Virginia Noxon

Regulatory and clinical considerations for biosimilar oncology drugs

Biological oncology products are integral to cancer treatment, but their high costs pose challenges to patients, families, providers, and insurers. The introduction of biosimilar agents-molecules that are similar in structure, function, activity, immunogenicity, and safety to the original biological drugs-provide opportunities both to improve health-care access and outcomes, and to reduce costs. Several international regulatory pathways have been developed to expedite entry of biosimilars into global marketplaces. The first wave of oncology biosimilar use was in Europe and India in 2007. Oncology biosimilars are now widely marketed in several countries in Europe, and in Australia, Japan, China, Russia, India, and South Korea. Their use is emerging worldwide, with the notable exception of the USA, where several regulatory and cost barriers to biosimilar approval exist. In this Review, we discuss oncology biosimilars and summarise their regulatory frameworks, clinical experiences, and safety concerns.

Epoetin zeta in the management of anemia associated with chronic kidney disease, differential pharmacology and clinical utility.

Epoetin zeta was granted marketing authorization in October 2007 by the European Medicines Agency as a recombinant human erythropoietin erythropoiesis-stimulating agent to treat symptomatic anemia of renal origin in adult and pediatric patients on hemodialysis and adults on peritoneal dialysis, as well as for symptomatic renal anemia in adult patients with renal insufficiency not yet on dialysis. Currently, epoetin zeta can be administered either subcutaneously or intravenously to correct for hemoglobin concentrations ≤10 g/dL (6.2 mmol/L) or with dose adjustment to maintain hemoglobin levels at desired levels not in excess of 12 g/dL (7.5 mmol/L). This review article focuses on epoetin zeta indications in chronic kidney disease, its use in managing anemia of renal origin, and discusses its pharmacology and clinical utility.

Systematic Approach to Pharmacovigilance beyond the Limits: The SouthernNetwork on Adverse Reactions (SONAR) Projects

As of 2013, the Southern Network on Adverse Reactions (SONAR) team described 50 significant adverse drug reactions (sADRs) associated with FDA approved drugs. The team also investigates policy issues surrounding pharmacovigilance. Herein we describe the systematic approach to pharmacovigilance taken by the Southern Network on Adverse Reactions and discuss major findings from the group. By 2015, the team hopes to have identified 20 additional sADRs focusing on biologics, biosimilars, and biobetters. The ultimate goal of SONAR is to decrease the timescale between ADR detection and the dissemination of information regarding the sADR

Patterns of use and expenses associated with mail-service pharmacy in adults with diabetes

OBJECTIVES To identify socioeconomic factors associated with mail-service pharmacy use and compare the differences in disease-specific prescription medication and medical utilization expenses in a nationally representative sample of adults with diabetes. DESIGN A retrospective, longitudinal, cross-sectional study. SETTING United States in 2006-11. PARTICIPANTS Medical Expenditure Panel Survey household component (MEPS-HC) participants aged 18 years or older diagnosed with diabetes and prescribed antidiabetic medications. MAIN OUTCOME MEASURES Likelihood of mail-service pharmacy use, diabetes-related medical utilization, and medication expenses. RESULTS Among 4,430 eligible participants identified in the 2006-11 surveys, representing more than 83 million U.S. individuals, nearly 13% of the participants obtained two-thirds or more of their antidiabetic medications via mail service predominantly. Mail-service pharmacy users were older, had high school or college degrees, had higher incomes, and were more likely to be covered by private insurance. There were no significant differences in diabetes-related medical utilization and drug expenses between the two groups. CONCLUSION Besides pharmacy benefit design, sociodemographic and economic factors influenced drug dispensing channel use (mail service versus community pharmacy). No significant differences in diabetes-related drug and medical expenses between mail-service and community pharmacy users were observed.

Melanoma complicating treatment with natalizumab for multiple sclerosis: A report from the Southern Network on Adverse Reactions (SONAR)

A 43‐year‐old female with multiple sclerosis developed urethral melanoma. The only potential risk factor was treatment with natalizumab, a humanized monoclonal antibody against α4 integrins. To investigate the risk‐exposure relationship, we reviewed this case, all other published cases, and cases of natalizumab‐associated melanoma reported to regulatory agencies. Data sources included the Food and Drug Administrations (FDA) Adverse Event Reporting System (FAERS) (2004–2014), a FDA Advisory Committee Meeting Report, and peer‐reviewed publications. In the United States, the manufacturer maintains an FDA‐mandated Tysabri Safety Surveillance Program (part of the Tysabri Outcomes Unified Commitment to Health (TOUCH)) of natalizumab‐treated patients. We statistically compared reporting completeness for natalizumab‐associated melanoma cases in FAERs for which information was obtained entirely from the TOUCH program versus cases where FAERS information was supplemented by TOUCH program information. FAERS included 137 natalizumab‐associated melanoma reports in patients with multiple sclerosis. Median age at melanoma diagnosis was 45 years (range: 21–74 years). Changes in preexisting nevi occurred in 16%, history of cutaneous nevi occurred in 22%, diagnosis within 2 years of beginning natalizumab occurred in 34%, and 74% had primary surgical treatment. Among seven natalizumab‐treated MS patients who developed biopsy‐confirmed melanoma on treatment and reported in the literature, median age at diagnosis was 41 years (range: 38–48 years); and the melanoma diagnosis occurred following a median of 12 natalizumab doses (range: 1–77 doses). A history of mole or nevi was noted in four patients and a history of prior melanoma was noted in one patient. Completeness scores for reports were significantly lower for FAERS cases reported from the TOUCH program versus FAERS cases supplemented by TOUCH information (median score of 2 vs. 4 items out of 8‐possible items, P < 0.0007). Clinicians should monitor existing nevi and maintain suspicion for melanoma developing in natalizumab‐treated patients. The TOUCH Safety Surveillance Program, currently focused on progressive multifocal leukoencephalopathy, should be expanded to include information on other serious complications including malignancies, particularly if they are immunologic in nature.

Venue of receiving diabetes self-management education and training and its impact on oral diabetic medication adherence

AIMS To determine predictors associated with the diabetes self-management education and training (DSME) venue and its impact on oral antidiabetic (OAD) medication adherence. METHODS The Medical Expenditure Panel Survey household component (MEPS-HC) data (2010-2012) identified adults with diabetes prescribed OAD medication(s) who completed a supplemental Diabetes Care Survey (DCS). Based on the DCS responses to questions about the number and type of DSME venue(s), two groups were created: (1) multiple venues (a physician or health professional plus internet and/or group classes) vs (2) single venue (physician or health professional only). The medication possession ratio (MPR) measured medication adherence, with 0.80 the cut-point defining adherent. Logistic regression examined factors associated with the DSME venue and its effect on OAD medication adherence. RESULTS Of the 2119 respondents, 41.6% received DSME from multiple venues. Age (<65years), education-level (college or higher), high-income, and diet modification were significantly more likely associated with receiving DSME from multiple venues. In single vs multiple venues, medication adherence was suboptimal (mean MPR 0.66 vs 0.64, p=0.245), and venue showed no influence on adherence (OR: 0.92, 95% CI, 0.73-1.16). CONCLUSION Sociodemographic characteristics influence where adults with diabetes receive DSME. Adding different DSME venues may not address suboptimal OAD medication adherence.

Tale of Two Erythropoiesis-Stimulating Agents: Utilization, Dosing, Litigation, and Costs of Darbepoetin and Epoetin Among South Carolina Medicaid-Covered Patients With Cancer and Chemotherapy-Induced Anemia

PURPOSE The US Food and Drug Administration (FDA) has approved epoetin and darbepoetin for chemotherapy-induced anemia (CIA). Approved epoetin and darbepoetin dosing schedules were three times per week and weekly, respectively, although off-label, less frequent scheduling was common. In 2004, 2007, and 2008, a US Food and Drug Administration Advisory Committees warned of risks associated with erythropoiesis-stimulating agents. During this period, lawsuits alleging illegal darbepoetin marketing practices have concluded, resulting in

Natalizumab-associated melanoma: A report of 139 cases from the southern network on adverse reactions (SONAR)

1.1 billion in fines and settlements and one criminal conviction. No prior study, to our knowledge, has reported on the use of darbepoetin versus epoetin for CIA. METHODS We evaluated the dosing, utilization, and costs of erythropoiesis-stimulating agents among 3,761 South Carolina Medicaid patients with CIA. RESULTS Epoetin and darbepoetin utilization rates were 22% and 28% in 2003, 10% and 33% in 2007, and 3% and 7% in 2010, respectively. Mean per-patient per-administration epoetin and darbepoetin doses were 40,983 IU and 191 µg, respectively, in 2003 and 47,753 IU and 369 µg, respectively, in 2010. Mean monthly patient costs for epoetin and darbepoetin were

The “Double Whammy”: Effects of erythropoiesis stimulating agents (ESAs) when administered to patients with both end stage renal disease (ESRD) and cancer.

1,030 and

The Effect of Depression on Adherence To Hormone Therapy in Breast Cancer Patients

981, respectively, in 2003 and