Luspatercept in the treatment of lower-risk myelodysplastic syndromes

2021 ◽  
Author(s):  
Onyee Chan ◽  
Rami S Komrokji
Keyword(s):  
Clinical Trials ◽  
Myelodysplastic Syndromes ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Safety Data ◽  
Erythroid Differentiation ◽  
Fda Approval ◽  
The Us ◽  
Us Fda ◽  
Terminal Erythroid Differentiation

Transforming growth factor beta (TGF-β) signaling pathway is key to hematopoiesis regulation. Increased activation of this pathway contributes to ineffective terminal erythroid differentiation in myelodysplastic syndromes (MDS). Luspatercept is a novel fusion protein that traps TGF-β ligands preventing them from binding to Type II TGF-β receptors, thereby decreasing phosphorylated SMAD2/3 resulting in the downstream effect of promoting erythropoiesis. Seminal clinical trials using luspatercept, PACE-MD and MEDALIST, demonstrated impressive efficacy in the treatment of transfusion-dependent anemia in intermediate risk or lower MDS had led to the US FDA approval for this indication. This review summarizes luspatercept mechanisms of action, efficacy/safety data supporting its use and ongoing clinical trials in MDS.

scholarly journals How Will Aducanumab Approval Impact AD Research?

2021 ◽  
pp. 1-2
Author(s):  
M.W. Weiner ◽  
P.S. Aisen ◽  
L.A. Beckett ◽  
R.C. Green ◽  
W. Jagust ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Therapeutic Agent ◽  
Longitudinal Observational Study ◽  
Fda Approval ◽  
The Us ◽  
Accelerated Approval ◽  
Us Fda ◽  
First Time

The accelerated approval of aducanumab (AduhelmTM) by the US FDA is a momentous event. For the first time, a therapeutic agent that targets the neurobiology of Alzheimer’s disease (AD) is available for clinical use (1, 2). In addition to the FDA approval of aducanumab, the FDA has also provided “Breakthrough therapy designation” for Lilly’s Donanemab and Eisai’s Lecnemab which also are monoclonal antibodies that remove brain amyloid plaques and may slow cognitive decline. Aducanumab approval will impact clinical practice. The effects on AD clinical research will be profound in both positive and negative ways. This Editorial reflects the opinion of the leadership of the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a large multisite longitudinal observational study with the goal of validating biomarkers for clinical trials. ADNI data have been used to help design and statistically power many AD clinical trials, including the aducanumab studies.

Enrollment disparities in cancer clinical trials leading to FDA approvals between 2008 and 2020.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18501-e18501
Author(s):  
Ryan Huu-Tuan Nguyen ◽  
Yomaira Silva ◽  
Vijayakrishna K. Gadi
Keyword(s):  
Prostate Cancer ◽  
United States ◽  
Clinical Trials ◽  
Drug Approval ◽  
The United States ◽  
Cancer Clinical Trials ◽  
Cancer Prevalence ◽  
Fda Approval ◽  
The Us ◽  
Enrollment Data

e18501 Background: Cancer clinical trials based in the United States (US) have lacked adequate representation of racial and ethnic minorities, the elderly, and women. Pivotal clinical trials leading to United States Food and Drug Administration (FDA) approval are often multi-national trials and may also lack generalizability to underrepresented populations in the United States. We determined the racial, ethnic, age, and sex enrollment in pivotal trials relative to the US cancer population. Methods: We reviewed the FDA’s Drug Approvals and Databases for novel and new use drug approvals for breast, colorectal, lung, and prostate cancer indications from 2008 through 2020. Drugs@FDA was searched for drug approval summaries and FDA labels to identify clinical trials used to justify clinical efficacy that led to FDA approval. For eligible trials, enrollment data were obtained from FDA approval summaries, FDA labels, ClinicalTrials.gov, and corresponding journal manuscripts. Enrollment Fraction (EF) was calculated as enrollment in identified clinical trials divided by 2017 SEER cancer prevalence. All data sources were publicly available. Results: From 2008 through 2020, 60 drugs received novel or new use drug approval for breast, colorectal, lung, or prostate cancer indications based on 66 clinical trials with a total enrollment of 36,830. North America accounted for 9,259 (31%) enrollees of the 73% of trials reporting location of enrollment. Racial demographics were reported in 78% of manuscripts, 66% of ClinicalTrials.gov pages, and 98% of FDA labels or approval summaries. Compared with a 0.4% enrollment fraction among White patients, lower enrollment fractions were noted in Hispanic (0.2%, odds ratio [OR] vs White, 0.46; 95% confidence interval [CI], 0.43 to 0.49, P< 0.001) and Black (0.1%, OR 0.29; 95% CI 0.28 to 0.31, P< 0.001) patients. Elderly patients (age ≥ 65 years) were less likely than younger patients to be enrollees (EF 0.3% vs 0.9%, OR 0.27; 95% CI 0.26 to 0.27, P< 0.001) despite accounting for 61.3% of cancer prevalence. For colorectal and lung cancer trials, females were less likely than males (EF 0.7% vs 1.1%, OR 0.66; 95% CI 0.63 to 0.68, P< 0.001) to be enrolled. Conclusions: Black, Hispanic, elderly, and female patients were less likely to enroll in cancer clinical trials leading to FDA approvals from 2008 to 2020. Race and geographic enrollment data were inconsistently reported in journal manuscripts and ClinicalTrials.gov. The lack of appropriate representation of specific patient populations in these key clinical trials limits their generalizability. Future efforts must be made to ensure equitable access, representation, and reporting of enrollees that adequately represent the US population of patients with cancer.

Lasers for Onychomycosis

2016 ◽  
Vol 21 (2) ◽  
pp. 114-116 ◽  
Author(s):  
Aditya K. Gupta ◽  
Kelly A. Foley ◽  
Sarah G. Versteeg
Keyword(s):  
Laser Treatment ◽  
Clinical Trial Design ◽  
Temporary Increase ◽  
Drug Trials ◽  
Mycological Cure ◽  
Treatment Regimens ◽  
Fda Approval ◽  
The Us ◽  
Current Article ◽  
Us Fda

Many studies that have been recently published investigate the efficacy of laser treatment for onychomycosis. These studies support the current US Food and Drug Administration (FDA) approval of lasers for the ‘temporary increase in clear nail’. Clear nail growth is an important treatment goal for patients; however, many do not realise that laser treatment is not a cure for onychomycosis. The current article briefly reviews why lasers may be theoretically effective in treating onychomycosis and critically reviews published laser studies for onychomycosis in light of the standards employed in drug trials. Treatment regimens, efficacy endpoints, and the unit of analysis (nails vs patients) vary widely among published laser studies. Complete cure, mycological cure, and clinical improvement rates in laser studies are not reported or use such disparate criteria that comparison among studies is not possible. The US FDA has recently published guidelines for the use of medical devices in clinical trial design for onychomycosis. Future laser studies should adopt the FDA’s guidelines to allow for more consistency within the field and focus on the efficacy of lasers as monotherapy for onychomycosis.

scholarly journals Adverse Events in Elderly Hodgkin Lymphoma Patients Treated with Pembrolizumab or Nivolumab in the Real World

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3490-3490 ◽  
Author(s):  
Marjorie E Zettler ◽  
Chadi Nabhan ◽  
Ajeet Gajra ◽  
Bruce Feinberg
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Elderly Patients ◽  
Real World ◽  
Adverse Reactions ◽  
Age Group ◽  
Younger Patients ◽  
Fda Approval ◽  
The Us ◽  
Post Marketing

Introduction: Registry data indicate that 20% or more of Hodgkin lymphoma (HL) patients are ≥60; these HL patients have been labeled as elderly as their treatment has been associated with more toxicity, a higher relapse rate, and greater mortality relative to younger patients. The characteristics of HL in elderly patients differ from those in younger patients and may represent a biologically more aggressive disease. Further, elderly patients generally have a greater comorbidity burden than their younger counterparts, which may contribute to their under-representation in clinical trials. Nivolumab (NIVO) and pembrolizumab (PEMBRO) are both approved for treating relapsed/refractory HL based on studies that largely enrolled younger patients, as only about 10% of enrolled patients in the pivotal trials that led to their United States (US) Food and Drug Administration (FDA) approval were ≥60 years of age. Whether adverse events (AEs) related to these immunotherapies differ between younger and older HL patients is unknown and may have important clinical and practice implications. Therefore, we reviewed all post-marketing case reports from the FDA Adverse Events Reporting System (FAERS) Database involving NIVO or PEMBRO for HL and compared AEs and outcomes by age. Methods: The FAERS database is a repository of anonymized reports for product-related AEs, classified using the Medical Dictionary for Regulatory Activities (MedDRA) and categorized as serious or non-serious. The database was queried for cases involving NIVO or PEMBRO (and their respective trade names) from the FDA approval date for the HL indication (May 17, 2016 for NIVO; March 14, 2017 for PEMBRO) through March 31, 2019. Cases were excluded if the age of the patient was unknown, or if the case was reported outside the US. Comparisons of rates of AEs by age group were made using Fisher's exact test; statistical significance was determined at a two-sided α=0.05. Results: A total of 126 cases were retrieved (117 involving NIVO, 9 involving PEMBRO). One hundred and fourteen of the 126 cases (90%) were categorized as serious. Median age of all patients involved was 56 (range 10-89); 53 of the cases (42%) involved patients age 60 or older (Table). Overall, 8 cases had an outcome categorized as life-threatening; 20 cases resulted in death; 2 resulted in disability; and 74 resulted in hospitalization. A higher proportion of cases involving younger patients were categorized under the reaction group "neoplasms benign, malignant and unspecified" (16% vs. 2%; p&lt;0.01), and older patients had a greater incidence of infectious complications compared with their younger counterparts, though this was marginally significant (40% vs. 23%; p=0.05). The proportion of cases resulting in hospitalization was significantly higher in the ≥60 age group as compared to the &lt;60 age group (79% vs. 44%; p &lt;0.01). Adverse reactions that were common in clinical trials, such as fatigue, pyrexia, headache, peripheral neuropathy, upper respiratory tract infection, hypothyroidism, diarrhea, nausea and vomiting, did not show any significant associations by age group (all p values &gt;0.05). Conclusions: Although elderly patients comprise 20% of the HL patient population in the US, our post-marketing analysis indicates that AEs in this subgroup account for more than 40% of the total. This suggests that elderly HL patients experience a disproportional number of AEs compared to younger HL patients. While the types of AEs reported in post-marketing cases generally paralleled those observed in clinical trials of HL patients receiving NIVO or PEMBRO, hospitalizations and infections were more common in the elderly group. These differences in the adverse reactions and safety outcomes associated with PD-1 blockade therapy in HL patients may help inform clinical care and monitoring for AEs. Despite the inherent limitations of this study, our findings complement clinical trial safety data and provide insight into real-world trends in reported safety signals that merit further study. Disclosures Zettler: Cardinal Health: Employment. Nabhan:Aptitude Health: Employment. Gajra:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.

scholarly journals Pharmacotherapy for Patients with Obesity

2018 ◽  
Vol 64 (1) ◽  
pp. 118-129 ◽  
Author(s):  
Kishore M Gadde ◽  
John W Apolzan ◽  
Hans-Rudolf Berthoud
Keyword(s):  
Weight Loss ◽  
Clinical Trials ◽  
Weight Management ◽  
Neural Control ◽  
Safety Data ◽  
New Drugs ◽  
Future Research ◽  
The Us ◽  
Antiobesity Drugs

Abstract BACKGROUND Although pharmacotherapy is not the cornerstone of obesity treatment, it is a valuable tool that could be considered for patients who have not had adequate benefit from lifestyle interventions or who have difficulty maintaining initial weight loss over longer periods. CONTENT This review focuses on the role of antiobesity drugs, the mechanisms by which the drugs work, potential pharmacological targets in the neural control of food intake and regulation of body weight, the history of antiobesity drugs, a summary of efficacy and safety data from clinical trials, and the clinical application of pharmacotherapy. Currently, 5 approved drug therapies are available in the US for long-term weight management, with only 2 of these meeting the stronger Food and Drug Administration (FDA) criteria of 5% weight loss relative to a placebo after 1 year and others receiving approval based on the categorical criterion of the proportions of patients achieving 5% weight loss. Interpretation of the results of clinical trials conducted before regulatory agency approval is limited by high dropout rates; thus, the results might not be replicable in clinical practice settings. Many patients who are suitable candidates for pharmacotherapy are not using the new drugs due to lack of insurance coverage and high out-of-pocket costs. SUMMARY With the availability of 4 new drugs since 2012, clinicians in the US now have more tools for long-term weight management. The quality of pharmacotherapy clinical investigations needs considerable improvement. Future research should focus on examining the mediators and moderators of response.

Axitinib: Common questions related to real-world use of a new treatment option in advanced renal cell carcinoma.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 538-538
Author(s):  
Diane Lorraine Borst ◽  
Lillian Shahied Arruda ◽  
Elizabeth A. MacLean ◽  
Yazdi K. Pithavala ◽  
James E. Morgado ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Medical Information ◽  
Medical Community ◽  
Prescription Data ◽  
Fda Approval ◽  
Clinical Scenarios ◽  
The Us ◽  
Stage Renal Disease ◽  
Dose Modifications

538 Background: Axitinib is a next generation VEGFR inhibitor approved in the US in Jan 2012 for advanced RCC after failure of one prior systemic therapy. Post approval questions may arise in the medical community regarding clinical scenarios which may not have been addressed in the clinical trials. We present the most common inquiries for axitinib submitted to Pfizer US Medical Information (MI) during the first 18 months post FDA approval and review available information that addresses these questions. Methods: MI inquiries were analyzed during the 6-mo period immediately post FDA approval and a second 6-mo period approximately 1 yr later. To gain insight into real-world dosing patterns, de-identified prescription data from Feb 2012-July 2013 obtained from the 21 specialty pharmacies (SP) in the US that distribute axitinib (Inlyta) were analyzed. Algorithms were developed to define dose modifications using dosage strengths dispensed and time between prescription fills over 2 day and 14 day windows. Results: The most frequent inquiries (>5%) common to both time periods included use in patients (pts) who were unable to swallow medication, use in patients with renal impairment (RI), and general dosage and administration questions. A method for preparation of an axitinib oral suspension for NG tube administration was developed for use in pts unable to swallow axitinib tablets. No dose adjustments are recommended for pts with RI; however axitinib should be used with caution in pts with end stage renal disease. The most common dose dispensed, using a 2 day window, was 5 mg bid, comprising 9659 (70%) of all dispensed prescriptions, with 789 (6%) at the 10 mg bid dose. An assessment of the most recent 7 months in the evaluation period shows that 16% and 19% of prescriptions were for doses >5 mg bid or <5 mg bid, respectively. Similar findings were observed using a 14 day window. Conclusions: Axitinib questions in the medical community revolve primarily around use in specific populations and dosing. Analysis of SP data revealed that dose modifications occurred at a lower frequency than observed in clinical trials. Further analysis is needed to understand outcomes associated with the dose modifications made in these patients.

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