Thanks to all of our readers for a great 2016. Below is a top 10 countdown of Advera Health's most downloaded reports of the year with links to access the free downloads.
Zepatier (elbasvir, grazoprevir), the latest treatment for chronic hepatitis C, with mostly mild to moderate adverse reactions listed on its label, appears to have a less risky safety profile than Sovaldi (sofosbuvir) and a similar safety profile as Harvoni (sofosbuvir and ledipasvir). As a standalone therapy, Harvoni appears more effective in Treatment Naïve pa tients and both Zepatier and Harvoni seem to have similar efficacy in Treatment Experienced patients through various clinical trials. Both Harvoni and Sovaldi have AEs like cardiac arrest, suicidal ideation, and suicide listed on their label, which are not on Zepatier’s label, and our RxSignal analytic has identified potential future FDA label changes for the following serious AEs for Sovaldi: progressive multifocal leukoencephalopathy, Stevens Johnson syndrome, toxic epidermal necrolysis and drug induced liver injury. Download Full Report
An evidence aggregation platform is a web based software-as-a-service (SaaS) application that takes multiple, disparate sources of data, or evidence, and combines those data together using analytics to create new insight.
Throughout this White Paper specific use cases will demonstrate why evidence aggregation platforms are becoming a vital source of intelligence for various healthcare decision makers in both pharmaceutical companies and managed care organizations. Download Full Report
Biogen’s reformulated version of daclizumab, Zinbryta (daclizumab high yield process), is a once monthly subcutaneous injection monoclonal antibody multiple sclerosis (MS) treatment. Zinbryta showed superior efficacy to Avonex (interferon beta 1a) in reducing Annual Relapse Rates and Mean Number of Gadolinium (GD) Enhancing Lesions in the DECIDE study and showed similar improved efficacy versus placebo in the SELECT study. Serious adverse event (AE) Rates were slightly higher for Zinbryta vs. Avonex (24% vs. 21%) in the DECIDE study and were roughly 20.7% across all Zinbryta studies in Advera’s Evidex plat form. According to Evidex, the main serious adverse event concerns across all trials for Zinbryta are 1) Skin and Subcutaneous Disorders (incl. Hypersensitivity) (2.08% in Zinbryta-treated vs. 0.18% in control groups), 2) Infections and Infestations (4.15% vs. 1.78%), 3) Autoimmune conditions (0.88% vs. 0.00%),and 4) Blood and Lymphatic Disorders (0.57% vs. 0.18%). Compared to other monoclonal antibody treatments for MS, Zinbryta has less autoimmune risk than Lemtrada (alemtuzumab) and less serious infection risk than both Tysabri (natalizumab) and Lemtrada, but has more skin/hypersensitivity risk than both treatments. Download Full Report
Merck’s new oral, once weekly Dipeptidyl Peptidase 4 (DPP4) inhibitor omarigliptin, approved in Japan as Marizev, is awaiting FDA approval in US. In head-to-head trials, Marizev (omarigliptin) showed statistically non-inferior efficacy in reducing glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels when compared to Januvia (sitagliptin) both in a monotherapy trial as well as in a combination trial with metformin. In their respective head-to-head trials with sulfonylureas, Marizev (omarigliptin) was less impressive in its relative reduction of A1C and FPG compared to Januvia. Marizev (omarigliptin) presented a higher rate of serious adverse events than Januvia in the two head-to-head trials, showing elevated rates of hepatobiliary events, cardiovascular issues, and prostate cancer. Download Full Report
Gilead’s pan-genomic investigational Hepatitis C drug Epclusa (sofosbuvir/velpatasvir) seems to have a similar safety profile compared to Sovaldi (sofosbuvir), Harvoni (sofosbuvir/ ledipasvir), Daklinza (daclatasvir), and Viekira Pak (ombitasvir/paritaprevir/ritonavir). Through the clinical trials, this drug: 1) showed impressive efficacy in terms of Sustained Viral Repose after 12 weeks (SVR12) in Hepatitis C Virus (HCV) genotypes 1-6; 2) was effective even in patients with advanced cirrhosis and failed prior treatments; and 3) had mostly mild adverse events (AEs) and low serious AE (e.g. sepsis, gastrointestinal bleeding, infections, hepatic encephalopathy and hepatic cancer) rates relative to its comparators. Though our analysis of the clinical trial data support the possibility of this drug to be a safe genome-wide anti-HCV drug, close post-marketing surveillance after its approval will help us to identify further safety issues. Download Full Report
Based on analysis of clinical trial evidence on Advera’s Evidex platform, Sanofi’s Adlyxin (lixisenatide) showed a slightly safer profile compared to Victoza (liraglutide) based on a lower serious AE rate in head-to-head trials, and no associated thyroid cancer risk which has been tied to Victoza in rare cases. Adlyxin (lixisenatide) improved glycemic control both as monotherapy and as an add-on therapy to oral anti-diabetic drugs and insulin and showed a safe cardiovascular profile in patients in a cardiovascular safety trial,but showed inferior efficacy in reducing Hb1Ac and FPG in head-to-head trials vs. Victoza (liraglutide) and Byetta (exenatide). Considering the label warning against anaphylactic reactions associated with usage of Adlyxin (lixisenatide), close post-marketing surveillance will reveal the extent of this and other safety issues for this drug. Download Full Report
Roche/Genentech’s ocrelizumab (Ocrevus) received breakthrough designation from FDA on February 2016, for showing promising results in treating the hitherto untreatable form of MS, primary progressive MS (PPMS). Through the clinical trials for Relapsing Multiple Sclerosis (RMS) and PPMS, the drug showed significant efficacy improvements and a similar safety profile compared to its comparator interferon-beta 1a (Rebif). Our analysis of the early Phase III clinical trial data aggregated in Evidex revealed a slight imbalance in the incidence of malignancies (4 cases vs. 2 cases for Rebif) and a small number of potentially drug-induced fatalities. Serious infections like progressive multifocal leukoencephalopathy (PML) were not observed in the clinical trials, but warrant a close scrutiny, especially since this drug’s non-MS clinical trials were suspended due to an increased risk of serious opportunistic infections that were sometimes fatal. Download Full Report
Tresiba (insulin degludec), the FDA-approved long-acting injectable insulin analog, seems to have a similar safety profile to its comparator Lantus (insulin glargine), based on their matching labeled serious adverse events (AEs). In head-to-head clinical trials comparing these two insulin analogs, Tresiba (insulin degludec) was statistically non-inferior to Lantus (insulin glargine) in reducing glycosylated hemoglobin levels, fasting glucose levels & confirmed hypoglycemic episodes, but the rate of nocturnal hypoglycemic events were significantly reduced especially in type 2 diabetes patients treated with Tresib a (insulin degludec). Both the drugs had similar rates of serious AEs through the clinical trials. Based on real-world adverse events reported for Lantus (insulin glargine), our analytics have identified: non-labeled Active RxSignals for serious events such as liver transplant, cerebral thrombosis, and myelitis transverse; an RxScore of 43.88; and an RxCost per prescription of $1.62. Download Full Report
Nucala (mepolizumab), recently approved by FDA for use with other medicines to treat severe refractory asthma of eosinophilic subtype, seems to have a less risky safety profile than its comparator, Xolair (omalizumab), as only 2/50 of Nucala’s (mepolizumab) labeled adverse events (AEs) are Important Medical Event (IME) serious terms (angioedema and lower respiratory tract infection). Through the clinical trials were done under varying designs, Nucala appeared to be similarly effective as Xolair in reducing asthma exacerbations and reducing corticosteroid usage, but is approved to treat a much narrower indication than Xolair. For the following reasons, Advera Health Analytics has concluded that Xolair (omalizumab) may have a riskier safety profile than Nucala (mepolizumab): 18/87 AEs listed on Xolair’s (omalizumab) label are IME serious terms, including anaphylactic reactions, cardiovascular AEs, and malignancies; our analytics identified unlabeled “Active” safety signals for serious AEs like Amyotrophic Lateral Sclerosis (ALS), Toxic Epidermal Necrosis (TEN) and aortic stenosis; Xolair (omalizumab) has a relatively high RxScore of 70.79, and an additional RxCost burden of $31.64 per prescription based on serious AEs reported post-market. Download Full Report
PB272 (neratinib), currently under review by FDA, will likely be approved for the extended adjuvant treatment of HER2-positive early stage breast cancer. Aggregated serious adverse event rates were higher across all neratinib trials in the Evidex database compared to control groups (12.51% vs. 7.22%, respectively), and the highest incidence safety issues were gastrointestinal disorders including serious diarrhea (30.16% vs. 2.22% control). Download Full Report