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Hepatitis C-TMC435 ;MedivirAB Completed Enrollment of Three Global Phase 3 Trials
Video; Victrelis, and Incivek-2 new drugs to fight Hepatitis C
Hepatitis C; Response To Treatment Geno 3-fibrosis but not race encourages relapse
FDA Request That H&P Recall Povidone Iodine Prep Solutions W-other Multiple brands affected
Update;
Beleaguered wipe-maker hires new COO; prepares to reopen
H&P Industries hires former Abbott Laboratories executive to rebuild firm
A Wisconsin firm shut down after making and distributing contaminated alcohol wipes and other medical products blamed for infections and deaths has hired a new chief operating officer as officials work to reopen the company.
Todays News
Telaprevir Markedly Improves HCV Genotype 1 Cure Rates
From Journal Watch ; Journal Watch Gastroenterology
Atif Zaman, MD, MPH
Authors and Disclosures
Posted: 08/31/2011; Journal Watch © 2011 Massachusetts Medical Society
Abstract and Introduction
Abstract
Final results of phase III trials show that telaprevir plus standard therapy with peginterferon alfa-2a and ribavirin was more effective than standard therapy alone.
Introduction
Recently, telaprevir-based triple therapy (i.e., in combination with peginterferon alfa-2a and ribavirin) was approved for the treatment of chronic hepatitis C virus (HCV) infection. The final results of the international phase III trials for both treatment-naive and treatment-experienced patients with HCV genotype 1 infection are now available.
In the first of two industry-sponsored, double-blind, placebo-controlled trials, 1095 treatment-naive patients were randomized to receive either triple therapy for 12 weeks followed by peginterferon plus ribavirin for 12 weeks — or 36 weeks if HCV RNA was detectable at weeks 4 or 12 — (T12PR group); triple therapy for 8 weeks followed by peginterferon plus ribavirin for either 16 or 36 weeks (T8PR group); or peginterferon plus ribavirin for 48 weeks (PR group).
In the second trial, 663 treatment-experienced patients were randomized 2:2:1 to receive either triple therapy for the first 12 weeks followed by 36 weeks of peginterferon plus ribavirin (T12PR48 group), a 4-week lead-in of peginterferon plus ribavirin followed by 12 weeks of triple therapy and then 32 weeks of peginterferon plus ribavirin (lead-in T12PR48 group), or peginterferon plus ribavirin for 48 weeks (PR48 group). In both trials, doses were 750 mg every 8 hours for telaprevir, 180 µg weekly for peginterferon alfa-2a, and 1000–1200 mg daily for ribavirin. The primary endpoint was sustained virologic response (SVR).
For treatment-naive patients, SVR rates were higher in the T12PR and T8PR groups than in the PR group — 75% and 69% versus 44%; P<0.001. Although the numbers of patients who were black or had advanced fibrosis were small in the study cohort (7% and 20%, respectively), in both subgroups, SVR rates were higher in the telaprevir groups than the peginterferon plus ribavirin group. Among treatment-experienced patients, SVR rates for arms T12PR48, lead-in T12PR48, and PR48, respectively, were 83%, 88%, and 24% for previous relapse; 59%, 54%, and 15% for previous partial response; and 29%, 33%, and 5% for previous null response (P<0.001 for all comparisons).
In general, virologic failure in the telaprevir groups was attributable primarily to the development of drug resistance. In both studies, the telaprevir groups had higher rates of anemia, rashes, pruritus, and gastrointestinal problems than the peginterferon plus ribavirin group. Discontinuation of medications for any reason ranged from 10% to 15% for the telaprevir regimens and from 7% to 10% for the peginterferon plus ribavirin regimen
Comment
These companion studies demonstrate that telaprevir-based regimens are significantly more effective in HCV genotype 1–infected patients than peginterferon plus ribavirin alone — for both treatment-naive and treatment-experienced patients. Although more adverse events occurred in the telaprevir-treated groups, discontinuation rates were still relatively low. Overall, the best SVRs were seen in treatment-naive and prior-relapse patients (≥75%), followed by previous partial responders, treatment-naive blacks, and patients with advanced fibrosis (50%–60%), and last, previous null responders (30%). Therefore, caution should be exercised in treating null responders, especially since the majority of virologic failure leads to drug resistance.
References
Sexual Transmission of HCV Among HIV-Infected MSM, 2005-2010
This new report discusses the rates of sexual transmission of HCV among gay men already infected with HIV. How prevalent is it?
Morbidity & Mortality Weekly Report, August 2011
Abstract and Introduction
Characteristics of Case-Patients
Case-Control Study
Results of Phylogenetic Analyses
Editorial Note
References
Sidebar
Poxvirus vaccine is safe and decreases viral load in patients with chronic Hepatitis C
Poxvirus vaccine is safe, induces T-Cell responses, and decreases viral load in patients with chronic Hepatitis C, reports the latest issue of Gastroenterology.
Therapy for chronic hepatitis C has limited efficacy, adverse effects, and high costs.
Cohort and vaccine-based preclinical studies have indicated the importance of T-cell–based immunity in controlling viral infection.
TG4040 is a recombinant poxvirus vaccine that expresses the hepatitis C virus (HCV) proteins NS3, NS4, and NS5B.
Dr François Habersetzer and colleagues from France performed a phase I clinical trial to assess the safety, immunogenicity, and early antiviral efficacy of TG4040 in patients with chronic hepatitis C.
In an open-label, dose-escalating study, patients with mild chronic hepatitis C (genotype 1) were assigned to 3 groups of 3 patients each.
All 3 doses of TG4040 were well tolerated
Gastroenterology
They received subcutaneous injections of 106, 107, or 108 plaque-forming units of TG4040 on study days 1, 8, and 15.
The team gave 6 additional patients the highest dose of vaccine.
Patients were followed for 6 months after the last injection.
T-cell–based and antibody responses and levels of HCV RNA were measured.
All 3 doses of TG4040 were well tolerated, without serious adverse events.
The researchers observed that vaccine-induced HCV-specific cellular immune responses in 33% of patients.
A transient decrease in circulating levels of HCV RNA was observed in 8 patients, in 5 patients, the lowest level of HCV RNA was observed on day 37, after the first injection.
The research team found that the most pronounced decrease in viral load occurred in 2 patients, who also had marked vaccine-induced T-cell responses.
Dr Habersetzer's team concludes, "In patients with chronic hepatitis C, the viral-vector–based vaccine TG4040 had a good safety profile, induced HCV-specific cellular immune responses, and reduced viral load."
"This vaccine should be investigated in further clinical studies, in combination with standard of care."
Gastroenterol 2011: 141(3): 890-89931 August 2011
Clinic may have exposed patients to HIV, hepatitis: How to stay safe
The former employee reportedly changed needles on these devices each time, but reused the rest of the devices - which may trap microscopic amounts of blood and cross-contaminate a patient, reported WMTV. Further, the insulin pen wasn't even supposed to be used on patients.
Spatial mapping of hepatitis C prevalence in recent injecting drug users in contact with services.
SUMMARY
In developed countries the majority of hepatitis C virus (HCV) infections occur in injecting drug users (IDUs) with prevalence in IDUs often high, but with wide geographical differences within countries. Estimates of local prevalence are needed for planning services for IDUs, but it is not practical to conduct HCV seroprevalence surveys in all areas. In this study survey data from IDUs attending specialist services were collected in 52/149 sites in England between 2006 and 2008. Spatially correlated...
Transplant
Changes To Distribution Of Livers For Transplant Proposed
Main Category: Liver Disease / Hepatitis
Also Included In: Transplants / Organ Donations
Article Date: 31 Aug 2011 - 1:00 PDT
Transplantation specialists have proposed changes to the allocation and distribution of organs used for liver transplants. The recommended policy modifications take into account the scarcity of available organs, ensuring rapid allocation and delivery of the organ to those most in need in order to reduce mortality for waitlisted patients. Details of the proposed model are available in the September issue of Liver Transplantation, a journal published by Wiley Blackwell on behalf of the American Association for the Study of Liver Diseases.
A number of diseases affect liver function, including hepatitis B and C, nonalcoholic fatty liver disease, and autoimmune liver disease. The severity of liver disease ranges from mild to more severe forms that are life-threatening. When the liver fails (end stage liver disease) and patient life is at risk for death, transplantation is the recommended option. However, the scarcity of donor organs is one of the greatest concerns for transplantation candidates and a challenge for clinicians who treat them. According to the Organ Procurement and Transplant Network (OPTN) there are more than 16,000 Americans on the waiting list to receive a liver as of August 2011.The current model in the U.S. defines allocation as the order of patients on a particular waiting list.
Since 2002, the transplantation community has used the Model for Endstage Liver Disease (MELD) score and length of time on waiting list to rank patients for allocation of the available liver. Distribution is the determination of the area to which a donor liver will be offered, and uses a local, regional, national system to distribute available livers for transplant.
The OPTN donation service area that is assigned to the organ procurement organization is the designated "local" region using this system.
In an examination of the allocation and distribution of livers for transplantation, the authors reviewed the system currently used to determine which patients receive organs for transplant and provided alternative models to promote a more equitable distribution. "Given the disparity between supply and demand of deceased donor livers, there will always be differences of opinion as to which patient should be transplanted first," said lead author Kenneth Washburn, M.D., with the University Transplant Center, a partnership of The University of Texas Health Science Center at San Antonio and one of its primary clinical partners, the University Health System. "Any system that redistributes organs from low-need to high-need areas will not please all stakeholders," he added.
The authors note that most deaths on the waiting list occur in patients with low MELD scores the largest patient group on the list and allocating organs to this group would not reduce the overall death rate due to the low and unpredictable individual mortality risk. Since the largest number of deaths on the waiting list cannot be prevented through organ allocation, the authors suggest a system should focus on patients with higher MELD scores who have the greatest risk of death.
Based on prior feedback from involved stakeholders, small incremental changes to the current system would be the best method for making allocation policy improvements. One potential next step, according to the authors, is moving from a "share 15" regional model to a "national 15" sharing model which would direct donated livers to waitlist patients with MELD score of 15 at the regional then national level before candidates at the local level whose MELD score is less than 15 would be offered a liver.
Another incremental change the authors propose is regional sharing for the sickest patients with high MELD scores (> 35). Redistribution of donated livers to this patient group results in a decrease in waitlist mortality for these patients who have the highest risk of death while awaiting a transplant. "We suggest focusing on amendments to organ distribution that decrease waitlist deaths with the least amount of additional sharing of livers and minimizes the distance the organs travel," recommends Dr. Washburn.
Sources: Wiley-Blackwell, AlphaGalileo Foundation.
Pharmaceuticals
FDA Wants To Make It Safer To Split Tablets
The practice of splitting tablets is nothing new. Countless people do so every day to save money or adjust dosages, but how does one know that each half - or portion - contains the needed amount of medication? Just because a tablet is scored - which is industry-speak for visible markings on the tablet coating - is not a guarantee that patients will get what they need.
Bioethics commission condemns Guatamalan syphilis research as unethical
Posted: 2011-08-30 14:52
Crossposted from Nature's news blog
Researchers knowingly violated ethical boundaries when they intentionally infected Guatamalan prisoners, mental health patients, and prostitutes with sexually transmitted diseases in a 1940s research project, a presidential commission concluded yesterday.
When the harrowing experiments came to light (see 'A shocking discovery'), President Barack Obama charged the President’s Commission for the Study of Bioethical Issues with investigating the matter. After picking through 125,000 pages of historical documents, the committee determined that the experiments were unethical even by the prevailing norms of the era, and that those who conducted the research actively sought to keep experiments out of the public eye.
It was also no accident that the research was performed in Guatemala, argued Amy Gutmann, chairwoman of the commission and president of the University of Pennsylvania. “Some of the people who were involved in this experiment explicitly said, ‘We could not do this in our own country’,” she said. “It was a foreign population that was seen as ethnically, racially, nationally different.”
“The only way you could continue doing this is to think of what you were working on as material as opposed to human subjects,” Gutmann added.
Continue reading on Nature's news blog.
FYI
New Tests for “Legal Marijuana,” “Bath Salts” and Other Emerging Designer Drugs
Released: 8/25/2011 1:00 PM EDT
Embargo expired: 8/30/2011 6:00 PM EDT
Source: American Chemical Society (ACS)
Michael Bernstein mailto:Bernsteinbernstein@acs.org 303-228-8532 (Aug. 25-Sept. 1)202-872-6042 (Before Aug. 25)Michael Woodsmailto:m_woods@acs.org?subject=Newswise 303-228-8532 (Aug. 25-Sept. 1)202-872-6293 (Before Aug. 25)
Description
Scientists today reported development of much needed new tests to help cope with a wave of deaths, emergency room visits and other problems from a new genre of designer drugs sold legally in stores and online that mimic the effects of cocaine, ecstasy and marijuana.
New tests will help law enforcement officials cope with a new genre of “bath salts” and other designer drugs that mimic the effects of cocaine, ecstasy and marijuana—a legal “high” in many states.
EMBARGOED FOR RELEASE: Tuesday, August 30, 6 p.m. Eastern Time
Note to journalists: Please report that this research was presented at a meeting of the American Chemical Society
Newswise — DENVER, Aug. 30, 2011 — Scientists today reported development of much needed new tests to help cope with a wave of deaths, emergency room visits and other problems from a new genre of designer drugs sold legally in stores and online that mimic the effects of cocaine, ecstasy and marijuana. They spoke at the 242nd National Meeting & Exposition of the American Chemical Society (ACS), being held here this week.
The reports, among more than 7,500 on the ACS agenda, focus on drugs sold as “bath salts,” “plant food,” “incense” and other products with colorful names, such as “Ivory Wave,” “Red Dove” and “legal marijuana.” They provide users with a high, but many have not yet been made illegal and are undetectable with current drug tests. In one presentation on these “legal highs,” a United Kingdom researcher reported a new method to trace the source of the substances in “bath salts.” In the other, a U.S. researcher discussed the challenges facing law enforcement and policy makers in regulating synthetic versions of marijuana.
Oliver Sutcliffe, Ph.D., and his collaborators reported the successful use of a method called isotope ratio mass spectrometry (IRMS) to determine who is making bath salts — drugs that can cause euphoria, paranoia, anxiety and hallucinations when snorted, smoked or injected — and which chemical companies supplied the raw materials. He and his co-workers are based at the University of Strathclyde and the James Hutton Institute in the U.K.
“With the new method, we could work backwards and trace the substances back to the starting materials,” said Sutcliffe. IRMS measures the relative amounts of an element’s different forms, or isotopic ratio. “This method was successful because the isotopic ratio of the starting material is transferred like a fingerprint through the synthesis,” he explained.
“Bath salts” first garnered major media attention in the U.K. in early 2010, and then became a problem in the U.S. These products are not in the supermarket soap aisle — they are sold on the Internet, on the street and in stores that sell drug paraphernalia. They are sold in small individual bags for as low as $20 each for the real purpose of providing a cheap, legal high.
The powders often contain mephedrone, which is a synthetic compound, structurally related to methcathinone, which is found in Khat — a plant that is illegal in many countries, including the U.K. and the U.S. Usually, that would mean that these compounds (and derivatives thereof) would be illegal in those countries too, but because the bath salts are labeled “not for human consumption,” they get around this restriction and other legislation governing the supply of medicines for human use. However, Florida and Louisiana — two hotspots of bath salts abuse — specifically banned the substances. U.K. officials banned the import of bath salts, which may lead some in the drug trade to set up clandestine labs on U.K. soil, said Sutcliffe. The new method provides law enforcement with a tool to track down these bath salts manufacturers.
In previous work, Sutcliffe developed the first pure reference standard for mephedrone, as well as the first reliable liquid chromatography test for the substance, which could be easily run in a typical law enforcement lab. The team is also developing a color-change test kit for mephedrone, which he estimates may be available by the end of the year.
In another presentation, Robert Lantz, Ph.D., from the Rocky Mountain Instrumental Laboratories, described another high that is legal in most of the U.S. — synthetic cannabinoids marketed as incense, a spice product or “legal marijuana” that give a high similar to marijuana without showing up in conventional drug tests.
“We can detect synthetic cannabinoids with modern analytical chemistry techniques, such as liquid or gas chromatography coupled to mass spectrometry, but these assays are too expensive for the 5,000-10,000 urine samples that most drug testing labs receive each day,” said Lantz. Most labs screen for drugs with less expensive antibody assays, but because the structures of these substances are so dissimilar, different antibodies would likely be required for many of them, driving up the cost of a more comprehensive test.
Synthetic cannabinoid abuse rose sharply in 2010, according to U.S. poison control centers, up to 2,863 compared to only 14 in 2009. About 200 synthetic cannabinoids exist, but the U.S. Drug Enforcement Agency (DEA) banned only five of those. A handful of states, such as Washington, Georgia and Colorado, banned five of them, but they are not always the same five that the DEA banned. “The states banned several specific compounds without a particular basis for their choices,” Lantz pointed out.
Colorado recently passed a law banning any substance that binds to a cannabinoid receptor in the human body. “The bill was well-intentioned, but technically, the new law not only covers synthetic cannabinoids, but also endocannabinoids, which are naturally occurring substances that the human body produces to regulate many normal processes,” said Lantz.
The American Chemical Society is a non-profit organization chartered by the U.S. Congress. With more than 163,000 members, ACS is the world’s largest scientific society and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.
# # #
Abstract (Dr. Sutcliffe):
The increase in the global abuse of synthetic cathinones has given rise to significant legal and analytical challenges in their identification and quantification - thus rapid methods of testing (especially in the field) are urgently required. This paper presents synthesis; characterisation; validated presumptive and quantitative methods for these substances (both in pure and adulterated samples) and a rapid, novel NMR screening technique for street samples containing components which cannot normally be detected using standard chromatographic methods.
Abstract (Dr. Lantz):
There is no end to human ingenuity. Unfortunately, this phrase even provides to be true when it comes to methods and means of getting high. Synthetic Cannabinoids, such as JWH-018 which is only one of many such substances (which is currently marketed as K2), and other substances such as Methylone (MDPV) and Mephedrone (which is currently marketed as “Bath Salts” or “Plant Food” respectively) present unique analytical chemistry challenges from a chromatographic point-of-view. Related challenges in terms of quantitation of these substances still exist. In the rush to make illegal and prosecute the possession and use of these substances, errors related the qualitative and quantitative reporting of these compounds can occur. This presentation will examine these challenges that exist and what lies ahead.
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