From the New England Journal of Medicine.
Boceprevir for Untreated Chronic HCV Genotype 1 Infection
F. Poordad and Others
Boceprevir for Previously Treated Chronic HCV Genotype 1 Infection
B.R. Bacon and Others
Posted by John Staples • March 30th, 2011
Blog
A Better Way to Unbind Prometheus? Boceprevir for the Treatment of Chronic Hepatitis C Infection
What do Mickey Mantle, Evel Knievel, and Pamela Anderson have in common? Infamy, certainly, but all three are also reported to have battled chronic hepatitis C virus (HCV) infection. And they aren’t alone: Including a sizable list of celebrities, it is estimated that 160 million people worldwide have the disease, putting them at risk of hepatic cirrhosis, hepatocellular carcinoma, and death. Current treatments with peginterferon plus ribavirin are poorly tolerated and result in sustained virologic response (SVR) rates below 50% in HCV genotype 1 infection. Some patients feel like the mythical Prometheus, their hands bound as they helplessly watch the virus ravage their liver day after day. Can anything more reliably loosen these chains?.... continue reading...
Related; Boceprevir; New Drugs for Hepatitis C on the Horizon
Difficult HCV Type Responds to Novel Protease Inhibitor
By Michael Smith, North American Correspondent, MedPage Today
Published: March 30, 2011
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.
Action Points
-------------------------------------
Note that rates of sustained virologic response associated with peginterferon–ribavirin therapy, the current treatment of choice for chronic infection with hepatitis C virus, remain below 50%.
Note that in these two studies, the addition of boceprevir, an experimental oral HCV-protease inhibitor, significantly improved response rates in both previously untreated and treated groups of patients.
Note that anemia is a significant concern with the use of this drug and may require the addition of erythropoietin.
In both untreated and previously treated hepatitis C patients, an investigational drug improved outcomes in a hard-to-treat type of the disease, researchers reported.
The drug -- boceprevir (Victrelis) -- significantly improved rates of sustained virologic response when added to standard therapy, compared with the standard therapy alone, according to two clinical trials reported in the March 31 issue of the New England Journal of Medicine.
Boceprevir is a protease inhibitor that directly targets genotype 1 of the virus -- one of two in clinical development -- and is the leading edge of a "new era of therapy for hepatitis C," according to Donald Jensen, MD, of the University of Chicago Medical Center, who contributed an editorial commenting on the studies in the same issue of the journal.
Jensen said that the protease inhibitors are a major advance in therapy for genotype 1 hepatitis C, which until now has relied on boosting the immune system, rather than attacking the virus directly. The drugs have little effect on other genotypes of hepatitis C.
The two industry-sponsored randomized, placebo-controlled trials had similar designs and were conducted by overlapping teams of investigators.
All patients had a four-week lead-in with peginterferon alfa-2b and ribavirin, the standard treatment. Then, in the control group, a placebo was added for another 44 weeks of treatment.
In a second group, treatment was guided by response: boceprevir was added for 24 weeks and if patients had detectable hepatitis C RNA between weeks eight and 24, the drug was continued for another 20 weeks.
Finally, a third group got boceprevir, combined with the standard therapy, for 48 weeks.
The endpoint for both studies was the proportion of patients who achieved a sustained virologic response, defined as undetectable hepatitis C RNA levels for 24 weeks after the end of therapy.
Among treatment naive patients in the so-called SPRINT-2 trial, the results were significantly better than placebo in both boceprevir arms, according to Fred Poordad, MD, of Cedars-Sinai Medical Center in Los Angeles, and colleagues.
In the cohort of 938 patients who were not black, they reported, 40% of those in the control group had a sustained virologic response.
On the other hand, the rate was 67% in the response-guided arm, and 68% in the fixed treatment arm -- both different at P<0.001 from the control group.
The 159 black patients were analyzed separately because blacks usually don't do as well when treated with standard therapy, the researchers noted.
In that cohort, 23% of the control patients had a sustained virologic response, compared with 42% in the response-guided arm and 53% in the fixed treatment arm. The differences from controls were significant at P=0.04 and P=0.004, respectively.
Meanwhile, a team led by Bruce Bacon, MD, of the Saint Louis University School of Medicine in St. Louis, Mo., conducted the so-called HCV RESPOND-2 trial among 438 patients previously treated with standard therapy.
Patients in the study had either failed to achieve a sustained virologic response on peginterferon and ribavirin or had reached that goal but relapsed.
Bacon and colleagues reported that the rate of sustained virologic response among patients in the control group was 21%, compared with 59% among patients getting response-guided therapy and 66% among those getting fixed duration treatment.
Both differences were significant at P<0.001.
Among patients who had never responded to therapy, the rates were 7% in the control group, 40% in the response-guided arm, and 52% in the fixed-duration boceprevir group.
Among those who had responded but relapsed, the comparable rates were 29%, 69%, and 75%, respectively, Bacon and colleagues reported.
One of the most common adverse effects of the drug was anemia, seen in both studies, and more than 40% of patients needed erythropoietin for up to 150 days.
Indeed, in the HCV RESPOND-2 trial, more than 8% of patients in the fixed-duration boceprevir group had a reduction in the hemoglobin level to less than 8.0 gm per deciliter, and 9% required blood transfusions, the researchers reported.
"This rate of anemia poses concerns," argued editorial writer Jensen, since without erythropoietin it could require adjusting the dosages of boceprevir, ribavirin, or both -- possibly reducing the rates of sustained virologic response.
Both studies were sponsored by Schering-Plough (now Merck).
Poordad reported financial links with Merck, Vertex, Abbott, Gilead, Achillion, Genentech, and Tibotec.
Bacon reported financial links with Gilead, Three Rivers Pharmaceuticals, Valeant, Vertex, Human Genome Sciences, Roche, Bristol-Myers Squibb, Wyeth, Romark Laboratories, Schering-Plough (now part of Merck), Novartis, and Isis.
In both cases, several authors reported being employed by or holding equity in the company.
Jensen reported financial links with Abbott, Boehringer-Ingelheim, BMS, Genentech/Roche, Roche Global, Merck, Pharmasset, Pfizer, Tibotec, Vertex, GlobeImmune, Medscape, Projects in Knowledge, Simpson Health Care, Focus Medical Communications, WebMD, and Practice Point Communications.
Primary source: New England Journal of Medicine
Source reference:
Poordad F, et al "Boceprevir for untreated chronic HCV genotype 1 infection" N Engl J Med 2011; 364: 1195-206.
Additional source: New England Journal of Medicine
Source reference:
Bacon BR, et al "Boceprevir for previously treated chronic HCV genotype 1 infection" N Engl J Med 2011; 364: 1207-1217.
Additional source: New England Journal of Medicine
Source reference:
Jensen DM "A new era of hepatitis C therapy begins" N Engl J Med 2011; 364: 1272-1274.
http://www.medpagetoday.com/InfectiousDisease/Hepatitis/25629
From EurekAlert
Public release date: 30-Mar-2011
Contact: Maria mseyrig1@hfhs.org
313-874-4039
Henry Ford Health System
Drug cocktail offers new hope for hepatitis C patients
A three-drug cocktail can eliminate the hepatitis C virus in patients far more effectively than the current two-drug regimen, according to researchers at Henry Ford Hospital.
"This study represents a remarkable advance and a potential cure for people with hepatitis C who have not responded to previous therapy," says co-author Stuart C. Gordon, M.D., section chief for the Division of Hepatology at Henry Ford Hospital.
"We will soon have a new standard of treatment for hepatitis C patients," says Dr. Gordon. "This study ushers in a new era of drug development that will provide a host of antiviral agents to treat hepatitis C, and we are now witnessing dramatic and rapid advances in how we will be able to treat these patients."
The results of the global study are in the March 31 issue of The New England Journal of Medicine.
At least 3.2 million Americans are infected with hepatitis C, a chronic viral disease affecting the liver. The Centers for Disease Control and Prevention estimates that more than 12,000 people die each year of liver disease and liver cancer associated with the hepatitis C virus.
Most people who are infected with hepatitis C remain without symptoms for years. When symptoms of advanced liver disease do occur, it is often too late to offer the current treatment regimens. The infection may lead to scarring of the liver (cirrhosis), liver cancer or the need for liver transplant.
The virus was previously spread through contact with infected blood products before 1990, and often via injection drug use or the sharing of straws during the use of cocaine. Among immigrants to the U.S. from Asian, African, Middle Eastern and Eastern European countries, the virus may have been transmitted via the use of non-sterile glass syringes used for vaccination purposes.
There is currently no vaccine for hepatitis C.
In the study, researchers randomly assigned patients to one of three groups. In all three groups, patients received peginterferon and ribavirin (the current standard of care) for four weeks. A control group (group 1) continued to receive only peginterferon–ribavirin for 44 additional weeks; group 2 received boceprevir plus peginterferon–ribavirin for 32 weeks, and patients with a detectable hepatitis C virus level at treatment week 8 received placebo plus peginterferon–ribavirin for an additional 12 weeks; and group 3 received boceprevir plus peginterferon–ribavirin for 44 weeks.
Boceprevir is a protease inhibitor, a new class of direct-acting antiviral agent that specifically targets and inhibits the replication of the hepatitis C virus.
Results showed the rate of sustained virologic response (loss of the virus) was significantly higher in the two boceprevir groups (group 2, 59%; group 3, 66%) than in the control group (21%).
Among patients with an undetectable hepatitis C virus level at treatment week 8, the rate of sustained virologic response was 86% after 32 weeks of triple therapy and 88% after 44 weeks of triple therapy. A sustained virologic response generally translates into a long-term eradication of virus, or cure.
"We can conclude that boceprevir, when added to peginterferon and ribavirin, leads to high rates of sustained virologic response in difficult-to-treat patients," explains Dr. Gordon.
In an accompanying article in the same issue of The New England Journal of Medicine, treatment of previously untreated hepatitis C patients with the same three-drug cocktail likewise showed significantly higher response rates than the current two drug regimen.
###
The study was funded by Schering-Plough (now Merck).
http://www.eurekalert.org/pub_releases/2011-03/hfhs-dco032311.php
Contact: Carrie Bebermeyer
bebermcl@slu.edu
314-977-8015
Saint Louis University
Game changer: Hepatitis C drug may revolutionize treatment
Saint Louis University investigator reports findings in New England Journal of Medicine
ST. LOUIS – The drug boceprevir helps cure hard-to-treat hepatitis C, says Saint Louis University investigator Bruce R. Bacon, M.D., author of the March 31 New England Journal of Medicine article detailing the study's findings. The results, which were first reported at the 61st annual meeting of the American Association for the Study of Liver Disease's last November, offer a brighter outlook for patients who have not responded to standard treatment.
Bacon, who is professor of internal medicine at Saint Louis University School of Medicine and co-principal investigator of the HCV RESPOND-2 study, studied the protease inhibitor boceprevir and found that it significantly increased the number of patients whose blood had undetectable levels of the virus.
"These findings are especially significant for patients who don't respond to initial treatment," said Bacon. "When the hepatitis C virus is not eliminated, debilitating fatigue and more serious problems can follow."
Hepatitis C is caused by a virus that is transmitted by contact with blood. The infection may initially be asymptomatic, but for patients who develop chronic hepatitis C infection, inflammation of the liver may develop, leading to fibrosis and cirrhosis (scarring of the liver), as well as other complications including liver cancer and death.
The prognosis varies for patients with chronic hepatitis C. With the current standard therapy, about half fully recover after an initial course of peginterferon and ribavirin anti-viral therapy that may last from six months to a year.
The remaining patients, known as non-responders, may improve with initial treatment but the virus is not eliminated, or may not respond to treatment at all. For this group, the only current option is to re-treat patients with the same or similar drugs, which increases the likelihood of severe treatment side-effects. In addition, researchers have found that the success of treatment depends on the major strain, or genotype, of hepatitis C that a patient has.
The HCV RESPOND-2 study looked at 403 patients with chronic hepatitis C infections with genotype one, the most difficult strain of the virus to treat, who still had significant levels of the virus after being treated with peginterferon and ribavirin, the standard hepatitis C treatment.
"These results are very exciting," Bacon said. "In this study, boceprevir helped cure significantly more patients in 36 weeks of therapy than did treatment with peginterferon and ribavirin alone."
A second study, HCV SPRINT-2, examined patients with hepatitis C with genotype one who had not yet been treated with the standard treatment. They, too, responded well to the drug.
Bacon calls the progress made in treating hepatitis C remarkable.
"We've gone from the discovery of the virus in 1989 to where we are now, 22 years later, when we have the ability to cure a large majority of those with hepatitis C," Bacon said. "It's a true success story."
"Drugs like boceprevir are going to revolutionize care of those with hepatitis C."
http://www.eurekalert.org/pub_releases/2011-03/slu-gc033011.php
Wednesday, March 30, 2011
Metastatic Cancers; SIR Liver Mets Respond to Radiation Microspheres
The group had previously shown that the same treatment delayed progression in primary liver cancer, which the FDA approved for humanitarian use in unresectable liver cancers. A similar Y-90 treatment was FDA approved for inoperable colorectal cancer as well.
The results in metastatic liver cancer weren't surprising, but were still important as the first prospective multicenter data on the strategy, commented co-author and program chair William Rilling, MD, of the Medical College of Wisconsin in Milwaukee.
The results in metastatic liver cancer weren't surprising, but were still important as the first prospective multicenter data on the strategy, commented co-author and program chair William Rilling, MD, of the Medical College of Wisconsin in Milwaukee.
By Crystal Phend, Senior Staff Writer, MedPage Today
Published: March 30, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
CHICAGO -- Targeted radiation delivered intra-arterially to refractory liver metastases among patients with metastatic colorectal cancer, neuroendocrine tumors, or other metastatic cancers appears to halt progression with little toxicity, according to results of an open-label phase II study.
Treatment with microscopic pellets of yttrium-90 (Y-90, TheraSphere) yielded a partial response or stable disease in 69.2% of these patients who failed prior chemotherapy regimens, Riad Salem, MD, MBA, of Northwestern University in Chicago, and colleagues found.
While the experimental therapy didn't eradicate any tumors, no severe adverse effects were seen in more than 1% of patients with intra-arterial Y-90, Salem's group reported here at the Society of Interventional Radiology meeting.
Mild fatigue and nausea were the most common side effects of the treatment, with grade 3 events limited to a 6% rate of pain and of elevated alkaline phosphatase levels indicating liver function problems.Action Points
---------------------------------------------------------
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Explain that targeted radiation delivered intra-arterially to refractory liver metastases among patients with metastatic colorectal cancer, neuroendocrine tumors, or other metastatic cancers appears to halt progression with little toxicity.
Note that no severe adverse effects were seen in more than 1% of patients with intra-arterial yttrium-90, and mild fatigue and nausea were the most common side effects of the treatment.
The group had previously shown that the same treatment delayed progression in primary liver cancer, which the FDA approved for humanitarian use in unresectable liver cancers. A similar Y-90 treatment was FDA approved for inoperable colorectal cancer as well.
The results in metastatic liver cancer weren't surprising, but were still important as the first prospective multicenter data on the strategy, commented co-author and program chair William Rilling, MD, of the Medical College of Wisconsin in Milwaukee.
Intra-arterial delivery of radiation -- akin to seed radiation implants for prostate cancer, but smaller and higher dose -- could change the standard of care for liver tumors, Salem suggested.
"We can do these sorts of very high level very potent therapies on an outpatient basis -- really a change in paradigm of cancer therapy compared with long infusions," he said at a press conference here.
His group conducted a single-arm, prospective, open-label trial in 151 patients with unresectable liver metastases refractory to or inappropriate for other systemic or targeted therapies. Most of these patients had primary colorectal (n=61) or neuroendocrine (n=44) cancers.
In the month prior to treatment, patients got imaging to map out the volume of tumor that would need to be treated and determine dose and catheterization route for delivery.
Patients got a total of 120 Gy of radiation in one or two doses from the glass encased microspheres, which Salem said did not travel beyond the liver in any cases.
The median progression-free survival was 2.8 months among colorectal cancer patients and 14.6 months among neuroendocrine cancer patients. Overall survival came in at a median 9.4 and 24.0 months, respectively.
Response rates in the overall study population were:
9.2% for partial response
60.0% for stable disease
30.8% for progressive disease
0.0% for complete response
Five deaths occurred among study participants, but none were judged to be treatment related.
Grade 4 adverse events included:
Four cases of elevated bilirubin
Five cases of liver dysfunction
Four cases of infection
Four cases of lymphopenia
Four cases of pain
Four cases of platelet abnormalities
Fatigue topped the list as the most common adverse event overall, at rates of 18% for grade 2 and 39% for grade 1. Salem called these "excellent tolerability and safety" results.
International multicenter phase III randomized controlled trials are getting under way with the treatment, he noted, including STOP-HCC in primary liver cancer to compare the sequence with sorafenib (Nexavar) to sorafenib alone and EPOCH in second-line treatment of liver metastases.
The study was sponsored by MDS Nordion.
Salem reported being a consultant for Nordion.
Rilling reported being a consultant for Navilyst, Cook Medical, DBO Innovations, B. Braun Medical, and Siemens Healthcare.
Primary source: Society of Interventional Radiology
Source reference:
Benson A, et al "Safety, response and survival outcomes of 90y radioembolization for liver metastases: Results from a 151-patient investigational device exemption multi-institutional study" SIR 2011;
Abstract 1.
Abstract 1.
EASL; Presidio's PPI-461, a novel HCV NS5A inhibitor preliminary results
Mar. 30, 2011 (Business Wire) -- Presidio Pharmaceuticals, Inc. announced today positive preliminary results from a Phase 1b clinical trial of PPI-461, a novel HCV NS5A inhibitor for the treatment of patients with chronic hepatitis C.
The PPI-461 phase 1b clinical trial reported here is a multiple ascending dose, randomized, blinded, placebo-controlled study in treatment-naïve adult hepatitis C patients with HCV genotype-1 infection; this trial is presently ongoing in the U.K., Denmark, and the United States. The study objectives are to assess the safety, tolerability, pharmacokinetics, and initial antiviral effects of PPI-461 during once-daily (QD) dosing at three dosing levels (50, 100, and 200 mg/day) for three days. Each dosing cohort
of 8 patients is randomized 6 (PPI-461):2 (placebo). Two dosing groups have completed study treatment to date; the third (200 mg) dosing group is ongoing.
The interim Phase 1b trial results indicate that PPI-461 has been well-tolerated, with no serious or severe adverse events and no modifications or premature discontinuations of study treatment. Among PPI-461 recipients there have been only transient clinical adverse events, of non-specific types commonly seen in clinical trials, with no dose-related or treatment-related patterns of specific adverse events or laboratory abnormalities.
Pharmacokinetic (PK) analyses of patients’ PPI-461 blood levels indicate that substantial blood levels of PPI-461 have been achieved rapidly and are dose proportional. Importantly, blood levels that are inhibitory for HCV replication have been maintained throughout the 24-hr inter-dose periods in the study patients.
Virologic data from the first two dosing groups indicate rapid and marked reductions in patients’ serum viral loads (HCV RNA levels), in both dosing groups, in the first two days of treatment. The 50 mg dosing group achieved a mean maximal HCV RNA reduction of 3.1 log10 IU/mL (5 of 6 patients), while the 100 mg group achieved a mean maximal HCV RNA reduction of 3.7 log10 IU/mL (6 of 6 patients). The mean maximal HCV RNA reduction for 4 Placebo treated patients was 0.3 log10 IU/mL. One patient in the 50 mg cohort had a negligible response to PPI-461(0.4 log10 IU/mL HCV RNA reduction). This patient entered the study with highly resistant virus, as evidenced by NS5A resistance substitutions (L31M, Y93N, L28F, R30N) detected at high levels in pre-treatment sera. Such a patient would be expected to have minimal efficacy with any NS5A inhibitor, since these agents share common key resistance mutations, as will be reported in a Presidio presentation at the 2011 annual meeting of the European Association for the Study of Liver Disease (EASL) in Berlin on April 2nd (R. Colonno et al., poster #1199).
Efficacy data for individual patients receiving active PPI-461 treatment in the first two dosing cohorts in the Phase 1b trial are presented in Table 1:
Table 1
HCV RNA Reduction log10 IU/mL
Dose\Patient .........1....... 2....... 3 .........4......... 5........ 6
50 mg,
.................... 0.4*......... 2.6 .....2.7..... 3.3 ....3.4..... 3.5
100 mg ..........2.6.......... 3.7..... 3.7..... 3.8..... 4.0..... 4.1
*Four NS5A-specific linked mutations in 100% of virus population at study entry ..
“These positive clinical data for PPI-461 in hepatitis C patients further support the inclusion of NS5A inhibitors in clinical development of novel combination therapies. Such future combination therapies are expected to substantially improve patient outcomes and should help stem the rising incidence of HCV-associated severe liver disease and premature mortality,” said Nathaniel A. Brown, M.D., Presidio’s Chief Medical Officer.
The final results of the completed Phase 1b trial of PPI-461 will be submitted for presentation at a scientific meeting later this year.
About Presidio’s HCV NS5A Inhibitors
Inhibitors of the HCV NS5A protein represent an exciting, highly potent class that is mechanistically distinct from other classes of direct-acting HCV antivirals that target the viral protease or replicase (polymerase).
PPI-461 is the first in a series of novel and selective HCV NS5A inhibitors discovered by Presidio Pharmaceuticals. Presidio’s NS5A candidates are selected from numerous internal discovery leads, based on their potent activity against all major HCV genotypes and their potential for once-daily dosing with good tolerance. A Presidio presentation at the 2011 annual meeting of EASL in Berlin on April 2nd (R. Colonno et al., Poster #1200) will highlight the preclinical profile of three other novel NS5A inhibitors in development by Presidio, which derive from distinct chemical series.
About Presidio
Presidio Pharmaceuticals, Inc. is a San Francisco-based clinical stage specialty pharmaceutical company dedicated to the discovery and development of small-molecule antiviral therapeutics for novel and validated targets. For more information, please visit our website at: http://www.presidiopharma.com/ .
Presidio Pharmaceuticals, Inc.
Omar K. Haffar, PhD, 415-655-7561
omar@presidiopharma.com
The PPI-461 phase 1b clinical trial reported here is a multiple ascending dose, randomized, blinded, placebo-controlled study in treatment-naïve adult hepatitis C patients with HCV genotype-1 infection; this trial is presently ongoing in the U.K., Denmark, and the United States. The study objectives are to assess the safety, tolerability, pharmacokinetics, and initial antiviral effects of PPI-461 during once-daily (QD) dosing at three dosing levels (50, 100, and 200 mg/day) for three days. Each dosing cohort
of 8 patients is randomized 6 (PPI-461):2 (placebo). Two dosing groups have completed study treatment to date; the third (200 mg) dosing group is ongoing.
The interim Phase 1b trial results indicate that PPI-461 has been well-tolerated, with no serious or severe adverse events and no modifications or premature discontinuations of study treatment. Among PPI-461 recipients there have been only transient clinical adverse events, of non-specific types commonly seen in clinical trials, with no dose-related or treatment-related patterns of specific adverse events or laboratory abnormalities.
Pharmacokinetic (PK) analyses of patients’ PPI-461 blood levels indicate that substantial blood levels of PPI-461 have been achieved rapidly and are dose proportional. Importantly, blood levels that are inhibitory for HCV replication have been maintained throughout the 24-hr inter-dose periods in the study patients.
Virologic data from the first two dosing groups indicate rapid and marked reductions in patients’ serum viral loads (HCV RNA levels), in both dosing groups, in the first two days of treatment. The 50 mg dosing group achieved a mean maximal HCV RNA reduction of 3.1 log10 IU/mL (5 of 6 patients), while the 100 mg group achieved a mean maximal HCV RNA reduction of 3.7 log10 IU/mL (6 of 6 patients). The mean maximal HCV RNA reduction for 4 Placebo treated patients was 0.3 log10 IU/mL. One patient in the 50 mg cohort had a negligible response to PPI-461(0.4 log10 IU/mL HCV RNA reduction). This patient entered the study with highly resistant virus, as evidenced by NS5A resistance substitutions (L31M, Y93N, L28F, R30N) detected at high levels in pre-treatment sera. Such a patient would be expected to have minimal efficacy with any NS5A inhibitor, since these agents share common key resistance mutations, as will be reported in a Presidio presentation at the 2011 annual meeting of the European Association for the Study of Liver Disease (EASL) in Berlin on April 2nd (R. Colonno et al., poster #1199).
Efficacy data for individual patients receiving active PPI-461 treatment in the first two dosing cohorts in the Phase 1b trial are presented in Table 1:
Table 1
HCV RNA Reduction log10 IU/mL
Dose\Patient .........1....... 2....... 3 .........4......... 5........ 6
50 mg,
.................... 0.4*......... 2.6 .....2.7..... 3.3 ....3.4..... 3.5
100 mg ..........2.6.......... 3.7..... 3.7..... 3.8..... 4.0..... 4.1
*Four NS5A-specific linked mutations in 100% of virus population at study entry ..
“These positive clinical data for PPI-461 in hepatitis C patients further support the inclusion of NS5A inhibitors in clinical development of novel combination therapies. Such future combination therapies are expected to substantially improve patient outcomes and should help stem the rising incidence of HCV-associated severe liver disease and premature mortality,” said Nathaniel A. Brown, M.D., Presidio’s Chief Medical Officer.
The final results of the completed Phase 1b trial of PPI-461 will be submitted for presentation at a scientific meeting later this year.
About Presidio’s HCV NS5A Inhibitors
Inhibitors of the HCV NS5A protein represent an exciting, highly potent class that is mechanistically distinct from other classes of direct-acting HCV antivirals that target the viral protease or replicase (polymerase).
PPI-461 is the first in a series of novel and selective HCV NS5A inhibitors discovered by Presidio Pharmaceuticals. Presidio’s NS5A candidates are selected from numerous internal discovery leads, based on their potent activity against all major HCV genotypes and their potential for once-daily dosing with good tolerance. A Presidio presentation at the 2011 annual meeting of EASL in Berlin on April 2nd (R. Colonno et al., Poster #1200) will highlight the preclinical profile of three other novel NS5A inhibitors in development by Presidio, which derive from distinct chemical series.
About Presidio
Presidio Pharmaceuticals, Inc. is a San Francisco-based clinical stage specialty pharmaceutical company dedicated to the discovery and development of small-molecule antiviral therapeutics for novel and validated targets. For more information, please visit our website at: http://www.presidiopharma.com/ .
Presidio Pharmaceuticals, Inc.
Omar K. Haffar, PhD, 415-655-7561
omar@presidiopharma.com
Hall Of Shame; Pharmaceutical Companies and HCV oh my!
Hall Of Shame
Pharmaceutical Companies and HCV
Remember When ????
In November of 2010 Roche was fined for offering money to a nurse working at a undisclosed clinic. Kate Hagan from age.com writes "Drug company Roche has been fined $200,000 for offering to fund a nurse's position at a health service - depending on how many patients were treated with its hepatitis C drug Pegasys"The drug company has two fines under (two different occasions) the Medicines Australia code of conduct for the maximum of 200,000 dollars. This summer a French doctor working as a consultant for "Human Genome Sciences Inc. was charged by the U.S. with insider-trading for allegedly tipping off a hedge fund about negative results of Albuferon drug trials."
In October of the same year Sam Waksal, the former CEO of ImClone Systems, whose insider trading lead to spending time in prison along with Martha Stewart, remember? Announced a new enterprise; "Waksal said his drug company Kadmon Pharmaceuticals has bought the privately held Three Rivers Pharmaceuticals, and that its treatments for hepatitis C, infections and cancer will be the backbone of his new enterprise".
Let's not forget the list published on the 384 doctors and healthcare professionals who were paid by pharmaceutical companies to promote their drugs. They "Drew Payments From Drug Companies" for the amount of no less then $100,000 published @ ProPublicas website: This list covered "Top Earners from 2009 and early 2010"
The Johnson & Johnson Dilemma;
Johnson & Johnson who is in late stage trials of hepatitis C drug TMC435 and as we know has a hand in Vertex/Johnson & Johnson/Mitsubishi Tanabe's drug telaprevir, sure has seen better days.
Lets begin with their plant in Las Piedras, Puerto the FDA’s website back in November found these problems; as noted here, "Distribution of drugs that failed quality requirements, a failure to identify product defects during routine testing, failure to detect incorrect expiration dates on drug labels, failure to adequately investigate product problems, failure to follow laboratory controls and inadequate training of lab staff..
Thus far the company has recalled millions of bottles of Tylenol, Motrin and other products manufactured in Puerto Rico."
Ft. Washington, Pennsylvania Plant The Back Story;
Recalls; January 14, 2011
The Januray recall affected certain lots of Tylenol, Benadryl and Sudafed products because of insufficient cleaning procedures, though the company does not believe that quality was impacted. The company also recalled certain lots of Rolaids tablets because they do not include certain labeling information. All of the products were made at the company's plant in Fort Washington, Pa., before it was shuttered in April following a Food and Drug Administration investigation. FDA inspectors found a slew of manufacturing problems at the plant, including equipment covered with thick layers of dust and others held together with duct tape. J & J issued several recalls related to the problems, the largest of which involved more than 135 million bottles of infants' and children's Tylenol and other medicines.
The Shut Down
In may McNeil Consumer products shut down the Ft. Washington factory, FDA found these problems, quoted from this article "Among other problems, FDA inspectors said some manufacturing equipment was covered with dust, and others was held together by duct tape. The company did not have laboratory facilities to test drug ingredients. The agency says its inspectors found bacterial contamination in some raw materials. They declined to name the type of bacteria, saying they "didn't have enough information in yet. The FDA says there is no indication of contamination in the finished products."
From Pharmalot ; The plant is now being retooled and under careful watch as part of a consent decree (see this, this and this).
Just yesterday Reuters reported that Johnson & Johnson, is recalling more of its over-the-counter Tylenol products. The company said it was recalling over 700,000 bottles or packages of Tylenol and other consumer medicines made at a now-closed plant, the latest in a litany of recalls by the company.
The company product was made at its Fort Washington, Pennsylvania plant before J & J closed the facility in April 2010.
Again, From Pharmalot; For The Record, Another Johnson & Johnson Recall
On March 28 Johnson & Johnson's Ethicon unit is recalling a group of medical drainage products because of concerns about the sterility of the products.
Misleading Letter
A jury in South Carolina on March 25 found Johnson & Johnson's pharmaceutical unit, Ortho-McNeil-Janssen, guilty of misleading doctors about the safety and effectiveness of the anti-psychotic drug Risperdal. It seems a Johnson & Johnson unit violated consumer-protection laws by sending South Carolina doctors a misleading letter about the safety and effectiveness of the antipsychotic drug Risperdal.
From The Famous TV News Show 60 Minutes
The Tale of a Whistleblower: How One Pharmaceutical Giant Was Brought to Its Knees
November of 2010 we discovered that one of the world’s largest drug manufacturers, a subsidiary of GlaxoSmithKline, wasn’t really looking after our well being at all when it distributed adulterated drugs. However, it appears they had an eagle eye on the money. They would’ve likely gotten away with what appears to be gross negligence, too, were it not for one whistleblower. More than likely medications tainted with bacteria, labeled incorrectly, or not the correct strength would have continued to make it to our pharmacies. However, thanks to a tip from a company insider, Cheryl Eckard, a federal investigation ensued and Glaxo has had to pay up
Pharmaceutical Hall Of Shame 2011
The lawsuit was initially filed by former BMS employees - Michael Wilson, who was a sales rep; Lucius Allen, who was a cardiovascular metabolic risk specialist; and Eve Allen, who was an integrated health manager. They alleged the drugmaker instructed its reps to woo docs with expensive meals; theater and concert tickets; honoraria; liquor; gift cards; golf outings; all-expense-paid trips to resorts and samba dances (for Hispanic physicians) to induce them to prescribe more meds. One popular freebie: suites at the Staples Center to watch Los Angeles Laker basketball games, food included.
An FDA chemist named Cheng Yi Liang was charged today by the US Securities and Exchange Commission with insider trading on confidential info about upcoming announcements of 27 different FDA approval decisions involving 19 publicly traded companies and generated more than $3.6 million in illegal profits for himself. And would you believe that he avoided incurring any losses?
Some of the FDA announcements involved approval of new drugs while others concerned were negative decisions. In each instance, the SEC says he traded in the same direction as the announcement, but worked hard to disguise his work. Beginning in July 2006, Liang traded in seven brokerage accounts, including six listed in the names of other people, including his 25-year-old (who was also charged) and his 84-year-old mother who lives in China......
Sonova Holding AG (SOON) said its chairman, chief executive and finance chief are resigning their posts after a delayed profit warning prompted an investigation into possible insider trading at the Swiss hearing-aid maker.
Chief Executive Officer Valentin Chapero and Oliver Walker, Sonova’s chief financial officer, have handed in their resignations, the Staefa, Switzerland-based company said in a statement today. Chairman Andy Rihs will also step down from his post while remaining on the board, Sonova said. The board appointed Robert Spoerry as its new chairman. Alexander Zschokke will be interim CEO.
Merck The Company Behind The Investigational HCV drug Boceprevir
By GOSIA WOZNIACKA, Associated Press
Associated Press March 29, 2011 06:23 PM Copyright Associated Press.
Tuesday, March 29, 2011
Company officials failed to alert residents and collect data about groundwater, air and soil contaminated with cancer-causing chemicals from a Central California manufacturing plant owned by a former subsidiary of drug maker Merck & Co., lawyers for nearby residents told jurors Tuesday in closing arguments of a lawsuit.
Attorney Mick Marderosian, who represents 2,000 plaintiffs, said the defendants — Merck & Co., Amsted Industries Inc., Meadowbrook Water Co. and Baltimore Aircoil Co. Inc. — didn't alert a Merced housing community directly across the street from the plant about contamination from hexavalent chromium, the chemical made famous in the film "Erin Brockovich."
Triad Prep Pads;
By JoNel Aleccia
Health writer
updated 3/28/2011 6:30:10 PM ET 2011-03-28T22:30:10
The federal Food and Drug Administration is asking a Wisconsin firm tied to infections and death blamed on contaminated medical wipes to voluntarily stop making and distributing its drug products, msnbc.com has learned.
The move is aimed at halting operations at H & P Industries Inc., which does business as the Triad Group of Hartland, Wis., said Michael C. Rogers, the FDA's acting director of the Office of Regional Operations. It comes at the conclusion of an intense, week-long inspection that concluded Monday, Rogers said.
"We have evidence that shows this firm made and distributed products with a variety of opportunistic pathogens," Rogers said.
In a statement, H&P Industries officials confirmed that they had been contacted by FDA about "manufacturing of products not covered by previous recalls." A company spokeswoman, Christy Maginn, would not say whether the firm will stop operations.
"At this time, they're still in discussions with FDA," Maginn said.
The cease-and-desist request follows a series of msnbc.com news reports about inspections at the Triad Group plant and massive recalls of alcohol prep wipes, povidone iodine prep wipes and lubricating jelly all suspected of bacterial contamination.
The alcohol wipes, which were recalled for potential contamination with the bacteria Bacillus cereus, have been blamed for several serious infections and the death of a 2-year-old boy in Houston.
The Back Story
H & P Industries, the parent company of the Triad Group, has issued a voluntary recall of all lots of providine idodine prep pads
March 19 2011
,
,
New Recall: All lots of povidine iodine prep pads manufactured by H & P Industries Inc.
As of March 15th
H & P Industries, the parent company of the Triad Group, has issued a voluntary recall of all lots of providine idodine prep pads. The notice from H & P stated the pads may be contaminated with "Elizabethkingia meningoseptica", an organism that has caused rare but serious infections in humans, including, pneumonia in patients on ventilators and necrotizing fasciitis, more commonly known as flesh-eating bA and meningitis in newborn infants. As noted in the press release from H & P now on the FDA's website the new recalled prep pads include povidine iodine prep pads made by H&P Industries packaged under the names Cardinal Health, Medical Specialties, VHA, Triad, Triad Plus, North Safety and Total Resources.
MSNBC published this article ; FDA not ready to act on tainted wipes, despite new recall .
"Agency 'very concerned' about iodine pads tainted with dangerous bacteria, official says"
See The Press Release From H & P Here
Feb 22 2011
USA: FDA knew of problems with Triad's tainted alcohol wipes Roche said "Triad pads are distributed with several drugs including the Boniva bone-building drug and hepatitis C treatment Pegasys."
Merck said "Triad pads were distributed with Pegintron, a treatment for hepatitis C, and a related drug, Intron A, outside the U.S. Merck said drugs distributed in the U.S. aren't affected."
Merck issued a warning about the recalled pads to customers who use Pegintron (peginterferon alfa-2b) single dose RediPen and Pegintron vials for markets in Europe, Asia Pacific (excluding Japan), Latin America and Canada, and Intron A (interferon alfa-2b) Multidose RediPen and Intron A solution vials for markets in Europe, Asia Pacific (excluding Japan) and Latin America. Triad: http://triad-group.net/
Off The Cuff
From The Wall Street Journal
U.S. NEWS MARCH 29, 2011 Secrets of the System
By JOHN CARREYROU And TOM MCGINTY
PORTLAND, Ore.—Dr. Vishal James Makker had already operated on Ronald Johnson's spine six times in less than two years, but he had some grim news for the former machine-tool operator: X-rays showed Mr. Johnson needed a seventh surgery.
Mr. Johnson, 62 years old, says he had felt progressively worse after each operation. He told the doctor he was done with surgeries.
Dr. Makker took a second look at the X-rays and changed his tune, Mr. Johnson recalls. "Actually, you're going to be all right," he says Dr. Makker told him, adding that he had been looking at the films wrong.
At that moment, Mr. Johnson became the latest in a string of patients to grow suspicious about multiple surgeries performed on them by Dr. Makker, a handsome, 41-year-old neurosurgeon with a charming bedside manner..
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Pharmalot is a great site to read while you drink that morning cup of coffee, what a way to start the day .
Pharmalot offers ; "Commentary on the pharmaceutical industry and related litigation."
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I would like to mention how grateful I am to both J & J and Merck for bringing us Telaprevir/Boceprevir.
Although the pharmaceutical industry as a whole have their problems, I personally hope these two drug companies remain financially stable and continue to embark on new investigational drugs to treat HCV.
I continue to have faith in both companies and assume/pray they will continue in their effort to find a cure for HCV.
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Well, also folks we have; Achillion ACH-1625 , PSI-938 and PSI-7977 and other drugs making their way down the pipeline, waiting for more good news from the EASL meeting.
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Thats My Bottom Line
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Enjoy The Day !
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Well, also folks we have; Achillion ACH-1625 , PSI-938 and PSI-7977 and other drugs making their way down the pipeline, waiting for more good news from the EASL meeting.
.
Thats My Bottom Line
.,
Enjoy The Day !
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Achillion ACH-1625 hepatitis drug shows promise in mid-stage trial
UPDATE 2-Achillion hepatitis drug shows promise in mid-stage trial
Wed Mar 30, 2011 8:52am EDT
* Says 75-81 pct patients showed anitviral activity
* Plans to start a trial testing ACH-1625, ACH-2928 in 2012
* Shares up 4 pct in pre-market trade (Adds background, updates share movement)
March 30 (Reuters) - Achillion Pharmaceuticals Inc said its experimental lead drug to treat chronic hepatitis C infection showed strong antiviral activity in a mid-stage trial, sending its shares up 4 percent in pre-market trade.
The company said 75-81 percent patients who took ACH-1625 in combination with current standard of care (SoC)-- Roche Holding AG's Pegasys and generic antiviral pill ribavirin -- showed potent antiviral activity in the fourth week.
The drug showed a promising safety and tolerability profile, Achillion said.
Worldwide, more than 170 million people are suffering from HCV and the American Association of Liver Disease estimates that up to 80 percent of individuals become chronically infected following exposure to the virus.
The mid-stage trial involving 64 patients tested three doses of ACH-1625 given once daily or a dummy drug in combination with current SoC treatment for four weeks.
"We look forward to selecting two of these doses and beginning the second segment of the trial, dosing ACH-1625 with SoC over 12 weeks," Chief Medical Officer Elizabeth Olek said.
The company expects to report complete early virology response data from this trial by the end of this year.
Also, it expects to start a trial evaluating ACH-1625 in combination with its other HCV drug ACH-2928 in 2012.
Shares of the company were up 30 cents at $7.35 in pre-market trade. They closed at $7.05 on Tuesday on Nasdaq. (Reporting by Anand Basu in Bangalore; Editing by Don Sebastian; Editing by Maju Samuel)
http://www.reuters.com/article/2011/03/30/achillion-idUSL3E7EU1OT20110330?feedType=RSS&feedName=governmentFilingsNews
Wed Mar 30, 2011 8:52am EDT
* Says 75-81 pct patients showed anitviral activity
* Plans to start a trial testing ACH-1625, ACH-2928 in 2012
* Shares up 4 pct in pre-market trade (Adds background, updates share movement)
March 30 (Reuters) - Achillion Pharmaceuticals Inc said its experimental lead drug to treat chronic hepatitis C infection showed strong antiviral activity in a mid-stage trial, sending its shares up 4 percent in pre-market trade.
The company said 75-81 percent patients who took ACH-1625 in combination with current standard of care (SoC)-- Roche Holding AG's Pegasys and generic antiviral pill ribavirin -- showed potent antiviral activity in the fourth week.
The drug showed a promising safety and tolerability profile, Achillion said.
Worldwide, more than 170 million people are suffering from HCV and the American Association of Liver Disease estimates that up to 80 percent of individuals become chronically infected following exposure to the virus.
The mid-stage trial involving 64 patients tested three doses of ACH-1625 given once daily or a dummy drug in combination with current SoC treatment for four weeks.
"We look forward to selecting two of these doses and beginning the second segment of the trial, dosing ACH-1625 with SoC over 12 weeks," Chief Medical Officer Elizabeth Olek said.
The company expects to report complete early virology response data from this trial by the end of this year.
Also, it expects to start a trial evaluating ACH-1625 in combination with its other HCV drug ACH-2928 in 2012.
Shares of the company were up 30 cents at $7.35 in pre-market trade. They closed at $7.05 on Tuesday on Nasdaq. (Reporting by Anand Basu in Bangalore; Editing by Don Sebastian; Editing by Maju Samuel)
http://www.reuters.com/article/2011/03/30/achillion-idUSL3E7EU1OT20110330?feedType=RSS&feedName=governmentFilingsNews
Tuesday, March 29, 2011
High-dose regimen of Lipitor may have a slightly increased risk of developing type 2 diabetes
By Amy Norton – Mon Mar 28, 4:25 pm ET
NEW YORK (Reuters Health) – People on a high-dose regimen of the cholesterol drug Lipitor may have a slightly increased risk of developing type 2 diabetes -- particularly if they have several of the classic diabetes risk factors, a study published Monday finds.
A number of studies have linked Lipitor (known generically as atorvastatin) and other cholesterol-lowering statin drugs to a small increase in users' risk of diabetes.
This latest study, based on data from three large clinical trials, strengthens evidence of a connection.
But it also suggests that the risk may largely exist among people who also have the well-known risk factors for type 2 diabetes -- including excess weight, high blood sugar, elevated triglycerides (a type of blood fat) and high blood pressure.
Those four factors appear "very good at distinguishing people at high or low risk for developing new-onset diabetes with atorvastatin," lead researcher Dr. David D. Waters, of the University of California at San Francisco, told Reuters Health in an email.
So managing those risk factors -- by shedding excess pounds, for example -- would be important for curbing any extra diabetes risk, Waters said.
He also stressed that the diabetes risk tied to statins is small.
"An important point," Waters said, "is that the risk of developing new-onset diabetes and its complications (is) greatly outweighed by the benefit of statins in reducing cardiac death, heart attack and stroke."
The findings, published in the Journal of the American College of Cardiology, are based on data from three clinical trials comparing high-dose atorvastatin (80 milligrams) with either a lower dose statin or placebo pills in people with cardiovascular disease.
In the trial with the placebo group, the study found, atorvastatin users had a higher risk of developing type 2 diabetes over 5 years. Just under 9 percent did, versus 6 percent of the placebo group.
That trial included 3,800 adults who were diabetes-free at the outset; all had a history of stroke or "mini" strokes known as transient ischemic attacks.
When Waters and his colleagues accounted for a number of other factors -- like age, weight and smoking habits -- atorvastatin use was linked to a 37 percent increase in the odds of developing diabetes, versus the placebo.
But a closer look showed that the extra risk appeared limited to patients with at least two of the "big-four" risk factors for diabetes.
Of patients with all four risk factors, nearly half of atorvastatin users -- 26 of 56 -- developed diabetes, versus just over 20 percent of the placebo group (11 of 52 participants).
Waters' team found no strong connection between high-dose atorvastatin and diabetes risk in the other two trials.
In one, researchers compared 80 mg of atorvastatin against 20 mg of simvastatin (Zocor) in nearly 7,500 heart attack sufferers who were free of diabetes. Over 5 years, 6.4 percent of atorvastatin users developed diabetes, as did 5.6 percent of simvastatin users.
The third trial compared high-dose atorvastatin against a 10 mg dose of the drug in people with stable heart disease. Of the 7,600 who were free of diabetes to start, 9 percent in the high-dose group and 8 percent in the low-dose group developed diabetes over 5 years.
Statins are not the only drugs that have been linked to diabetes risk. Certain high blood pressure treatments (beta-blockers and thiazide diuretics), niacin (sometimes used to lower cholesterol and triglycerides) and glucocorticoids are among the others.
In most of those cases, the reason for the risk appears to be the drugs' effect on the body's ability to control blood sugar.
In contrast, it's not yet clear why statins would contribute to diabetes, Waters said.
He and his colleagues suggest that doctors might want to carefully monitor atorvastatin users for diabetes. But, they write, the benefits of the drug "clearly outweigh" the risks for people with heart disease or a history of stroke.
People without heart disease or prior stroke may be able to first try diet changes and exercise alone for lowering their cholesterol.
Waters and other researchers on the study have financial ties to Lipitor-maker Pfizer Inc. as well as other drug companies. Three co-researchers are Pfizer employees.
SOURCE: http://bit.ly/d1cHYE
Journal of the American College of Cardiology, online March 28, 2011
NEW YORK (Reuters Health) – People on a high-dose regimen of the cholesterol drug Lipitor may have a slightly increased risk of developing type 2 diabetes -- particularly if they have several of the classic diabetes risk factors, a study published Monday finds.
A number of studies have linked Lipitor (known generically as atorvastatin) and other cholesterol-lowering statin drugs to a small increase in users' risk of diabetes.
This latest study, based on data from three large clinical trials, strengthens evidence of a connection.
But it also suggests that the risk may largely exist among people who also have the well-known risk factors for type 2 diabetes -- including excess weight, high blood sugar, elevated triglycerides (a type of blood fat) and high blood pressure.
Those four factors appear "very good at distinguishing people at high or low risk for developing new-onset diabetes with atorvastatin," lead researcher Dr. David D. Waters, of the University of California at San Francisco, told Reuters Health in an email.
So managing those risk factors -- by shedding excess pounds, for example -- would be important for curbing any extra diabetes risk, Waters said.
He also stressed that the diabetes risk tied to statins is small.
"An important point," Waters said, "is that the risk of developing new-onset diabetes and its complications (is) greatly outweighed by the benefit of statins in reducing cardiac death, heart attack and stroke."
The findings, published in the Journal of the American College of Cardiology, are based on data from three clinical trials comparing high-dose atorvastatin (80 milligrams) with either a lower dose statin or placebo pills in people with cardiovascular disease.
In the trial with the placebo group, the study found, atorvastatin users had a higher risk of developing type 2 diabetes over 5 years. Just under 9 percent did, versus 6 percent of the placebo group.
That trial included 3,800 adults who were diabetes-free at the outset; all had a history of stroke or "mini" strokes known as transient ischemic attacks.
When Waters and his colleagues accounted for a number of other factors -- like age, weight and smoking habits -- atorvastatin use was linked to a 37 percent increase in the odds of developing diabetes, versus the placebo.
But a closer look showed that the extra risk appeared limited to patients with at least two of the "big-four" risk factors for diabetes.
Of patients with all four risk factors, nearly half of atorvastatin users -- 26 of 56 -- developed diabetes, versus just over 20 percent of the placebo group (11 of 52 participants).
Waters' team found no strong connection between high-dose atorvastatin and diabetes risk in the other two trials.
In one, researchers compared 80 mg of atorvastatin against 20 mg of simvastatin (Zocor) in nearly 7,500 heart attack sufferers who were free of diabetes. Over 5 years, 6.4 percent of atorvastatin users developed diabetes, as did 5.6 percent of simvastatin users.
The third trial compared high-dose atorvastatin against a 10 mg dose of the drug in people with stable heart disease. Of the 7,600 who were free of diabetes to start, 9 percent in the high-dose group and 8 percent in the low-dose group developed diabetes over 5 years.
Statins are not the only drugs that have been linked to diabetes risk. Certain high blood pressure treatments (beta-blockers and thiazide diuretics), niacin (sometimes used to lower cholesterol and triglycerides) and glucocorticoids are among the others.
In most of those cases, the reason for the risk appears to be the drugs' effect on the body's ability to control blood sugar.
In contrast, it's not yet clear why statins would contribute to diabetes, Waters said.
He and his colleagues suggest that doctors might want to carefully monitor atorvastatin users for diabetes. But, they write, the benefits of the drug "clearly outweigh" the risks for people with heart disease or a history of stroke.
People without heart disease or prior stroke may be able to first try diet changes and exercise alone for lowering their cholesterol.
Waters and other researchers on the study have financial ties to Lipitor-maker Pfizer Inc. as well as other drug companies. Three co-researchers are Pfizer employees.
SOURCE: http://bit.ly/d1cHYE
Journal of the American College of Cardiology, online March 28, 2011
J&J recalling more Tylenol from closed plant
Tue Mar 29, 3:52 pm ET
NEW YORK (Reuters) – Johnson & Johnson said it was recalling more than 700,000 bottles or packages of Tylenol and other consumer medicines made at a now-closed plant, the latest in a litany of recalls by the company.
J&J's McNeil Consumer Healthcare unit recalled one lot of Tylenol 8 Hour Extended Release Caplets, or 34,056 bottles, from retailers, the company said.
The company cited a musty odor that has prompted many other J&J recalls. The product was made at its Fort Washington, Pennsylvania plant before J&J closed the facility in April 2010.
Separately, McNeil added 10 lots of other products, amounting to 717,696 bottles or packages, to a wholesale level recall it initiated on January 14. Those products included various forms of pain reliever Tylenol, as well as allergy drug Benadryl and cough/cold medicine Sudafed.
In that recall, McNeil said it was taking precautions after a review of records found instances where equipment cleaning procedures were insufficient or cleaning was not adequately documented, although it said it was unlikely to have hurt product quality.
J&J has recalled more than 300 million bottles and packages of adult and children's consumer medicines in the past 15 months. Although no injuries have been linked to the recalls, they have sullied J&J's reputation, pressured its share price and sparked Congressional investigations.
(Reporting by Lewis Krauskopf; editing by Andre Grenon)
http://news.yahoo.com/s/nm/20110329/hl_nm/us_johnsonandjohnson
NEW YORK (Reuters) – Johnson & Johnson said it was recalling more than 700,000 bottles or packages of Tylenol and other consumer medicines made at a now-closed plant, the latest in a litany of recalls by the company.
J&J's McNeil Consumer Healthcare unit recalled one lot of Tylenol 8 Hour Extended Release Caplets, or 34,056 bottles, from retailers, the company said.
The company cited a musty odor that has prompted many other J&J recalls. The product was made at its Fort Washington, Pennsylvania plant before J&J closed the facility in April 2010.
Separately, McNeil added 10 lots of other products, amounting to 717,696 bottles or packages, to a wholesale level recall it initiated on January 14. Those products included various forms of pain reliever Tylenol, as well as allergy drug Benadryl and cough/cold medicine Sudafed.
In that recall, McNeil said it was taking precautions after a review of records found instances where equipment cleaning procedures were insufficient or cleaning was not adequately documented, although it said it was unlikely to have hurt product quality.
J&J has recalled more than 300 million bottles and packages of adult and children's consumer medicines in the past 15 months. Although no injuries have been linked to the recalls, they have sullied J&J's reputation, pressured its share price and sparked Congressional investigations.
(Reporting by Lewis Krauskopf; editing by Andre Grenon)
http://news.yahoo.com/s/nm/20110329/hl_nm/us_johnsonandjohnson
Insulin Delivery System Recalled by Roche
Insulin Delivery System Recalled by Roche
TUESDAY, March 29 (HealthDay News) --
ACCU-CHEK FlexLink Plus infusion sets are being recalled by their manufacturer, Roche, because the tube used for inserting the set may become kinked or bent, which could result in the under-delivery or no delivery of insulin, the U.S. Food and Drug Administration has announced.
Inadequate insulin can result in hyperglycemia, which can in turn result in serious complications such as diabetic ketoacidosis and death. Symptoms of hyperglycemia include nausea and vomiting, blurred vision, excessive thirst and/or hunger, fatigue, headache, abdominal pain, frequent urination, and fruity acetone breath. Anyone experiencing these symptoms should check their blood glucose level and consult their health care provider, according to Roche.
Roche has requested that customers refrain from using the ACCU-CHEK FlexLink Plus infusion sets and return unused products. The recall applies only to the ACCU-CHEK FlexLink Plus infusion sets that were launched in November 2010, and not to other infusion sets, such as ACCU-CHEK Ultraflex or other Accu-Chek infusion sets or insulin pumps.
According to the FDA, "patients are to contact their health care providers or caregivers to determine if changes to their therapy are needed and how to temporarily continue insulin pump therapy without the ACCU-CHEK FlexLink Plus infusion set."
More Information TUESDAY, March 29 (HealthDay News) -- ACCU-CHEK FlexLink Plus infusion sets are being recalled by their manufacturer, Roche, because the tube used for inserting the set may become kinked or bent, which could result in the under-delivery or no delivery of insulin, the U.S. Food and Drug Administration has announced.
Inadequate insulin can result in hyperglycemia, which can in turn result in serious complications such as diabetic ketoacidosis and death. Symptoms of hyperglycemia include nausea and vomiting, blurred vision, excessive thirst and/or hunger, fatigue, headache, abdominal pain, frequent urination, and fruity acetone breath. Anyone experiencing these symptoms should check their blood glucose level and consult their health care provider, according to Roche.
Roche has requested that customers refrain from using the ACCU-CHEK FlexLink Plus infusion sets and return unused products. The recall applies only to the ACCU-CHEK FlexLink Plus infusion sets that were launched in November 2010, and not to other infusion sets, such as ACCU-CHEK Ultraflex or other Accu-Chek infusion sets or insulin pumps.
According to the FDA, "patients are to contact their health care providers or caregivers to determine if changes to their therapy are needed and how to temporarily continue insulin pump therapy without the ACCU-CHEK FlexLink Plus infusion set."
More Information
Copyright © 2011 HealthDay. All rights reserved
TUESDAY, March 29 (HealthDay News) --
ACCU-CHEK FlexLink Plus infusion sets are being recalled by their manufacturer, Roche, because the tube used for inserting the set may become kinked or bent, which could result in the under-delivery or no delivery of insulin, the U.S. Food and Drug Administration has announced.
Inadequate insulin can result in hyperglycemia, which can in turn result in serious complications such as diabetic ketoacidosis and death. Symptoms of hyperglycemia include nausea and vomiting, blurred vision, excessive thirst and/or hunger, fatigue, headache, abdominal pain, frequent urination, and fruity acetone breath. Anyone experiencing these symptoms should check their blood glucose level and consult their health care provider, according to Roche.
Roche has requested that customers refrain from using the ACCU-CHEK FlexLink Plus infusion sets and return unused products. The recall applies only to the ACCU-CHEK FlexLink Plus infusion sets that were launched in November 2010, and not to other infusion sets, such as ACCU-CHEK Ultraflex or other Accu-Chek infusion sets or insulin pumps.
According to the FDA, "patients are to contact their health care providers or caregivers to determine if changes to their therapy are needed and how to temporarily continue insulin pump therapy without the ACCU-CHEK FlexLink Plus infusion set."
More Information TUESDAY, March 29 (HealthDay News) -- ACCU-CHEK FlexLink Plus infusion sets are being recalled by their manufacturer, Roche, because the tube used for inserting the set may become kinked or bent, which could result in the under-delivery or no delivery of insulin, the U.S. Food and Drug Administration has announced.
Inadequate insulin can result in hyperglycemia, which can in turn result in serious complications such as diabetic ketoacidosis and death. Symptoms of hyperglycemia include nausea and vomiting, blurred vision, excessive thirst and/or hunger, fatigue, headache, abdominal pain, frequent urination, and fruity acetone breath. Anyone experiencing these symptoms should check their blood glucose level and consult their health care provider, according to Roche.
Roche has requested that customers refrain from using the ACCU-CHEK FlexLink Plus infusion sets and return unused products. The recall applies only to the ACCU-CHEK FlexLink Plus infusion sets that were launched in November 2010, and not to other infusion sets, such as ACCU-CHEK Ultraflex or other Accu-Chek infusion sets or insulin pumps.
According to the FDA, "patients are to contact their health care providers or caregivers to determine if changes to their therapy are needed and how to temporarily continue insulin pump therapy without the ACCU-CHEK FlexLink Plus infusion set."
More Information
Copyright © 2011 HealthDay. All rights reserved
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