Desirable Characteristics of Hepatitis C Treatment Regimens: A Review of What We Have and What We Need.

There have been dramatic advancements in the treatment of chronic hepatitis C (HCV) infection. This is largely due to the approval of several direct-acting antiviral agents (DAAs) from a variety of medication classes with novel mechanisms of action. These therapies are a welcomed advancement given their improved efficacy and tolerability compared to pegylated interferon and ribavirin (RBV)-based regimens. These convenient, all-oral regimens treat a variety of genotypes and often offer high cure rates in a variety of HCV-infected populations. While there are several benefits associated with these therapies, there are also notable shortcomings. Shortcomings include diminished response or need for adjunctive RBV in difficult-to-treat populations (decompensated cirrhosis, active substance abuse patients, advanced kidney disease, etc.), activity against select genotypes, substantial drug-drug interaction potential, and high cost. Therefore, while current DAA-based therapies have several favorable attributes, each also has its limitations. The purpose of this review is to (1) identify the characteristics of an ideal HCV treatment regimen, (2) describe desirable features of existing regimens, (3) summarize limitations of existing regimens, and (4) introduce promising emerging therapies. This manuscript will serve as a guide for evaluating the caliber of future HCV treatment regimens

Liver transplantation for viral hepatitis in 2015

Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release

A multicenter, open-label, long-term safety and tolerability study of DFN-02, an intranasal spray of sumatriptan 10 mg plus permeation enhancer DDM, for the acute treatment of episodic migraine.

BackgroundDFN-02 is a novel intranasal spray formulation composed of sumatriptan 10 mg and a permeation-enhancing excipient comprised of 0.2% 1-O-n-Dodecyl-β-D-Maltopyranoside (DDM). This composition of DFN-02 allows sumatriptan to be rapidly absorbed into the systemic circulation and exhibit pharmacokinetics comparable to subcutaneously administered sumatriptan. Rapid rate of absorption is suggested to be important for optimal efficacy. The objective of this study was to evaluate the safety and tolerability of DFN-02 (10 mg) in the acute treatment of episodic migraine with and without aura over a 6-month period based on the incidence of treatment-emergent adverse events and the evaluation of results of clinical laboratory tests, vital signs, physical examination, and electrocardiograms.MethodsThis was a multi-center, open-label, repeat-dose safety study in adults with episodic migraine with and without aura. Subjects diagnosed with migraine with or without aura according to the criteria set forth in the International Classification of Headache Disorders, 2nd edition, who experienced 2 to 6 attacks per month with fewer than 15 headache days per month and at least 48 headache-free hours between attacks, used DFN-02 to treat their migraine attacks acutely over the course of 6 months.ResultsA total of 173 subjects was enrolled, 167 (96.5%) subjects used at least 1 dose of study medication and were evaluable for safety, and 134 (77.5%) subjects completed the 6-month study. A total of 2211 migraine attacks was reported, and 3292 doses of DFN-02 were administered; mean per subject monthly use of DFN-02 was 3.6 doses. Adverse events were those expected for triptans, as well as for nasally administered compounds. No new safety signals emerged. Dysgeusia and application site pain were the most commonly reported treatment-emergent adverse events over 6 months (21% and 30.5%, respectively). Most of the treatment-emergent adverse events were mild. There were 5 serious adverse events, all considered unrelated to the study medication; the early discontinuation rate was 22.5% over the 6-month treatment period.ConclusionDFN-02 was shown to be well tolerated when used over 6 months to treat episodic migraine acutely

Health Care Costs and the Arc of Innovation

Health care costs continue their inexorable rise, threatening America’s long-term fiscal stability, competitiveness, and standard of living. Over the past half-century, efforts to rein in spending have uniformly failed. In this Article, we explain why, breaking with standard accounts of regulatory and market dysfunction. We point instead to the nexus of economics, mutual empathy, and social expectations that drives medical innovation and locks in low-value technologies. We show how law reflects and reinforces this nexus and how and why health-policy-makers avert their gaze. Next, we propose to circumvent these barriers instead of surmounting them. Rather than targeting today’s excessive spending, we seek to leverage available legal tools to bend the arc of innovation, away from marginally-beneficial technology and toward high-value advances. To this end, we set forth a novel, value-based approach to pricing and patent protection—one that departs sharply from current practice by rewarding innovators in proportion to the therapeutic benefits new tests and treatments yield. Using cancer therapy as an example, we explain how emerging information technology and large troves of electronic clinical data are opening the way to near-real-time assessment of efficacy. We then show how such assessment can power ongoing adjustment of pricing and patent terms. Finally, we offer a blueprint for how laws governing health care payment and intellectual property can be tailored to realize this value-focused vision. For the reasons we lay out, the transformation of incentives we urge will both slow clinical spending growth and greatly enhance the social value that this spending yields

Are new models needed to optimize the utilization of new medicines to sustain healthcare systems?

Medicines have made an appreciable contribution to improving health. However, even high-income countries are struggling to fund new premium-priced medicines. This will grow necessitating the development of new models to optimize their use. The objective is to review case histories among health authorities to improve the utilization and expenditure on new medicines. Subsequently, use these to develop exemplar models and outline their implications. A number of issues and challenges were identified from the case histories. These included the low number of new medicines seen as innovative alongside increasing requested prices for their reimbursement, especially for oncology, orphan diseases, diabetes and HCV. Proposed models center on the three pillars of pre-, peri- and post-launch including critical drug evaluation, as well as multi-criteria models for valuing medicines for orphan diseases alongside potentially capping pharmaceutical expenditure. In conclusion, the proposed models involving all key stakeholder groups are critical for the sustainability of healthcare systems or enhancing universal access. The models should help stimulate debate as well as restore trust between key stakeholder groups

2016 Pipeline Report HIV and TB

HIV and TB: Drugs, Diagnostics, Vaccines, Preventive Technologies, Research Toward a Cure, and Immune-Based and Gene Therapies in Developmen

WAO guideline for the management of hereditary angioedema

Hereditary Angioedema (HAE) is a rare disease and for this reason proper diagnosis and appropriate therapy are often unknown or not available for physicians and other health care providers. For this reason we convened a group of specialists that focus upon HAE from around the world to develop not only a consensus on diagnosis and management of HAE, but to also provide evidence based grades, strength of evidence and classification for the consensus. Since both consensus and evidence grading were adhered to the document meets criteria as a guideline. The outcome of the guideline is to improve diagnosis and management of patients with HAE throughout the world and to help initiate uniform care and availability of therapies to all with the diagnosis no matter where the residence of the individual with HAE exists