those approved cancer drugs that received orphan designation by both agencies, 20% (8/41) were indicated for solid, and 80% (33/41) for non-solid tumours.ConclusionsOrphan designation was intended to encourage drug development for rare conditions. This study shows that the FDA approves more cancer drugs with such designations compared with the EMA, especially for subgroups of more prevalent cancers. One reason for the difference could be that the European Union requires demonstration of significant benefit for drugs that target the same indication as a drug already on the market to earn the orphan designation.
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Zhong, Hao, Ging Chan, Yuanjia Hu, Hao Hu, and Defang Ouyang. "A Comprehensive Map of FDA-Approved Pharmaceutical Products." Pharmaceutics 10, no. 4 (December 6, 2018): 263. http://dx.doi.org/10.3390/pharmaceutics10040263.
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With the increasing research and development (R&D) difficulty of new molecular entities (NMEs), novel drug delivery systems (DDSs) are attracting widespread attention. This review investigated the current distribution of Food and Drug Administration (FDA)-approved pharmaceutical products and evaluated the technical barrier for the entry of generic drugs and highlighted the success and failure of advanced drug delivery systems. According to the ratio of generic to new drugs and the four-quadrant classification scheme for evaluating the commercialization potential of DDSs, the results showed that the traditional dosage forms (e.g., conventional tablets, capsules and injections) with a lower technology barrier were easier to reproduce, while advanced drug delivery systems (e.g., inhalations and nanomedicines) with highly technical barriers had less competition and greater market potential. Our study provides a comprehensive insight into FDA-approved products and deep analysis of the technical barriers for advanced drug delivery systems. In the future, the R&D of new molecular entities may combine advanced delivery technologies to make drug candidates into more therapeutically effective formulations.
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Ezeife, Doreen Anuli, Patricia Tang, Daniel Yick Chin Heng, and Stephen Welch. "Comparison of drug approval between health Canada (HC) and the U.S. Food and Drug Administration (FDA)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 6082. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.6082.
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6082 Background: Differences in drug approval processes between countries can impact patient access to new therapies. In Canada, patients can freely access a new treatment after regulatory approval by Health Canada (HC) followed by funding approval from the provincial government. The aims of this study were to delineate the Canadian drug approval timeline and to compare the time to drug approval between HC and the US FDA. Methods: Cancer drugs approved by the FDA from 1989 to 2011 were reviewed. For each drug, the following endpoints were determined: publication date of phase I and pivotal phase III trial, date of FDA and HC approval, HC submission date, and funding approval in Alberta (AB). Time intervals between the aforementioned endpoints were calculated. Results: Of 55 FDA-approved drugs, 51 drugs are approved by HC with 40 of these drugs funded in AB. HC approval occurs an average of 14.4 months post FDA approval (95% CI -36.9 to 66.1, sign rank test p<0.0001). However, there was no significant difference between the mean time from Phase I to FDA approval (48.5 months; 95% CI 21.2 to 75.8) and Phase I to HC approval (61.5 months; 95% CI 32.4 to 90.5). Most drugs (74%) were approved by the FDA prior to publication of the phase III trial. There was a trend towards faster drug approval from Phase III to FDA approval compared to HC (-14.97 versus 0.1 months, p = 0.05). HC submission occurs before FDA drug approval 77% of the time (mean 3.0 months prior; 95%CI: -59.1 to 43.4, p = 0.0206). HC approval occurs on average 17 months post HC submission. AB funding approval occurs on average 22 months after HC approval. The time interval from Phase I to AB funding approval was significantly shorter for targeted compared to cytotoxic agents (mean time 58 vs. 120 months; p = 0.039). Conclusions: HC drug approval lags behind FDA approval by about 14 months. Time from Phase III to drug approval tends to be shorter for the FDA compared to HC. This is the first documentation, to our knowledge, of the time required to bring a drug from phase I trial to provincial funding approval.
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Saberian, Nafiseh, Azam Peyvandipour, Michele Donato, Sahar Ansari, and Sorin Draghici. "A new computational drug repurposing method using established disease–drug pair knowledge." Bioinformatics 35, no. 19 (March 6, 2019): 3672–78. http://dx.doi.org/10.1093/bioinformatics/btz156.
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Abstract Motivation Drug repurposing is a potential alternative to the classical drug discovery pipeline. Repurposing involves finding novel indications for already approved drugs. In this work, we present a novel machine learning-based method for drug repurposing. This method explores the anti-similarity between drugs and a disease to uncover new uses for the drugs. More specifically, our proposed method takes into account three sources of information: (i) large-scale gene expression profiles corresponding to human cell lines treated with small molecules, (ii) gene expression profile of a human disease and (iii) the known relationship between Food and Drug Administration (FDA)-approved drugs and diseases. Using these data, our proposed method learns a similarity metric through a supervised machine learning-based algorithm such that a disease and its associated FDA-approved drugs have smaller distance than the other disease-drug pairs. Results We validated our framework by showing that the proposed method incorporating distance metric learning technique can retrieve FDA-approved drugs for their approved indications. Once validated, we used our approach to identify a few strong candidates for repurposing. Availability and implementation The R scripts are available on demand from the authors. Supplementary information Supplementary data are available at Bioinformatics online.
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Hershman, Dawn L., Alfred I. Neugut, Donna Buono, Catherine A. Richards, Sherry A. Glied, and Jason Dennis Wright. "Off-label and compendia use of chemotherapy in patients with metastatic cancer." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 6509. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.6509.
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6509 Background: In 2012, ASCO Identified opportunities to improve the quality and value of cancer care by reducing inappropriate and/or prolonged use of chemotherapy The NCCN compendium is recognized as an authoritative reference for insurance coverage for drug indications without FDA approval. We evaluated FDA-approved, compendia and unapproved use of chemotherapy. Methods: We useddata from the SEER-Medicare database to identify patients with metastatic cancer who received chemotherapy. For each tumor, drugs with >3 claims were identified. Each drug was classified as having an FDA-approved indication, an indication based on NCCN compendia guidelines or neither of these. The number of claims for each drug was calculated. Logistic regression was used to assess the factors that Results: Between 1998-2007, 37,351 subjects were identified as having received chemotherapy; of these, 24,876 (66.6%) received only FDA approved drugs, and 12,475 (33.4%) received at least one unapproved drug. Of those who received an unapproved drug, 8,669 (69%) received a drug with a compendia listing. Therefore, of the total population, 10% received a drug that was neither FDA nor compendia approved. The mean number of unapproved claims was 10.3 (SD=15.2) and the mean number of drugs was 1.3. Unapproved use was highest in subjects with prostate and lowest in patients with colon cancer. In a multivariate analysis, unapproved use decreased with increasing age and >2 comorbid conditions. Compared to prostate cancer, the odds of having an unapproved drug was lower for breast (OR=0.27), colon (OR=0.08), lung (OR=0.65), ovary (OR=0.38), uterus (OR=0.49) and myeloma (OR=0.60). No patients with colon or prostate cancer received compendia-approved drugs. Over 90% of unapproved use for breast, ovary and lung cancer were compendia-approved. Costs associated with unapproved/compendia use will be presented. Conclusions: A large fraction of patients who use chemotherapy receive FDA-unapproved drugs; however, the majority of those drugs are acknowledged by NCCN. A better understanding of the costs and benefits of compendia-approved drugs is warranted to reduce the costs of cancer care.
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Nair, Aathira Sujathan, Ashutosh Kumar Singh, Astik Kumar, Sunil Kumar, Sunitha Sukumaran, Vishal Payyalot Koyiparambath, Leena K. Pappachen, T. M. Rangarajan, Hoon Kim, and Bijo Mathew. "FDA-Approved Trifluoromethyl Group-Containing Drugs: A Review of 20 Years." Processes 10, no. 10 (October 11, 2022): 2054. http://dx.doi.org/10.3390/pr10102054.
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As people around the world regard 2020 as the year of COVID-19, the medical community considers this year to be the second-best year, shared with the year 1996, with respect to the number of drug molecules approved by the US Food and Drug Administration (FDA). Both years, 2020 and 1996, had a record of 53 new drug molecules approved by the FDA. In the year 2020, 53 new chemical entities and 13 biological medicines were approved, including 10 monoclonal antibodies, 2 antibody-drug conjugates, 3 peptides, and 2 oligonucleotides. Among them, most of the compounds were found to have fluorine or fluorine-containing functional groups exhibiting numerous pharmacological activities. Herein, we summarized the trifluoromethyl (TFM, -CF3)-group-containing FDA-approved drugs for the last 20 years. This article specially features and details the previous 20-year literature data, covering CF3-incorporated potential drug molecules, including their syntheses and uses for various diseases and disorders. The review covers the detailed chemistry of 19 FDA-approved drugs in the past 20 years, which contains the TFM group as one of the pharmacophores.
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Klasmeier, Coleen, and Martin H. Redish. "Off-Label Prescription Advertising, the FDA and the First Amendment: A Study in the Values of Commercial Speech Protection." American Journal of Law & Medicine 37, no. 2-3 (June 2011): 315–57. http://dx.doi.org/10.1177/009885881103700206.
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In order to protect the nation from harmful or worthless drugs and devices, the Food and Drug Administration (FDA or the Agency) is legislatively authorized to restrict the sale of prescription drugs or medical devices to those whose efficacy and safety have been reviewed and approved by the Agency. Drugs and devices are approved for a specific medical purpose. In numerous instances, however, the medical profession has discovered that treatments approved for one purpose may also serve other valuable medical purposes. Indeed, on a number of occasions such “off-label” treatments have proven to be essential to the successful treatment of some very serious illnesses.In these off-label situations, the FDA is faced with a dilemma. On the one hand, off-label use of prescription drug and devices gives rise to a series of major problems for the FDA. While the drug and devices in question have been vetted and approved by the FDA for their designated purpose, at no point has the FDA reviewed the supporting scientific data to determine efficacy for the off-label purpose.
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Losben, Nancy L. "2020: A Record Year for Drug Approvals." Senior Care Pharmacist 36, no. 4 (April 1, 2021): 174–75. http://dx.doi.org/10.4140/tcp.n.2021.174.
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In 2020 The United States Food and Drug Administration's (FDA) Center for Drug Evaluation and Research (CDER) approved 53 novel drugs, five more than in 2019, but still an aggressive number when compared with 2015 when only 45 new drugs were released to the market. CDER, the largest department within the FDA, has robustly approved a rising number of generic drugs in the last several years, increasing their accessibility and reducing patient and payor costs.
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Rizzo, Carla, Sara Amata, Ivana Pibiri, Andrea Pace, Silvestre Buscemi, and Antonio Palumbo Piccionello. "FDA-Approved Fluorinated Heterocyclic Drugs from 2016 to 2022." International Journal of Molecular Sciences 24, no. 9 (April 23, 2023): 7728. http://dx.doi.org/10.3390/ijms24097728.
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The inclusion of fluorine atoms or heterocyclic moiety into drug structures represents a recurrent motif in medicinal chemistry. The combination of these two features is constantly appearing in new molecular entities with various biological activities. This is demonstrated by the increasing number of newly synthesized fluorinated heterocyclic compounds among the Food and Drug Administration FDA-approved drugs. In this review, the biological activity, as well as the synthetic aspects, of 33 recently FDA-approved fluorinated heterocyclic drugs from 2016 to 2022 are highlighted.
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Kim, Jeeyun A., Rachel Ceccarelli, and Christine Y. Lu. "Pharmacogenomic Biomarkers in US FDA-Approved Drug Labels (2000–2020)." Journal of Personalized Medicine 11, no. 3 (March 4, 2021): 179. http://dx.doi.org/10.3390/jpm11030179.
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Pharmacogenomics (PGx) is a key subset of precision medicine that relates genomic variation to individual response to pharmacotherapy. We assessed longitudinal trends in US FDA approval of new drugs labeled with PGx information. Drug labels containing PGx information were obtained from Drugs@FDA and guidelines from PharmGKB were used to compare the actionability of PGx information in drug labels across therapeutic areas. The annual proportion of new drug approvals with PGx labeling has increased by nearly threefold from 10.3% (n = 3) in 2000 to 28.2% (n = 11) in 2020. Inclusion of PGx information in drug labels has increased for all clinical areas over the last two decades but most prominently for cancer therapies, which comprise the largest proportion (75.5%) of biomarker–drug pairs for which PGx testing is required. Clinically actionable information was more frequently observed in biomarker–drug pairs associated with cancer drugs compared to those for other therapeutic areas (n = 92 (59.7%) vs. n = 62 (40.3%), p < 0.0051). These results suggest that further evidence is needed to support the clinical adoption of pharmacogenomics in non-cancer therapeutic areas.
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Ceccoli, Stephen J. "Policy Punctuations and Regulatory Drug Review." Journal of Policy History 15, no. 2 (April 2003): 157–91. http://dx.doi.org/10.1353/jph.2003.0011.
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The FDA has dramatically decreased the regulatory review time for new drugs since the early 1990s. For example, according to the Tufts University Center for the Study of Drug Development (CSDD), which conducts triennial analyses of new drug approvals in the United States, the average FDA review time for approved New Chemical Entities (NCEs) decreased from 35.6 months in 1984–86 to 16.8 months in 1996–98. Thus, in a little more than a decade, the FDA has essentially cut its average review time in half. In addition to the declining review times, the agency's workload, as measured in terms of the number of drugs approved each year, also rose considerably in the 1990s. Specifically, the agency approved a total of 232 NCEs between 1993 and 1999, compared to just 163 approvals during the previous seven-year span—a 42 percent increase. Figures 1 and 2 illustrate the agency's decreased review times and increased workload, respectively. Thus, over the past decade the FDA has approved more drugs and done so in less time than at any other period in history. Simply stated, this change in regulatory performance, especially the declining review times, has been absolutely stunning.
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Gnanasakthy, Ari, Carla DeMuro, Marci Clark, Emily Haydysch, Esprit Ma, and Vijayveer Bonthapally. "Patient-Reported Outcomes Labeling for Products Approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014)." Journal of Clinical Oncology 34, no. 16 (June 1, 2016): 1928–34. http://dx.doi.org/10.1200/jco.2015.63.6480.
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Purpose To review the use of patient-reported outcome (PRO) data in medical product labeling granted by the US Food and Drug Administration (FDA) for new molecular entities and biologic license applications by the FDA Office of Hematology and Oncology Products (OHOP) between January 2010 and December 2014, to elucidate challenges faced by OHOP for approving PRO labeling, and to understand challenges faced by drug manufacturers to include PRO end points in oncology clinical trials. Methods FDA Drug Approval Reports by Month were reviewed to obtain the number of new molecular entities and biologic license applications approved from 2010 to 2014. Drugs approved by the FDA OHOP during this period were selected for further review, focusing on brand and generic name; approval date; applicant; indication; PRO labeling describing treatment benefit, measures, end point status, and significant results; FDA reviewer feedback on PRO end points; and study design of registration trials. First in class, priority review, fast track, orphan drug, or accelerated approval status was retrieved for selected oncology drugs from 2011 to 2014. Descriptive analyses were performed by using Microsoft Excel 2010. Results Of 160 drugs approved by the FDA (2010-2014), 40 were approved by OHOP. Three (7.5%) of the 40 received PRO-related labeling (abiraterone acetate, ruxolitinib phosphate, and crizotinib). Compared with nononcology drugs (2011-2014), oncology drugs were more likely to be orphan and first in class. The majority of oncology drug reviews by FDA were fast track, priority, or accelerated. Conclusion Although symptoms and functional decrements are common among patients with cancer, PRO labeling is rare in the United States, likely because of logistical hurdles and oncology study design. Recent developments within the FDA OHOP to capture PROs in oncology studies for the purpose of product labeling are encouraging.
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Chopra, S., M. Torres-Ortiz, L. Hokama, P. Madrid, M. Tanga, K. Mortelmans, K. Kodukula, and A. K. Galande. "Repurposing FDA-approved drugs to combat drug-resistant Acinetobacter baumannii." Journal of Antimicrobial Chemotherapy 65, no. 12 (September 22, 2010): 2598–601. http://dx.doi.org/10.1093/jac/dkq353.
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Desai, Bansri, Kyungwan Hong, John H. Powers, and Peter Doshi. "Reporting of Drug Benefit in FDA-Approved Prescription Drug Labeling." Journal of General Internal Medicine 35, no. 1 (October 28, 2019): 377–79. http://dx.doi.org/10.1007/s11606-019-05460-2.
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&NA;. "New anti-Parkinsonian drug approved by US FDA." Inpharma Weekly &NA;, no. 1095 (July 1997): 22. http://dx.doi.org/10.2165/00128413-199710950-00044.
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DeWitt, Sheila H., and Bruce E. Maryanoff. "Deuterated Drug Molecules: Focus on FDA-Approved Deutetrabenazine." Biochemistry 57, no. 5 (November 21, 2017): 472–73. http://dx.doi.org/10.1021/acs.biochem.7b00765.
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Wetzel, Carlie, Mitchell Lonneman, and Chun Wu. "Polypharmacological drug actions of recently FDA approved antibiotics." European Journal of Medicinal Chemistry 209 (January 2021): 112931. http://dx.doi.org/10.1016/j.ejmech.2020.112931.
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Do, Michael, Bona Shin, Elaina Lioudis, and Emaleigh Munn. "Novel Drugs Approved in 2021-2022." Transformative Medicine 1, no. 3 (September 2022): 72–77. http://dx.doi.org/10.54299/tmed/zcno1399.
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This article provides an abbreviated overview of the newly Federal Drug Administration (FDA)approved novel drugs of 2021-2022 with their respective approved indication(s). The FDA serves as the governing body that regularly evaluates and approves medications that will eventually be introduced to the market for routine use. These medications include both drugs that are the same or related to previously approved products (e.g., Extended indications of priorly approved medications) and novel drugs. By definition, a novel drug is an innovative product which serves to improve quality care in patient populations with unmet or advanced medical needs to overall advance patient care and public health. This article was employed to highlight medications that may be seen in practice and to heighten overall awareness of these new drugs. From January 1, 2021, through June 13, 2022, the FDA approved 66 drugs characterized as novel (Table 1). The four drugs highlighted in this article were selected based on potential inpatient and outpatient utility, disease-state prevalence, and overall innovative medicationbased treatment approaches. The four highlighted drugs are included in Table 2.
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Rodwin, Marc A. "Rooting Out Institutional Corruption to Manage Inappropriate Off-Label Drug Use." Journal of Law, Medicine & Ethics 41, no. 3 (2013): 654–64. http://dx.doi.org/10.1111/jlme.12075.
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The Food and Drug Administration (FDA) authorizes the marketing of a drug only for uses that the manufacturer has demonstrated to be safe and effective, based on evidence from at least two clinical trials. However, the FDA does not regulate the practice of medicine, so physicians may prescribe drugs in any manner they choose. Prescribing drugs in ways that deviate from the uses specified in the FDA-approved drug label, package insert, and marketing authorization is referred to as off-label prescribing. This occurs when physicians prescribe a drug for a therapeutic purpose other than the one approved by the FDA; treat patients in a different age cohort or gender than the population on which it was tested; or prescribe a different dose, for a different duration of use, or a different mode of administration than indicated on the label.
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Omae, Kenji, Yuki Kataoka, Yasushi Tsujimoto, Yusuke Tsutsumi, Shunichi Fukuhara, and Toshi Furukawa. "Publication statuses of clinical trials supporting immune checkpoint inhibitors recently approved by the United States Food and Drug Administration: A meta-epidemiological investigation." Journal of Clinical Oncology 37, no. 8_suppl (March 10, 2019): 89. http://dx.doi.org/10.1200/jco.2019.37.8_suppl.89.
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89 Background: The low trial publication rate for drugs approved by the U.S. Food and Drug Administration (FDA) and the discrepancies between data submitted to the FDA and data found in published trials remain concerning. We investigated the publication statuses of trials of recently approved anticancer drugs documented by the FDA, especially immune checkpoint inhibitors (ICPis), to determine the discrepancies between data submitted to the FDA and those published. Methods: We identified all ICPis approved between 2011 (the year the first ICPi was approved by the FDA) and 2014 (selected to assure a follow-up of at least 3 years post-approval). We assessed the clinical trials for each drug indication and matched each trial with publications in the literature. The primary outcome was the publication status 2 years post-approval. We examined the association between time to publication and drug type using a multilevel Cox regression model, adjusted for clustering within drug indications and individual covariates. Results: Between 2011 and 2014, 36 anticancer drugs including 3 ICPis were newly approved by the FDA. Of 19 trials investigating the 3 ICPis, 11 (58%) were published within 2 years post-approval. We randomly selected 10 of the 33 remaining anticancer drugs; 68 of 101 trials investigating these drugs (67%) were published. Overall, the publication rate was 66% at 2 years post-approval with a median time to publication of 2.3 years. There was no significant difference in time to trial publication between ICPis and other anticancer drugs (adjusted hazard ratio [HR], 1.1; 95% confidence interval [CI], 0.8–1.7; P = 0.55); however, non-ICPIs investigated specifically in randomized phase 2 or 3 trials were significantly more likely to be published earlier than ICPis (adjusted HR, 7.4; 95% CI, 1.8–29.5; P = 0.005). Conclusions: One in three trials of the newest anticancer drugs remained unpublished 2 years after FDA approval. The ICPi publication rate was similar to that of other anticancer drugs. (Protocol registration: UMIN000030475).
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Hamrell, Michael R., Marilyn N. Martinez, Shrikant V. Dighe, and Paul D. Parkman. "Bioequivalence of Generic Thioridazine Drug Products—The FDA Viewpoint." Drug Intelligence & Clinical Pharmacy 21, no. 4 (April 1987): 362–69. http://dx.doi.org/10.1177/106002808702100413.
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The phenothiazines are among the most widely used drugs to treat symptoms commonly associated with acute and chronic psychoses. One of the commonly prescribed compounds within this class of drugs is thioridazine, available both as a generic product as well as the innovator product, Mellaril. Each of these products is coded as bioequivalent and consequently therapeutically equivalent by the Food and Drug Administration (FDA). A recent issue of this journal contained an article that raised a number of questions concerning the bioequivalence of the generic versions of thioridazine that have been approved by the FDA. Their article was based in part on information obtained from the FDA as well as information supplied to the authors by Sandoz, Inc., the manufacturer of the original thioridazine drug product Mellaril. The FDA has reviewed its original decision of bioequivalence. Based on this reassessment, the FDA strongly rejects the assertion by the authors that several of the approved generic thioridazine products are not bioequivalent. The rationale behind the FDA decisions and the FDA's viewpoint on the bioequivalence of generic thioridazine drug products is discussed in detail.
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Goodman, Aaron M., Michael Choi, Matthew Wieduwilt, Carolyn Mulroney, Caitlin Costello, Garrett Frampton, Vincent Miller, and Razelle Kurzrock. "Next-Generation Sequencing Reveals Potentially Actionable Alterations in the Majority of Patients With Lymphoid Malignancies." JCO Precision Oncology, no. 1 (November 2017): 1–13. http://dx.doi.org/10.1200/po.16.00004.
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Purpose Next-generation sequencing (NGS) identifies potentially targetable alterations by US Food and Drug Administration (FDA)–approved drugs and/or by available experimental agents that may not have otherwise been contemplated. Many targeted drugs have been developed for diverse solid cancers; a smaller number of genomically targeted drugs have been approved for lymphoid malignancies. Materials and Methods We analyzed NGS results from 60 patients with various lymphoid malignancies and found 224 alterations (median per patient, three alterations). Results Forty-nine patients (82%) had potentially actionable alterations with the use of FDA-approved drugs and/or experimental therapies; only 11 patients (18%) had no theoretically actionable alterations. Only three patients (5%) had an alteration for which an approved drug in the disease is available (on label); 45 patients (75%) had an alteration for which an approved drug is available for another disease (off label). The median number of alterations per patient potentially actionable by an FDA-approved drug was one. Of note, 19 (32%) of 60 patients had intermediate to high tumor mutational burden, which may predict response to certain immunotherapy agents. Conclusion NGS identifies alterations that may be pharmacologically tractable in most patients with lymphoid malignancies, albeit with drugs that have usually been developed in the context of solid tumors. These observations merit expanded exploration in the clinical trials setting.
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Reddy, D. Samba, and Savitha Reddy. "The Novel Drugs of 2015 – An Extraordinary Growth of Innovative Pharmaceuticals." International Journal of Pharmaceutical Sciences and Nanotechnology 9, no. 4 (July 31, 2016): 3331–36. http://dx.doi.org/10.37285/ijpsn.2016.9.4.1.
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The FDA has approved 45 new drugs in 2015, a record approval in two decades, indicating another year of excellent innovation and productivity. There are many regulatory pathways at the FDA for the approval of novel drugs. Sixteen drugs (36%) were First-in-Class with a new or unique mechanism of action for treating a disease. About 29% of the new drugs are biologics. Moreover, 21 of 45 (47%) are orphan drugs for the treatment of rare diseases. The FDA approved many new drugs to treat various forms of cancer, urinary tract infections, chronic hepatitis C, cystic fibrosis, irritable bowel syndrome, heart failure, and high cholesterol, as well as the first approved reversal agent for a commonly-used blood thinner. For the second consecutive year, the FDA approved more “orphan” drugs for rare diseases than any previous year in recent history. From 2006 through 2014, the FDA averaged about 28 novel drug approvals per year. Such products represent innovation and provide important new therapies for patients worldwide. Despite such record new drug approvals, there is a continued productivity crisis in R&D due to a progressive rise in cost for drug discovery and development. The U.S. pharmaceutical market is forecasted to reach $548 billion by 2020. The prices appear to be increasing faster for generic and branded prescription drugs. Overall, faster development and regulatory review contributed to a spike in record approval of innovative pharmaceutical products in 2015
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Miller, Jennifer E., Marc Wilenzick, Nolan Ritcey, Joseph S. Ross, and Michelle M. Mello. "Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies." BMJ Open 7, no. 12 (December 2017): e017917. http://dx.doi.org/10.1136/bmjopen-2017-017917.
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ObjectivesTo define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs.DesignCross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies.Data sourcesData from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers.Outcome measuresTrial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level.ResultsThe FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%–100%) of trials in patients were registered, 71% (IQR 57%–100%) reported results or shared a CSR synopsis, 80% (70%–100%) were published and 96% (80%–100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%–100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries.ConclusionsAmong large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track companies’ transparency records and recognise exemplary companies may encourage further progress.
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Lindstrom, Jill A. "Sources of drug information: FDA-approved labeling and other official FDA sources." Dermatologic Therapy 22, no. 3 (May 2009): 246–56. http://dx.doi.org/10.1111/j.1529-8019.2009.01238.x.
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Monge, Andrea N., Daniel W. Sigelman, Robert J. Temple, and Harinder Singh Chahal. "Use of US Food and Drug Administration Expedited Drug Development and Review Programs by Orphan and Nonorphan Novel Drugs Approved From 2008 to 2021." JAMA Network Open 5, no. 11 (November 1, 2022): e2239336. http://dx.doi.org/10.1001/jamanetworkopen.2022.39336.
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ImportanceThe US Food and Drug Administration (FDA) has 4 programs that can be used alone or in combination to expedite drug availability: Accelerated Approval, Breakthrough Therapy, Fast Track, and Priority Review. Drugs using these programs can include novel drugs, which do not contain a previously FDA-approved active moiety, and orphan drugs, intended for diseases or conditions affecting fewer than 200 000 people; to date, no comprehensive evaluation of how these programs have been used in combination has been published.ObjectiveTo assess how often and in what combinations expedited programs are used in the development and review of approved novel biologics and small-molecule drugs, stratified by orphan drug status and indication.Design, Setting, and ParticipantsThis cross-sectional study evaluated all novel drugs that were FDA approved between January 1, 2008, and December 31, 2021.Main Outcomes and MeasuresThe main outcome was the frequency with which expedited programs were used and in what combinations, stratified by orphan drug status and drug type (small molecule vs therapeutic biologic). The unit of analysis was the novel drug–indication pair because a drug can be approved for multiple indications, each of which may use a different expedited program or differ in orphan drug status.ResultsThe study included 581 novel drug–indication pairs approved during the 14-year study period; 252 (43.4%) were orphan drugs, 139 (23.9%) were therapeutic biologics, and 442 (76.1%) were small-molecule drugs. Use of at least 1 expedited program increased from 11 of 26 drug-indication pairs (42.3%) in 2008 to 41 of 55 (74.5%) in 2021. Of the 363 approved drug-indication pairs using at least 1 expedited program, 225 (62.0%) were orphan drugs; at least 1 expedited program was used by 97 of the 139 approved biologic drugs (69.8%) and by 266 of the 442 approved small-molecule drugs (60.2%). Eighty-two of the 581 novel drug–indication pairs (14.1%) used the Accelerated Approval Program; of those, 65 (79.3%) were oncology drugs and 70 (85.4%) had an orphan designation.Conclusions and RelevanceThe study showed that use of the FDA’s expedited programs to bring novel drugs to market in the US increased from 2008 to 2021. The findings suggest that this trend is likely to continue.
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Gonzalez, Misty L. "New Drug Review-Ezogabine (Potiga): Seizing the seizure." Mental Health Clinician 1, no. 6 (December 1, 2011): 135–36. http://dx.doi.org/10.9740/mhc.n89803.
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Ezogabine was approved by the Food and Drug Administration (FDA) in June of 2011. This article reviews clinically significant aspects of this new drug including: the FDA-approved indications, mechanism of action, administration, drug interactions, adverse effects, clinical trial evidence, innovative properties and place in therapy.
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Sochacka-Ćwikła, Aleksandra, Marcin Mączyński, and Andrzej Regiec. "FDA-Approved Drugs for Hematological Malignancies—The Last Decade Review." Cancers 14, no. 1 (December 24, 2021): 87. http://dx.doi.org/10.3390/cancers14010087.
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Hematological malignancies, also referred to as blood cancers, are a group of diseases involving abnormal cell growth and persisting in the blood, lymph nodes, or bone marrow. The development of new targeted therapies including small molecule inhibitors, monoclonal antibodies, bispecific T cell engagers, antibody-drug conjugates, recombinant immunotoxins, and, finally, Chimeric Antigen Receptor T (CAR-T) cells has improved the clinical outcomes for blood cancers. In this review, we summarized 52 drugs that were divided into small molecule and macromolecule agents, approved by the Food and Drug Administration (FDA) in the period between 2011 and 2021 for the treatment of hematological malignancies. Forty of them have also been approved by the European Medicines Agency (EMA). We analyzed the FDA-approved drugs by investigating both their structures and mechanisms of action. It should be emphasized that the number of targeted drugs was significantly higher (46 drugs) than chemotherapy agents (6 drugs). We highlight recent advances in the design of drugs that are used to treat hematological malignancies, which make them more effective and less toxic.
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Taylor, Richard D., Malcolm MacCoss, and Alastair D. G. Lawson. "Combining Molecular Scaffolds from FDA Approved Drugs: Application to Drug Discovery." Journal of Medicinal Chemistry 60, no. 5 (December 23, 2016): 1638–47. http://dx.doi.org/10.1021/acs.jmedchem.6b01367.
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Gable, Kelly N. "New Drug Review: Lurasidone (Latuda®) - The new antipsychotic on the block." Mental Health Clinician 1, no. 6 (December 1, 2011): 131–32. http://dx.doi.org/10.9740/mhc.n89387.
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Lurasidone was approved by the Food and Drug Administration (FDA) in 2011. This article reviews clinically significant aspects of this new drug including: the FDA-approved indications, mechanism of action, administration, drug interactions, adverse effects, clinical trial evidence, innovative properties and place in therapy.
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Gable, Kelly N. "Saphris: Does a unique delivery system equal a unique drug?" Mental Health Clinician 1, no. 6 (December 1, 2011): 133–34. http://dx.doi.org/10.9740/mhc.n89388.
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Asenapine was approved by the Food and Drug Administration (FDA) in 2009. This article reviews clinically significant aspects of this new drug including: the FDA-approved indications, mechanism of action, administration, drug interactions, adverse effects, clinical trial evidence, innovative properties and place in therapy.
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Al Shaer, Danah, Othman Al Musaimi, Fernando Albericio, and Beatriz de la Torre. "2018 FDA Tides Harvest." Pharmaceuticals 12, no. 2 (April 5, 2019): 52. http://dx.doi.org/10.3390/ph12020052.
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In 2018, the United States Food and Drug Administration (FDA) approved a total of 59 new drugs, three of them (5%) are TIDES (or also, -tides), two oligonucleotides and one peptide. Herein, the three TIDES approved are analyzed in terms of medical target, mode of action, chemical structure, and economics.
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Kumar Shukla, Ajay, Kumar Shukla, Rekha Mehani, Swati Jain, and Sheema Maqsood. "Analysis of FDA Novel Drug Approvals." Biomedical and Pharmacology Journal 14, no. 1 (March 28, 2021): 225–33. http://dx.doi.org/10.13005/bpj/2117.
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Background: United States Food and Drug Administration (FDA) is the fastest drug review agency in the world. FDA is responsible for the protection of public health by assuring that foods are safe, wholesome, sanitary and, properly labeled. Novel drug Approvals are usually innovative products to serve unmet medical needs or otherwise help to advance patient care. Methods: FDA novel drug approvals were analyzed from calendar year (CY) 2012 to 2018 based on not only their numbers but also BASED ON their impact, innovation, access, and predictability. Results: The total number of novel drugs approved from CY 2012 to 2018 was 279 (average 40 novel drugs/ year). Impact of novel drug approvals: 50% were first in class and 43% were for rare diseases. Overall expedited development and review methods were used in 63% of the novel drug approvals. Access of novel drug approvals: 84% were first-cycle approval, 74% were approved in the US before other countries, 58% priority reviews among novel drug approvals. Predictability of novel drug approvals: 98% approvals able to meet PDUFA goal dates for application review. Conclusions: Novel drug approvals during CY 2012-2018 had a high quality which is very much evident by their high impact, good access, and high predictability.
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Huey, Ryan, Seerat Anand, Jane Elizabeth Rogers, Arvind Dasari, Gauri Rajani Varadhachary, Anirudh Gothwal, Jonathan M. Loree, Lee M. Ellis, Michael J. Overman, and Kanwal Pratap Singh Raghav. "Value appraisal of FDA approved cancer drugs over the past decade." Journal of Clinical Oncology 37, no. 27_suppl (September 20, 2019): 115. http://dx.doi.org/10.1200/jco.2019.37.27_suppl.115.
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115 Background: Value based drug pricing is emerging as an imperative health care precept in recognition of the ever-increasing drug costs, especially in oncology. Though novel therapies are regularly approved based on benefit, they are often associated with physical and financial toxicities to patients. We aimed to assess the value of FDA approved oncology drugs defined as their expected clinical benefit compared to their toxicities and costs. Methods: We reviewed all new cancer drug approvals by the FDA from 7/2008-6/2018. Current analysis was restricted to approvals based on overall survival (OS) and progression-free survival (PFS). Data regarding approval indication, effect size, and toxicity were collected from FDA website and publications. Toxicity was estimated as adverse events ≥ grade 3 (or serious adverse events) as reported. Micromedex RED BOOK was used to estimate the total drug price using 2018 average wholesale prices. Price was estimated over 3 months to account for difference in drug regimens. Results: Among the 231 trials used by FDA for approvals in oncology, 115 had OS or PFS as their primary endpoint. Median patients per trial was 539. Of 79 trials with a PFS endpoint, the median HR was 0.50 (range: 0.15 - 0.91); median 3-month drug price was $45,903.72. Compared to the control arm, median toxicity for new drugs was 7% higher (range: -34.4 - 55%). Correlation of HR benefit to 3-month price was 0.06 (95% CI: -0.17 - 0.28, P = 0.61). Correlation of net toxicities to 3-month price was 0.01 (95% CI: -0.25 - 0.26, P = 0.94). Of 43 trials with an OS endpoint, the median HR was 0.72 (range: 0.37 - 0.94); median 3-month price was $43,523.46. Relative to control arm, median toxicity for new drugs was 4% higher (range: -34.4 - 45.8%). Correlation of HR benefit to 3-month price was 0.38 (95% CI: 0.08 - 0.62, P = 0.012). Correlation of net toxicities to 3-month price was -0.12 (95% CI: -0.45 - 0.24, P = 0.50). Conclusions: Drug approvals in oncology come with a high cost and drug prices have very little correlation with estimated benefit in outcomes and toxicities. As policies evolve to promote higher value in health care, attention should be paid to benefits of drugs in relation to pricing and using biomarker-based patient selection to maximize benefits and minimize toxicities.
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Huey, Ryan, Seerat Anand, Jane Rogers, Arvind Dasari, Gauri Rajani Varadhachary, Anirudh Gothwal, Jonathan M. Loree, Lee M. Ellis, Michael J. Overman, and Kanwal Pratap Singh Raghav. "Value appraisal of FDA approved cancer drugs over the past decade." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e18385-e18385. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e18385.
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e18385 Background: Value based drug pricing is emerging as an imperative health care precept in recognition of the ever-increasing drug costs, especially in oncology. Though novel therapies are regularly approved based on benefit, they are often associated with physical and financial toxicities to patients. We aimed to assess the value of FDA approved oncology drugs defined as their expected clinical benefit compared to their toxicities and costs. Methods: We reviewed all new cancer drug approvals by the FDA from 7/2008-6/2018. Current analysis was restricted to approvals based on overall survival (OS) and progression-free survival (PFS). Data regarding approval indication, effect size, and toxicity were collected from FDA website and publications. Toxicity was estimated as adverse events ≥ grade 3 (or serious adverse events) as reported. Micromedex RED BOOK was used to estimate the total drug price using 2018 average wholesale prices. Price was estimated over 3 months to account for difference in drug regimens. Results: Among the 231 trials used by FDA for approvals in oncology, 115 had OS or PFS as their primary endpoint. Median patients per trial was 539. Of 79 trials with a PFS endpoint, the median HR was 0.50 (range: 0.15 - 0.91); median 3-month drug price was $45,903.72. Compared to the control arm, median toxicity for new drugs was 7% higher (range: -34.4 - 55%). Correlation of HR benefit to 3-month price was 0.06 (95% CI: -0.17 - 0.28, P = 0.61). Correlation of net toxicities to 3-month price was 0.01 (95% CI: -0.25 - 0.26, P = 0.94). Of 43 trials with an OS endpoint, the median HR was 0.72 (range: 0.37 - 0.94); median 3-month price was $43,523.46. Relative to control arm, median toxicity for new drugs was 4% higher (range: -34.4 - 45.8%). Correlation of HR benefit to 3-month price was 0.38 (95% CI: 0.08 - 0.62, P = 0.012). Correlation of net toxicities to 3-month price was -0.12 (95% CI: -0.45 - 0.24, P = 0.50). Conclusions: Drug approvals in oncology come with a high cost and drug prices have very little correlation with estimated benefit in outcomes and toxicities. As policies evolve to promote higher value in health care, attention should be paid to benefits of drugs in relation to pricing and using biomarker-based patient selection to maximize benefits and minimize toxicities.
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Holmes, Jamie, and Robin Hieber. "New Drug Review: Clobazam (Onfi®) - A “new” anticonvulsant option." Mental Health Clinician 1, no. 6 (December 1, 2011): 126–27. http://dx.doi.org/10.9740/mhc.n89385.
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Clobazam was approved by the Food and Drug Administration (FDA) in October of 2011. This article reviews clinically significant aspects of this new drug including: the FDA-approved indications, mechanism of action, administration, drug interactions, adverse effects, clinical trial evidence, innovative properties and place in therapy.
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Newton, Uma, and Tiffany-Jade Kreys. "Iloperidone (Fanapt®): Fan or not?" Mental Health Clinician 1, no. 6 (December 1, 2011): 137–39. http://dx.doi.org/10.9740/mhc.n89390.
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Iloperidone was approved by the Food and Drug Administration (FDA) in May of 2009. This article reviews clinically significant aspects of this new drug including: the FDA-approved indications, mechanism of action, administration, drug interactions, adverse effects, clinical trial evidence, innovative properties and place in therapy.
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Werremeyer, Amy B. "New Drug Review: Gabapentin enacarbil extended release (Horizant™) – A new formulation on the horizon." Mental Health Clinician 1, no. 6 (December 1, 2011): 128–30. http://dx.doi.org/10.9740/mhc.n89391.
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Gabapentin enacarbil was approved by the Food and Drug Administration (FDA) in April of 2011. This article reviews clinically significant aspects of this new drug including: the FDA-approved indications, mechanism of action, administration, drug interactions, adverse effects, clinical trial evidence, innovative properties and place in therapy.
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Gonzalez, Misty L. "Viibryd (Vilazodone): Viable option or for the byrds?" Mental Health Clinician 1, no. 6 (December 1, 2011): 140–41. http://dx.doi.org/10.9740/mhc.n89810.
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Vilazodone was approved by the Food and Drug Administration (FDA) in January of 2011. This article reviews clinically significant aspects of this new drug including: the FDA-approved indications, mechanism of action, administration, drug interactions, adverse effects, clinical trial evidence, innovative properties and place in therapy.
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Chancey, Rebecca J., Yon Yu, Patricia Yu, Julian Jolly, and Susan Montgomery. "770. Otherwise Unavailable Non-Malarial Parasitic Disease Treatment Drugs in the United States: an Update from CDC Parasitic Diseases Drug Service." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S429—S430. http://dx.doi.org/10.1093/ofid/ofaa439.960.
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Abstract Background The Centers for Disease Control and Prevention’s (CDC) support to clinicians includes providing access to certain drugs exclusively available through CDC for diseases that lack, or have limited market availability of, FDA-approved therapeutics in the U.S. These drugs are provided by CDC under expanded access Investigational New Drug (IND) applications, authorized by the FDA, to treating physicians. The CDC Parasitic Diseases Drug Service provides treatment drugs for patients with parasitic diseases, including travelers, immigrants and refugees from endemic countries. Methods CDC’s records for patients for whom drug was released over a 10-year period were reviewed. Results From 2010–2019, the annual number of drug releases for patient treatment ranged from 21–113 (median 99). Benznidazole, a treatment for Chagas disease, was the most common drug released for patients between 2012–2018, ranging from 42–63% of total drug releases annually. Sodium stibogluconate (Pentostam® 1), for treatment of certain presentations of cutaneous, visceral, and mucocutaneous leishmaniasis, accounted for 6–22% of annual releases over the last 10 years. While requests for treatment for human African trypanosomiasis are rare, in 2019 CDC released eflornithine and nifurtimox for one patient who met criteria for treatment according to the 2019 WHO recommendations.2 Conclusion Recent changes to release frequency of triclabendazole, benznidazole, nifurtimox, and sodium stibogluconate are likely due to FDA-approval and commercial availability of previously investigational drugs. Triclabendazole is now FDA approved for treatment of Fasciola infection in persons ≥6 years old and benznidazole is now FDA approved for treatment of Chagas disease in children 2–12 years old. Miltefosine has also been approved by FDA for treatment of certain leishmaniasis infections. CDC has successfully pursued expiry extensions of drugs with manufacturers, FDA, and other partners to ensure continued domestic availability of treatment options when there has been no or limited production of newer lots. CDC’s Parasitic Diseases Branch can be reached by telephone: 404-718-4745 or email: parasites@cdc.gov. 1 Pentostam® is made by GlaxoSmithKline 2 WHO interim guidelines for treatment of gambiense HAT. Geneva: 2019. Disclosures All Authors: No reported disclosures
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AKERMI, SARRA, Neha Lohar, Subrata Sinha, Surabhi Johari, Sunil Jayant, and Anshul Nigam. "In-silico identification of natural antiviral drug against SARS-CoV-2 and comparison with potential FDA approved drug targets." Journal of Science 3, no. 4 (September 5, 2020): 1–11. http://dx.doi.org/10.47944/jos.3.4.2020.1.
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Antimalarial drugs Chloroquine and Hydroxychloroquine have garnered most attention recently as a successful remedy for COVID19. However, the use of these drugs is still questionable due to its undetermined efficacy and side effects. The present study utilizes in-silico high throughput screening of FDA approved antiviral compounds and secondary plant metabolites against spike protein of novel coronavirus (SARS-CoV-2). This target was chosen because it is instrumental in entry of virus into human cells. It is observed that the plant compound Tocopheryl-curcumin has more affinity for spike protein of SARS-CoV-2 in comparison to the majority of FDA approved drugs. Tocopheryl-curcumin binds with the binding site of RBD domain of spike protein (6VSB, chain A) with free energy (∆G) of binding of -11.20 kcal/mol and makes strong hydrogen bonds with amino acid residues of S366, V367, L368, S373, and K529. Among the FDA approved drugs, Pibrentasvir obtains top rank with free energy (∆G) of binding of -9.69 kcal/mol. whereas; surprisingly Chloroquine (-6.87 kcal/mol) and Hydroxychloroquine (-7.24 kcal/mol) ranked lower in our docking study. The toxicity prediction by VEGA predicts that tocopheryl-curcumin shows no toxicity as compared to FDA approved drugs. Therefore, we infer that the plant-based tocopheryl-curcumin could be considered as potential and safer drug against COVID 19 disease as compared to chemical based drugs.
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Vokinger, Kerstin Noëlle, Paola Daniore, Thomas J. Hwang, ChangWon C. Lee, and Aaron S. Kesselheim. "Pivotal trial endpoints and prices of cancer drugs in the US and Europe." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 2077. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.2077.
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2077 Background: A key clinical outcome for new cancer drugs is improvement in overall survival (OS), defined as time from the date of randomization to the death from any cause. However, many cancer drugs are approved by regulators based on changes to surrogate measures of OS, such as progression-free survival or overall response rate. When surrogate measures are not validated, they can provide misleading information about drug efficacy. We categorized pivotal trial endpoints for recently-approved cancer drugs in the US and Europe as showing improvements in OS vs non-OS surrogates, and evaluated the correlation with drug prices. Methods: We identified new drugs FDA-approved between 2009 and 2018 that were indicated to treat solid and hematologic tumors in adults and that had also been approved by the EMA and Swissmedic by December 2019. Launch prices were extracted and adjusted to average sales prices for monthly treatment costs in the US and compared to currency-adjusted ex-factory monthly treatment costs in Germany, Switzerland, and England. Pivotal clinical trial primary endpoints were collected from the drug labeling and FDA medical reviews for the US, and the EMA public assessment reports for Europe, and categorized as OS in any trial vs. not. Pearson’s correlation tests assessed the association between launch prices and OS vs non-OS endpoints in each country. Results: 54 drugs were approved by the FDA, EMA, and Swissmedic during the study period. In the US, 30 (56%) were approved based on OS by contrast to 35 (65%) in the EMA. The number of cancer drugs approved by the FDA based on OS decreased in the past years. By contrast, the number of approved cancer drugs by the EMA based on OS were stable. There was no association for the US (p = 0.05), Germany (p = 0.13) and England (p = 0.12), while Switzerland revealed an association (p = 0.03) between OS endpoint and price. Conclusions: Reductions in use of OS endpoints as the basis for cancer drug approval in the US is concerning. Drug pricing should be better aligned with the benefit that drugs provide to patients, as measured by clinical trial outcomes such as OS.
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Shabir, Ghulam, Aamer Saeed, Wajeeha Zahid, Fatima Naseer, Zainab Riaz, Nafeesa Khalil, Muneeba, and Fernando Albericio. "Chemistry and Pharmacology of Fluorinated Drugs Approved by the FDA (2016–2022)." Pharmaceuticals 16, no. 8 (August 15, 2023): 1162. http://dx.doi.org/10.3390/ph16081162.
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Fluorine is characterized by high electronegativity and small atomic size, which provide this molecule with the unique property of augmenting the potency, selectivity, metabolic stability, and pharmacokinetics of drugs. Fluorine (F) substitution has been extensively explored in drug research as a means of improving biological activity and enhancing chemical or metabolic stability. Selective F substitution onto a therapeutic or diagnostic drug candidate can enhance several pharmacokinetic and physicochemical properties such as metabolic stability and membrane permeation. The increased binding ability of fluorinated drug target proteins has also been reported in some cases. An emerging line of research on F substitution has been addressed by using 18F as a radiolabel tracer atom in the extremely sensitive methodology of positron emission tomography (PET) imaging. This review aims to report on the fluorinated drugs approved by the US Food and Drug Administration (FDA) from 2016 to 2022. It cites selected examples from a variety of therapeutic and diagnostic drugs. FDA-approved drugs in this period have a variety of heterocyclic cores, including pyrrole, pyrazole, imidazole, triazole, pyridine, pyridone, pyridazine, pyrazine, pyrimidine, triazine, purine, indole, benzimidazole, isoquinoline, and quinoline appended with either F-18 or F-19. Some fluorinated oligonucleotides were also authorized by the FDA between 2019 and 2022.
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Beinse, Guillaume, Virgile Tellier, Valentin Charvet, Eric Deutsch, Isabelle Borget, Christophe Massard, Antoine Hollebecque, and Loic Verlingue. "Prediction of Drug Approval After Phase I Clinical Trials in Oncology: RESOLVED2." JCO Clinical Cancer Informatics, no. 3 (December 2019): 1–10. http://dx.doi.org/10.1200/cci.19.00023.
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PURPOSE Drug development in oncology currently is facing a conjunction of an increasing number of antineoplastic agents (ANAs) candidate for phase I clinical trials (P1CTs) and an important attrition rate for final approval. We aimed to develop a machine learning algorithm (RESOLVED2) to predict drug development outcome, which could support early go/no-go decisions after P1CTs by better selection of drugs suitable for further development. METHODS PubMed abstracts of P1CTs reporting on ANAs were used together with pharmacologic data from the DrugBank5.0 database to model time to US Food and Drug Administration (FDA) approval (FDA approval-free survival) since the first P1CT publication. The RESOLVED2 model was trained with machine learning methods. Its performance was evaluated on an independent test set with weighted concordance index (IPCW). RESULTS We identified 462 ANAs from PubMed that matched with DrugBank5.0 (P1CT publication dates 1972 to 2017). Among 1,411 variables, 28 were used by RESOLVED2 to model the FDA approval-free survival, with an IPCW of 0.89 on the independent test set. RESOLVED2 outperformed a model that was based on efficacy/toxicity (IPCW, 0.69). In the test set at 6 years of follow-up, 73% (95% CI, 49% to 86%) of drugs predicted to be approved were approved, whereas 92% (95% CI, 87% to 98%) of drugs predicted to be nonapproved were still not approved (log-rank P < .001). A predicted approved drug was 16 times more likely to be approved than a predicted nonapproved drug (hazard ratio, 16.4; 95% CI, 8.40 to 32.2). CONCLUSION As soon as P1CT completion, RESOLVED2 can predict accurately the time to FDA approval. We provide the proof of concept that drug development outcome can be predicted by machine learning strategies.
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Khaki, Ali Raza, Aakash Desai, Martin W. Schoen, Bishal Gyawali, Eddy J. Chen, Peter C. Yang, and Jeremy Lyle Warner. "Timing of US Food and Drug Administration (FDA) cancer drug approvals relative to publication of clinical trial results." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 2071. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.2071.
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2071 Background: Publication of clinical trial results in peer reviewed literature is essential to inform clinicians regarding the use of new anti-cancer treatments, which often have a low therapeutic ratio and require careful assessment of risks and benefits. Publication of registration trials should precede FDA approval to facilitate evaluation and implementation of new therapies. The timing of trial publication relative to FDA drug approvals has not been systematically investigated. Methods: We collected all FDA drug approvals for a cancer indication between 2000-19. Trials were identified using FDA labels as well as drugs and publications indexed on HemOnc.org. Approvals for generics/biosimilars, non-oncology indications and label revisions without supportive evidence were excluded. Dates of approval, the approval pathway, approval type (new vs expansion), and the first full publication related to the registration were recorded. Trials and approvals were matched using available metadata. We calculated the proportion of drugs approved prior to publication overall and for those receiving accelerated approval (AA). We used logistic regression to compare rates of pre-publication approval by approval pathway and by new vs expanded approval. Results: Among a total of 378 drug approvals, 139 (37%) had pre-publication approval. Of these, the median overall time from approval to publication was 140 days (IQR 64-281 days). For those with approval after publication, median time from publication to approval was 157 days (IQR 72-359 days). The number of drugs approved pre-publication rose by 27% between the first and last quarters of the study period, though, the proportion decreased as more anti-cancer drugs have been approved in recent years (Table). More drugs were approved pre-publication through AA than regular approval (46% vs 34%, OR 1.66 [95% CI 1.03-2.70], p=0.04) and as new approvals vs. expanded approvals (45% vs 32%, OR 1.76 [95% CI 1.15-2.70], p=0.01). Conclusions: A substantial minority of FDA approvals occur before trial results are published, with the odds being higher for drugs receiving AA and for new approvals. Since clinicians rely upon published results to inform risk/benefit decisions, efforts are needed to ensure trial results are published by the time of FDA approval of new cancer drugs and indications. [Table: see text]
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Chen, Charles H., and Timothy K. Lu. "Development and Challenges of Antimicrobial Peptides for Therapeutic Applications." Antibiotics 9, no. 1 (January 13, 2020): 24. http://dx.doi.org/10.3390/antibiotics9010024.
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More than 3000 antimicrobial peptides (AMPs) have been discovered, seven of which have been approved by the U.S. Food and Drug Administration (FDA). Now commercialized, these seven peptides have mostly been utilized for topical medications, though some have been injected into the body to treat severe bacterial infections. To understand the translational potential for AMPs, we analyzed FDA-approved drugs in the FDA drug database. We examined their physicochemical properties, secondary structures, and mechanisms of action, and compared them with the peptides in the AMP database. All FDA-approved AMPs were discovered in Gram-positive soil bacteria, and 98% of known AMPs also come from natural sources (skin secretions of frogs and toxins from different species). However, AMPs can have undesirable properties as drugs, including instability and toxicity. Thus, the design and construction of effective AMPs require an understanding of the mechanisms of known peptides and their effects on the human body. This review provides an overview to guide the development of AMPs that can potentially be used as antimicrobial drugs.
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Reddy, Neha K., Jason Roszik, David Carl Norris, Roman Groisberg, Niamh Coleman, Omar Alhalabi, Ethan B. Ludmir, Cullen M. Taniguchi, Ishwaria Mohan Subbiah, and Vivek Subbiah. "Dosing, drug reduction, drug interruption, and drug discontinuation rates among U.S. FDA approved tyrosine kinase inhibitors." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 3112. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.3112.
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3112 Background: The advent of tyrosine kinase inhibitors (TKIs) has altered the therapeutic landscape of multiple hematological and solid malignancies. FDA approved starting doses of TKIs are based on the recommended phase 2 dose (RP2D) in clinical trials. Since many of these drugs are continuously dosed, ongoing toxicities may lead to drug reductions and drug discontinuations. Hence in practice, many patients are started on lower doses due to tolerability concerns or are dose-reduced subsequently for toxicity. Herein, we assessed the dosing, drug reduction rates, and drug discontinuation rates among FDA approved TKIs. Methods: We established a database of all FDA approved TKIs from the FDA online label repository. We extracted descriptive data for indications and usage, type of approval, approval dosage, dose reduction recommendation, median age, dose reduction rates, drug discontinuation rates, dose modification, warnings, adverse reactions, clinical trial experience, and geriatric use above 65 yrs and 75 yrs. Results: TKIs were approved for 143 different indications, ranging from 1 indication to 11 indications (eg. Imatinib) from data arising from 7 patients to 2816 patients for a specific indication. Among all TKIs, median dose was 150 mg and average dose was 237 mg; 34 (23.8%) were approved bid vs 71 (49.7%) qd. Specifically for oncology, 54 indications were biomarker based (eg. EGFR mutant NSCLC) and 52 were non-biomarker based for specific diseases (eg. metastatic RCC). Among approved indications range of dose reduction rate (DRR), drug interruption rates (DIR), drug discontinuations rates (DDR) were 0.80-89%, 3%-89%, and 1-39% respectively. Most common reasons for DRR, DIR, and DDR were diarrhea, fatigue, nausea, vomiting, hepatotoxicity, rash, and hypertension. Geriatric use was listed in 99 indications ( > 65 yrs, 6-68%; > 75 yrs, 0.50-24%). Patient reported outcomes were not available. Conclusions: TKIs have a variable dose reduction and drug discontinuation rate. Clinical trials should evaluate multiple dosing regimens and schedules to lessen the toxicity burden and improve QOL in patients. Future studies are warranted to look into flat dosing vs alternative dosing, like weight-based dosing for TKIs, and to report patient reported outcomes.
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Rodriguez-Monguio, Rosa, Enrique Seoane-Vazquez, and John H. Powers. "A Comparative Assessment of Approvals and Discontinuations of Systemic Antibiotics and Other Therapeutic Areas." Healthcare 11, no. 12 (June 15, 2023): 1759. http://dx.doi.org/10.3390/healthcare11121759.
Full textAbstract:
Since 1980, the US Congress has passed legislation providing several incentives to encourage the development and regulatory approval of new drugs, particularly antibiotics. We assessed long-term trends and characteristics of approvals and discontinuations of all new molecular entities, new therapeutic biologics, and gene and cell therapies approved by the US Food and Drug Administration (FDA), as well as reasons for discontinuations by therapeutic class, in the context of laws and regulations implemented over the past four decades. In the period 1980–2021, the FDA approved 1310 new drugs, of which 210 (16.0%) had been discontinued as of 31 December 2021, including 38 (2.9%) withdrawn for safety reasons. The FDA approved 77 (5.9%) new systemic antibiotics, of which 32 (41.6%) had been discontinued at the end of the observation period, including 6 (7.8%) safety withdrawals. Since the enactment of the FDA Safety and Innovation Act in 2012, which created the Qualified Infectious Disease Product designation for antiinfectives to treat serious or life-threatening diseases due to resistant or potentially resistant bacteria, the FDA has approved 15 new systemic antibiotics, all using non-inferiority trials, for 22 indications and five different infections. Only one of the infections had labeled indications for patients with drug-resistant pathogens.
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Vadola, Lisa Ambrosini, Monique A. Pond, Ann Winter-Vann, and Robin Whitsell. "Faster approvals?: Trends in the use of FDA’s expedited approval programs for oncology medications." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e18270-e18270. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e18270.
Full textAbstract:
e18270 Background: With the importance of speed-to-market and addressing unmet needs, pharmaceutical companies have sought accelerated approvals through the Food and Drug Administration (FDA). Introduced with the FDA Safety and Innovation Act (FDASIA) of 2012, Breakthrough Therapy Designation (BTD) has become an important mechanism for approval of serious and life-threatening conditions that do not have adequate therapies. Notably, these pathways have been ill-understood by both pharmaceutical companies and health care providers. This study assessed how BTD and other FDA designations have played a role in the approval of oncology drug marketing applications and evaluated trends in the use of these regulatory pathways. Methods: We analyzed publicly available data on novel oncology drug approvals by the FDA from 2012-2016, including the 4 expedited programs for serious conditions (BTD, Accelerated Approval, Fast Track, and Priority Review). Results: Of the 43 novel oncology drugs approved by the FDA between 2012-2016, 42 used at least 1 of the expedited approval programs, including 65% that used ≥2 programs and 35% that used ≥3 programs. The BTD has been used by 15 of the 43 (35%) approved novel oncology drugs since 2012. The use of the BTD, Accelerated Approval pathway, and Priority Review designation among approved oncology drugs has generally increased each year from 2012-2016, while the use of the Fast Track designation has decreased over the same time period. Conclusions: Companies seeking oncology approvals often use more than one expediting strategy. Alone or in combinations, the BTD, Accelerated Approval, and Priority Review have been shown to play an increasingly important role in oncology drug development. Data collected between 2012-2016 suggest that use of BTD is growing more common, while use of the Fast Track designation has decreased among approved oncology drugs. Additional expedited approval programs have remained steady or increased since the FDA introduced BTD. Based on these observations, we anticipate use of the BTD, Accelerated Approval, and Priority Review designation will grow in future oncology drug applications.