Treating patients with hepatitis C who inject illegal drugs using only medication is ineffective without also addressing the complex social issues they face, finds a new study from the University of Victoria.
Although new hepatitis C drugs can cure the liver-wasting disease in most patients, new research suggests the treatment does little to help patients who inject drugs, some of society’s most vulnerable citizens who are also the most challenging to help.
“There’s quite a bit of attention to medical advances (in hepatitis C treatment), but it doesn’t really impact the people most affected (by hepatitis C),” said Bruce Wallace, co-author of the study and an assistant professor at UVic’s School of Social Work. “People are being excluded from access to treatment and it is the people who need it the most.
Read more....
Showing posts with label Treatment. Show all posts
Showing posts with label Treatment. Show all posts
Tuesday, November 3, 2015
Advocates work on stigma, treatment of hepatitis C
Like many hepatitis C patients, Anthony Lo Russo, 64, lived with the virus for years before he knew he had it. Even after a routine blood test flagged it in 1995, he eschewed hep C drugs because of their side effects. “I felt fine, so I waited,” Lo Russo said.
After the 2013 introduction of kinder drugs, Lo Russo agreed to a standard 16-week treatment. Two weeks into it, he heard the word that’s music to hep C patients’ ears; his blood was “clear” of hep C. He was cured.
“I’m happy to be alive,” said Lo Russo, of Lake Worth, Fla. He bowls in three leagues, swims and chats with fellow patients on Facebook.
Read more....
After the 2013 introduction of kinder drugs, Lo Russo agreed to a standard 16-week treatment. Two weeks into it, he heard the word that’s music to hep C patients’ ears; his blood was “clear” of hep C. He was cured.
“I’m happy to be alive,” said Lo Russo, of Lake Worth, Fla. He bowls in three leagues, swims and chats with fellow patients on Facebook.
Read more....
Friday, October 16, 2015
Medicare spending for hepatitis C cures surges
Medicare’s prescription drug program spent nearly $4.6 billion in the first half of this year on expensive new cures for the liver disease hepatitis C — almost as much as it paid for all of 2014.
Rebates from pharmaceutical companies — the amounts of which are confidential — will reduce Medicare’s final tab for the drugs, by up to half. Even so, the program’s spending will likely continue to rise, in part because of strong demand.
Medicare’s stunning outlays, spelled out in data requested from the government by ProPublica, raise troubling questions about how the taxpayer-funded program can afford not only these pricey medications but a slew of others coming on the market
READ MORE....
Rebates from pharmaceutical companies — the amounts of which are confidential — will reduce Medicare’s final tab for the drugs, by up to half. Even so, the program’s spending will likely continue to rise, in part because of strong demand.
Medicare’s stunning outlays, spelled out in data requested from the government by ProPublica, raise troubling questions about how the taxpayer-funded program can afford not only these pricey medications but a slew of others coming on the market
READ MORE....
Friday, October 9, 2015
What the Heck are RAVs? —Alan Franciscus, Editor-in-Chief
RAVs are resistance associated variants. RAVs occur during (viral breakthrough) and after treatment (relapse) with direct acting antiviral medications (inhibitors—protease, polymerase, NS5A). In other words, someone is treated and not cured.
This can lead to a particular class of drugs (protease, polymerase, NS5A inhibitors) not working as well because a person has developed drug resistance.
In clinical trials of the direct acting antiviral medications, approximately 1% to 7% of the trial participants were not cured. In real world settings it is likely higher because of many issues such as missed doses, LIFE, and various health and other issues not addressed in clinical trials.
In this month’s Snapshots, I wrote about a couple of studies that addressed re-treatment. To overcome the RAVs and other negative predictors of treatment response (previous treatment non-response, cirrhosis, etc.,) ribavirin was added to both re-treatment groups. As a result, 75%-100% of the patients were cured. There are drugs being developed that have a high barrier to resistance that will replace ribavirin. Thankfully we have ribavirin now to help people in need of re-treatment and cure and, importantly, to prevent further hepatitis C disease progression.
The approach to retreatment of RAVs is rapidly evolving. Some physicians are beginning to test for RAVs, but it is far from being a routine test. Talk with your medical provider if you have questions.
If you are being re-treated with a direct acting antiviral medication, it is important to find an expert to consult with about the best HCV treatment regime for you.
This can lead to a particular class of drugs (protease, polymerase, NS5A inhibitors) not working as well because a person has developed drug resistance.
In clinical trials of the direct acting antiviral medications, approximately 1% to 7% of the trial participants were not cured. In real world settings it is likely higher because of many issues such as missed doses, LIFE, and various health and other issues not addressed in clinical trials.
In this month’s Snapshots, I wrote about a couple of studies that addressed re-treatment. To overcome the RAVs and other negative predictors of treatment response (previous treatment non-response, cirrhosis, etc.,) ribavirin was added to both re-treatment groups. As a result, 75%-100% of the patients were cured. There are drugs being developed that have a high barrier to resistance that will replace ribavirin. Thankfully we have ribavirin now to help people in need of re-treatment and cure and, importantly, to prevent further hepatitis C disease progression.
The approach to retreatment of RAVs is rapidly evolving. Some physicians are beginning to test for RAVs, but it is far from being a routine test. Talk with your medical provider if you have questions.
If you are being re-treated with a direct acting antiviral medication, it is important to find an expert to consult with about the best HCV treatment regime for you.
Tuesday, October 6, 2015
Health plan tiers raise drug costs for hepatitis patients
This is important information to think about if you have open enrollment. Jacques Chambers article "Open Enrollment" will be featured in the next issue of the October Mid-Monthly HCV Advocate Newsletter - Alan
By Bob Herman | October 5, 2015
A new report says that health insurance companies discriminate against people with hepatitis B and C by charging high out-of-pocket costs for drugs, but the industry lobby has called the analysis “very one-sided” and limited in scope.
The Affordable Care Act prohibits health insurers from discriminating against people on the basis of age, gender or health conditions, and the federal government has already made it clear it will monitor health plans sold on the public exchanges to ensure they meet ACA standards.
The not-for-profit AIDS Institute examined silver-level health plans that were sold on Florida's insurance marketplace in 2015. The group found that eight of the 12 insurers that sold 2015 plans had what it deemed as discriminatory practices for hepatitis B and C drugs. For example, Aetna placed many of its hepatitis drugs on the most expensive tiers with coinsurance rates up to 50%. Humana had a $1,500 prescription drug deductible and also had many of its hepatitis drugs on the highest tiers with large cost-sharing, the report found.
Read more....
By Bob Herman | October 5, 2015
A new report says that health insurance companies discriminate against people with hepatitis B and C by charging high out-of-pocket costs for drugs, but the industry lobby has called the analysis “very one-sided” and limited in scope.
The Affordable Care Act prohibits health insurers from discriminating against people on the basis of age, gender or health conditions, and the federal government has already made it clear it will monitor health plans sold on the public exchanges to ensure they meet ACA standards.
The not-for-profit AIDS Institute examined silver-level health plans that were sold on Florida's insurance marketplace in 2015. The group found that eight of the 12 insurers that sold 2015 plans had what it deemed as discriminatory practices for hepatitis B and C drugs. For example, Aetna placed many of its hepatitis drugs on the most expensive tiers with coinsurance rates up to 50%. Humana had a $1,500 prescription drug deductible and also had many of its hepatitis drugs on the highest tiers with large cost-sharing, the report found.
Read more....
Monday, October 5, 2015
NYU Researchers Find Development of Serious Liver Damage in Mid- to Late-adulthood Among People Who Inject Drugs with Untreated Chronic Hepatitis C Infection
October 5, 2015
N-56 2015-16
Few people who inject drugs are engaged in needed care for chronic HCV infection; Early engagement in treatment needs to be a policy priority for these individuals
The Hepatitis C virus (HCV) infection is a chronic blood-borne viral infection that affects an estimated 160 million people, or 2-3% of the population world-wide. Alarmingly, chronic HCV infection accounts for one-quarter of the cases of cirrhosis and hepatocellular carcinoma (HCC). If HCV is left untreated, chronic liver disease will occur in 60–70% of the cases, cirrhosis in 5–20% of the cases, and 1–5% will die from decompensated cirrhosis or HCC.
In most high-income countries, such as the United States, where drug injection is the primary route of HCV transmission, the disease is concentrated among people who inject drugs (PWID). While it is estimated that 50–80% of PWID are chronically infected, fewer than 5% of PWID have received treatment.
In a new study, “Hepatitis C virus (HCV) disease progression in people who inject drugs (PWID): A systematic review and meta-analysis,” published in the International Journal of Drug Policy, a team of researchers from New York University’s Center for Drug Use and HIV Research (CDUHR) assessed existing data on the natural history of HCV among PWID. A total of twenty-one studies examined over 8500 PWID, who contributed nearly 120,000 person-years at risk, for the study of four major HCV-related outcomes included in the synthesis.
Read more....
N-56 2015-16
Few people who inject drugs are engaged in needed care for chronic HCV infection; Early engagement in treatment needs to be a policy priority for these individuals
The Hepatitis C virus (HCV) infection is a chronic blood-borne viral infection that affects an estimated 160 million people, or 2-3% of the population world-wide. Alarmingly, chronic HCV infection accounts for one-quarter of the cases of cirrhosis and hepatocellular carcinoma (HCC). If HCV is left untreated, chronic liver disease will occur in 60–70% of the cases, cirrhosis in 5–20% of the cases, and 1–5% will die from decompensated cirrhosis or HCC.
In most high-income countries, such as the United States, where drug injection is the primary route of HCV transmission, the disease is concentrated among people who inject drugs (PWID). While it is estimated that 50–80% of PWID are chronically infected, fewer than 5% of PWID have received treatment.
In a new study, “Hepatitis C virus (HCV) disease progression in people who inject drugs (PWID): A systematic review and meta-analysis,” published in the International Journal of Drug Policy, a team of researchers from New York University’s Center for Drug Use and HIV Research (CDUHR) assessed existing data on the natural history of HCV among PWID. A total of twenty-one studies examined over 8500 PWID, who contributed nearly 120,000 person-years at risk, for the study of four major HCV-related outcomes included in the synthesis.
Read more....
Monday, September 28, 2015
MediaplanetUSA’s “Hepatitis & Liver” campaign
We recently participated in MediaplanetUSA’s “Hepatitis & Liver” campaign where industry professionals and associations came together to draw attention to the importance of liver health, while highlighting hepatitis awareness, testing education, and treatment to erase the stigma and judgments attached to the disease. The campaign was distributed within the centerfold of USA Today on September 23, 2015 and is published on a Mediaplanet original site.
Efficacy and safety of Paritaprevir/r/Ombitasvir/Dasabuvir ±Ribavirin in GT1 HCV infected patients treated in real life settings (AMBER study - interim analysis
Editor's Note: Read our Fact Sheet HCV in Japan: click here:
AbbVie's VIEKIRAX® (ombitasvir/paritaprevir/ritonavir tablets) Receives Approval in Japan for the Treatment of Genotype 1 Chronic Hepatitis C
AbbVie's VIEKIRAX® (ombitasvir/paritaprevir/ritonavir tablets) Receives Approval in Japan for the Treatment of Genotype 1 Chronic Hepatitis C
- New interferon and ribavirin-free treatment option for patients with most common type of hepatitis in Japan, genotype 1 chronic hepatitis C, including those with compensated cirrhosis[1]
- VIEKIRAX consists of a 12-week, two direct-acting antiviral, fixed-dose combination of paritaprevir/ritonavir with ombitasvir, dosed once daily[1]
- Approximately 1.5 to 2 million people are living with hepatitis C in Japan, one of the highest rates of hepatitis C infection in the industrialized world[2],[3]
NORTH CHICAGO, Ill., Sept. 28, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) approved VIEKIRAX® (ombitasvir/paritaprevir/ritonavir), as a new interferon and ribavirin-free treatment option for adult patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection, including those with compensated liver cirrhosis.1 VIEKIRAX consists of a 12-week, two direct-acting antiviral, fixed-dose combination of paritaprevir/ritonavir with ombitasvir, dosed once daily.
"Today's approval represents an important step forward for the treatment of Japanese patients, a population with specific needs based on patient and viral characteristics," said Jean-Michel Pawlotsky, MD, PhD, professor of medicine at the University of Paris-Est, France. "VIEKIRAX is a valuable new addition to a number of treatments that are changing the face of hepatitis C, making it possible to achieve high virologic cure rates, even in patients whose disease has progressed to compensated liver cirrhosis."
Japan has one of the highest rates of hepatitis C infection in the industrialized world, with approximately 1.5 to 2 million people living with HCV.2, 3 Genotype 1 is the most common HCV genotype in Japan with 60 to 70 percent of patients infected and, of those, about 95 percent are infected with the genotype 1b (GT1b) sub-type.4
"We are pleased to provide VIEKIRAX as a new treatment that offers a high probability of virologic cure for GT1b HCV patients and are working to support access to our treatment in Japan," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "We are also prioritizing disease education and awareness by collaborating with stakeholders to identify and address the diverse challenges across Japan, such as supporting screening and diagnosis initiatives, and providing accurate information to the medical community about treatment options."
The approval is supported by the Phase 3 GIFT-I study.1 An overall 95 percent (n=140/148) of treatment-naïve and 94 percent (n=102/109) of treatment-experienced GT1b HCV infected patients achieved SVR12 with VIEKIRAX.1
The primary endpoint was achieved, demonstrating 95 percent (n=106/112) SVR12 in a sub-group of treatment-naïve, non-cirrhotic, adult GT1b HCV infected Japanese patients who were eligible for therapy with interferon (IFN) and had a high viral load. A secondary endpoint in GT1b HCV patients with compensated cirrhosis achieved 91 percent (n=38/42) SVR12.5
Across all treatment arms three patients (n=3/363) experienced on-treatment virologic failure, eight patients (n=8/354) experienced post-treatment relapse and three patients discontinued treatment due to adverse events. The most commonly reported adverse events (>5 percent in any arm) were nasopharyngitis, headache, peripheral edema, nausea, pyrexia and decreased platelet count.5 In April 2015, AbbVie was granted priority review by the MHLW for VIEKIRAX, on the basis of clinical usefulness of the treatment and recognizing the severity and unmet need of the disease in Japan.
About the GIFT-I Study5
GIFT-I comprises 363 patients in two sub-studies.
In sub-study 1, 321 genotype 1b (GT1b) patients without cirrhosis, both treatment-naïve and interferon (IFN) [with or without ribavirin (RBV)] treatment-experienced, were randomized to receive either ombitasvir/paritaprevir/ritonavir (Arm A) [OBV/PTV/r] or placebo (Arm B) [2:1 randomization ratio, stratified by treatment history, past response, viral load and IFN eligibility]. Patients initially randomized to placebo (Arm B) then received OBV/PTV/r for an additional 12 weeks of open-label treatment. Sustained virologic response was assessed 12 weeks post-treatment (SVR12) as a primary efficacy endpoint in a sub-group of previously untreated, non-cirrhotic GT1b patients who were eligible for therapy with IFN and had a high viral load, defined as an HCV RNA level ≥ 100,000 IU/mL and received at least one dose of the double-blind, active study drug.
In sub-study 2, 42 GT1b treatment-naïve and IFN (with or without RBV) treatment-experienced patients with compensated cirrhosis received open-label treatment for 12 weeks (Arm C) with SVR12 and assessed as a secondary efficacy endpoint.
One patient from each arm (n=3/363) experienced on-treatment virologic failure [Arm A, 0.5% (n=1/215); Arm B, 0.9% (n=1/106); Arm C, 2.4% (n=1/42)]. Across all arms, eight patients (n=8/354) experienced post-treatment relapse [Arm A, 2.4% (n=5/209); Arm B, 1.0% (n=1/105); Arm C, 5.0% (n=2/40)].
AbbVie studied its two direct-acting antiviral treatment regimen without RBV in Japan due to patient and viral characteristics specific to the Japanese population, including high prevalence of GT1b.
About VIEKIRAX in Japan
Indication in Japan
VIEKIRAX is indicated for the improvement of viremia in chronic hepatitis C or compensated hepatic cirrhosis C in patients of serogroup 1 (genotype 1).
Summary of Safety Information
Contraindications
VIEKIRAX is contraindicated in patients with a history of known hypersensitivity to an ingredient in VIEKIRAX, patients with severe hepatic impairment (Child-Pugh C) or patients being treated with the following drugs: azelnidipine, triazolam, iv midazolam, blonanserin, pimozide, ergotamine tartrate, dihydroergotamine mesilate, ergometrine maleate, methylergometrine maleate, sildenafil citrate [Revatio], tadalafil [Adcirca], rivaroxaban, vardenafil hydrochloride hydrate, riociguat, simvastatin, atorvastatin calcium hydrate, carbamazepine, phenytoin, phenobarbital, rifampin, efavirenz, foods containing St. John's Wort (Hypericum perforatum), ethinyl estradiol-containing medicinal products.
Precautions for Use
Positive result for HCV RNA should be confirmed before administering VIEKIRAX and decompensated cirrhosis should be excluded.
When VIEKIRAX is used for patients co-infected with HIV/HCV, administer VIEKIRAX only to patients whose virological suppression has been achieved by anti-HIV therapy as ritonavir may cause resistance against a HIV protease inhibitor.
During the administration of VIEKIRAX, perform liver function tests regularly because hepatic function disorder may occur.
Co-administration of VIEKIRAX with drugs that are substrates of CYP3A4, P-gp, BCRP, OATP1B1 or OATP1B3 may result in increased plasma concentrations of such drugs, potentially requiring dose adjustment or clinical monitoring.
The safety of VIEKIRAX in pregnant women has not been established. VIEKIRAX should be used in pregnant women and women who may possibly be pregnant only if the expected therapeutic benefits outweigh the possible risks associated with treatment.
Do not administer VIEKIRAX to nursing mothers. If VIEKIRAX is administered to a nursing mother by necessity, breast feeding must be discontinued during treatment.
Safety and effectiveness have not been established in children.
Adverse Reactions
Major adverse reactions included peripheral edema in 15 subjects (4.1%), headache in 12 subjects (3.3%) and nausea in 10 subjects (2.8%)
About AbbVie's HCV Clinical Development Program in Japan
AbbVie's HCV clinical development program in Japan focuses on our two direct-acting antiviral treatment and is designed with the goal of achieving high SVR rates in chronic HCV infected patients, including additional genotypes and patients with compensated cirrhosis.
Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. Paritaprevir has been developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of hepatitis C.
About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.
Forward-Looking Statements
Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.
Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2014 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.
1 VIEKIRAX [package insert]. Tokyo, Japan: AbbVie Ltd; 2015.
2 Kohnodai Hospital. National Center for Global Health and Medicine [cited 20 February 2013]. Available from: http://www.ncgm.go.jp/center/forpatient_hcv.html
3 Gower, E. Global epidemiology and genotype distribution of the hepatitis C virus infection. Journal of Hepatology 2014; 61: S45-S57, Table 2.
4 Hajarizadeh B et al. Nat Rev Gastroenterol Hepatol 2013; 10: 553-562. Available from: http://www.nature.com/nrgastro/journal/v10/n9/fig_tab/nrgastro.2013.107_F1.html
5 Kumada H, et al. Randomized phase 3 trial of ombitasvir/paritaprevir/ritonavir for hepatitis C virus genotype 1b-infected Japanese patients with or without cirrhosis. Hepatology. 2015 Jul 3. doi: 10.1002/hep.27972.
SOURCE AbbVie
For further information: Media: Judy Low, +65 9880 2604, judy.low@abbvie.com; or Jane Woo, +1 (847) 937-4754, jane.woo@abbvie.com; or Investor Relations: Liz Shea, +1 (847) 935-2211, liz.shea@abbvie.com
Thursday, September 17, 2015
Managing Hepatitis C: Advances in treatment & evaluation
Improvements to the efficacy and side effects of hepatitis C medications have simplified the disease management calculus, tipping the scales towards treatment.
The availability of effective oral medication has also raised the bar for clinicians: is there a way to make similar progress in the evaluation side? What would it take to stage the disease quickly, safely, and without discomfort for the patient?
The stiffness of the patient's liver tissue, categorized at a certain stiffness as "fibrosis," provides hepatologists important diagnostic information about the extent and stage of hepatitis C. Liver biopsy has long been the gold standard for obtaining this information. However, biopsies are time-consuming invasive procedures that routinely cause patients pain and, in some rare instances, lead to greater complications such as internal bleeding. These procedures take up clinical staff time, necessitate bed space, and incur instrument and room sterilization costs. Lastly, they are subject to not insignificant sampling limitations, as each biopsy takes only a small sample from a large organ.
Read more...
The availability of effective oral medication has also raised the bar for clinicians: is there a way to make similar progress in the evaluation side? What would it take to stage the disease quickly, safely, and without discomfort for the patient?
The stiffness of the patient's liver tissue, categorized at a certain stiffness as "fibrosis," provides hepatologists important diagnostic information about the extent and stage of hepatitis C. Liver biopsy has long been the gold standard for obtaining this information. However, biopsies are time-consuming invasive procedures that routinely cause patients pain and, in some rare instances, lead to greater complications such as internal bleeding. These procedures take up clinical staff time, necessitate bed space, and incur instrument and room sterilization costs. Lastly, they are subject to not insignificant sampling limitations, as each biopsy takes only a small sample from a large organ.
Read more...
Achillion Reports 100% SVR12 From Second Cohort of Patients in the Previously-Completed Six Week Phase 2 Trial Evaluating Odalasvir (ACH-3102) and Sofosbuvir for Genotype 1 HCV ("Proxy Study")
- 100% SVR12 reported for all patients treated for six- (n=18) or eight-weeks (n=12) —
- Odalasvir (ACH-3102) is the subject of an exclusive, worldwide development and commercialization license granted to Janssen -
NEW HAVEN, Conn., Sept. 17, 2015 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced additional interim results from a Phase 2 study evaluating odalasvir (also known as ACH-3102), a NS5A inhibitor, in combination with sofosbuvir, without ribavirin, for either six or eight weeks of treatment in patients with treatment-naïve genotype 1 chronic hepatitis C virus (HCV) infection. Of the patients treated for six weeks in this cross-over cohort, 100 percent (n=6/6) remained HCV RNA undetectable twelve weeks after completing therapy (SVR12). Previously, Achillion reported results from this study including 100 percent SVR24 for the initial cohorts including 12 patients treated for eight weeks and 100 percent SVR24 for 12 patients treated for six weeks.
In May 2015, Achillion announced it had granted Janssen Pharmaceuticals, Inc. (Janssen), one of the Janssen Pharmaceutical Companies of Johnson & Johnson, an exclusive, worldwide license to develop and, upon regulatory approval, commercialize HCV products and regimens containing one or more of Achillion's HCV assets which include odalasvir, ACH-3422, and sovaprevir.
ACH-3102 - 017: Phase 2 pilot study evaluating six- and eight-weeks of treatment in combination with sofosbuvir for genotype 1 treatment-naïve HCV
Achillion conducted a Phase 2, open-label, randomized, partial-crossover study to evaluate the efficacy, safety, and tolerability of eight weeks or six weeks of odalasvir and sofosbuvir, a marketed nucleotide polymerase inhibitor, without ribavirin, in treatment-naïve genotype 1 HCV-infected patients. The primary objective of the study was determination of sustained viral response 12 weeks (SVR12) after the completion of therapy. Eighteen patients were initially enrolled, including six observational patients (group 1). Twelve patients completed eight weeks of treatment consisting of 50 mg of odalasvir and 400 mg of sofosbuvir administered once daily while observational patients received no drug during this phase of the trial. Ten of the 12 patients receiving eight weeks of treatment had genotype 1a HCV. At baseline, the median HCV RNA was 7.15 log10 (range 5.5 — 7.8 log10). Of the 12 patients, 100 percent achieved SVR24. Odalasvir and sofosbuvir were well tolerated with no significant adverse events, ECG findings, or lab abnormalities observed during treatment.
Following achievement of the pre-specified response rate of 100 percent, the six observational patients plus six additional patients (group 2) were enrolled and received six weeks of treatment consisting of 50 mg of odalasvir and 400 mg of sofosbuvir administered once daily. Median HCV RNA at baseline was 6.95 log10 (range 6.2 — 8.0 log10) and six patients had GT 1a HCV. Of the 12 patients, 100 percent achieved SVR24.
Six additional rollover patients (group 3), enrolled into the final cohort, also received six weeks of treatment consisting of 50 mg of odalasvir and 400 mg of sofosbuvir administered once daily. Baseline characteristics included five of six patients with genotype 1a HCV, four of six patients with non-CC IL28B (two patients with IL28B TT), and a median baseline HCV RNA of 6.32 log10 IU/ml (range 6.0 — 7.3 log10 IU/ml). In all, a total of 18 patients (group 2 and 3) received six weeks of treatment and all subjects, 100 percent, achieved SVR12.
About the Achillion Worldwide HCV Collaboration with Janssen
On May 19, 2015, Achillion announced it had granted Janssen Pharmaceuticals, Inc. (Janssen), one of the Janssen Pharmaceutical Companies of Johnson & Johnson, an exclusive, worldwide license to develop and, upon regulatory approval, commercialize HCV products and regimens containing one or more of Achillion's HCV assets which include odalasvir (ACH-3102), ACH-3422, and sovaprevir. A key objective of the collaboration is to develop a short-duration, highly effective, pan-genotypic, oral regimen for the treatment of HCV. Achillion announced on August 3, 2015 that Alios Biopharma Inc., part of the Janssen Pharmaceutical Companies (Janssen) had initiated a Phase 1 clinical trial to evaluate the potential effect of simeprevir and odalasvir on the pharmacokinetics of AL-335 in healthy volunteers. Janssen previously stated its goal of initiating Phase 3 development with a triple regimen for HCV by early 2017.
About HCV
The hepatitis C virus (HCV) is one of the most common causes of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 150 million people are infected with HCV worldwide including more than 5 million people in the United States. Three-quarters of the HCV patient population is undiagnosed; it is a silent epidemic and a major global health threat. Chronic hepatitis, if left untreated, can lead to permanent liver damage that can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection.
About Achillion Pharmaceuticals
Achillion is seeking to apply its expertise in biology and structure-guided design and a deep understanding of patient and clinician needs to develop innovative treatment solutions aimed at improving patients' lives. Achillion believes that its scientific excellence, integrated capabilities and experienced team position it to successfully achieve its goal of advancing new products along the entire continuum from the bench to the patient. Achillion's pipeline is currently focused on small molecule therapeutics for infectious disease and complement-related diseases. www.achillion.com
Cautionary Note Regarding Forward-Looking Statements
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors that could cause actual results to differ materially from those indicated by such forward-looking statements. Achillion may use words such as "expect," "anticipate," "project," "intend," "plan," "aim," "believe," "seek," " estimate," "can," "focus," "will," and "may" and similar expressions to identify such forward-looking statements. Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: comply with its obligations under and otherwise maintain its collaboration agreement with Janssen on the agreed upon terms; demonstrate, either alone or through its collaborators, the requisite safety, efficacy and combinability of its drug candidates, and advance the preclinical and clinical development of its drug candidates under the timelines it projects in current and future clinical trials; obtain and maintain necessary regulatory approvals; obtain and maintain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete effectively and successfully; manage expenses; manage litigation; raise the substantial additional capital needed to achieve its business objectives; and successfully execute on its business strategies. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2014, its quarterly report on Form 10-Q for the quarter ended June 30, 2015, and its subsequent SEC filings.
In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any duty to update any forward-looking statement, except as required by applicable law.
Company Contact:
Glenn Schulman
Achillion Pharmaceuticals, Inc.
Tel. (203) 624-7000
gschulman@achillion.com
Investors:
Mary Kay Fenton
Achillion Pharmaceuticals, Inc.
Tel. (203) 624-7000
mfenton@achillion.com
Investors:
Tricia Truehart
The Trout Group, LLC
Tel. (646) 378-2953
ttruehart@troutgroup.com
Tuesday, September 15, 2015
Hepatitis C in Children
—Alan Franciscus, Editor-in-Chief
It is estimated that Hepatitis C (HCV) occurs in about 0.15% of 6-11 year-olds and 0.4% of 12-19 year-olds. It is estimated that there are 23,000 to 46,000 children in the US with HCV.1 The actual number of children with HCV is unknown because children are not routinely tested for it.
Prior to 1992, the most common transmission route for HCV in children was through blood transfusion, blood products, and organ transplantation. Now that blood products and organs are screened for hepatitis C the most frequent transmission of hepatitis C in infants is mother-to-child transmission. The second most common transmission route in children and teenagers is in those who share equipment to inject drugs (needles, cookers, cotton, water, etc.)
Transmission of HCV from an HCV-infected mother-to-infant occurs about 6% of the time. It can occur up to 10% of the time if a mother is coinfected with HIV and hepatitis C. Also, a high viral load increases the risk of mother-to-infant transmission. Unfortunately, there are no effective strategies or drugs to prevent the transmission of HCV from mother to child.
When a baby is born to an HCV-infected mother, the child will acquire the mother’s HCV antibodies. For this reason, the child will not be tested for HCV antibodies for 18 months. This is the period that it takes for the baby’s body to clear out the mother’s antibodies.
An HCV RNA or viral load test can be given as early as one month. It might be too early since the HCV RNA, or viral load fluctuates during the acute infection phase. Also, babies have a high rate of natural clearance. Most medical providers prefer to wait out the 18-month period to test for HCV antibodies and the confirmatory HCV RNA (viral load test).
Table 1. Children for whom screening is recommended.
Diagnosis and management of hepatitis C infection in infants, children, and adolescents Pediatric Gastroenterol, Nutr 2012;54:838-855
Baker R. Viral Hepatitis. In: Pohl JF, editor. Pediatric Gastroenterology. Baton Rougue, FL: CRC Press: 2014. pp 313-327
*I read this recommendation with interest because we know that receiving a tattoo or piercing in a commercial parlor is safe. .
Chronic Infection
Approximately 75% of infants who are acutely infected with hepatitis C will continue to chronic infection. In children, the rate of disease progression is slow. There is, however, a small percentage (estimated at less than 2%) of children in whom there is a rapid rate of disease progression that could lead to fibrosis and cirrhosis.
Watch, Wait and Protect
A baby born to an HCV-infected mother should receive the hepatitis A and hepatitis B vaccines to protect the child from becoming infected with another liver disease. As well the baby and child should receive other immunizations to protect the health of the child.
Hepatitis C is not spread by casual contact and infected children should not be restricted from attending daycare or school. Children should be taught that they should not share toothbrushes, nail clippers, razors or any other items that have the potential to transmit hepatitis C.
Any drug, herb or supplement that the child is given should be screened to make sure that it is liver safe. When the child is older, a discussion should take place about sex, drugs, and alcohol.
Most importantly, a child should be medically monitored on a regular basis.
When to Tell a Child
Telling a child that they have hepatitis C can be one of the most difficult decisions a parent can ever make. The timing is the most important decision. The best advice is never to lie to a child. We have an excellent fact sheet that can provide plenty of advice to parents. http://hcvadvocate.org/hepatitis/factsheets_pdf/TellChild_HCV.pdf
Treatment
As stated above most children have a slowly progressive disease. For the small percentage that have severe fibrosis or cirrhosis, immediate treatment may be needed. The decision to treat or not is never easy and in children it is even more difficult. Some questions that are important to consider include:
Current treatment of pegylated interferon plus ribavirin is approved for children who are three years and older with compensated cirrhosis.
Again, most children have slowly progressive disease, and it takes decades before serious liver disease develops. By this time, children will age to adults and be eligible for interferon- and ribavirin-free therapies that approach 100% effectiveness.
The Future
Hepatitis C infections are on the rise. The so-called Second Epidemic of hepatitis C is affecting females equally as males. As a result, there will be many women of child-bearing age that will become pregnant and have children who may also have hepatitis C.
For the first time, there is an opportunity to prevent mother-to-child transmission. Direct-acting antiviral medications without ribavirin that are pregnancy category B.
Pregnancy Category B: In humans, there are no well-controlled studies. However, in animal studies, pregnant animals received the medicine, and the babies did not show any problems related to the medicine.
However, there have not been any clinical studies using the interferon- and ribavirin-free medications in pregnant women. As a result, studies are needed to evaluate the safety and effectiveness of these new drugs for the mother and the infant.
1American Liver Foundation
Source: Hepatitis C in Children in Times of Changes, Robert D. Baker and Susan S. Baker Walters Kluwer Health, Inc.
It is estimated that Hepatitis C (HCV) occurs in about 0.15% of 6-11 year-olds and 0.4% of 12-19 year-olds. It is estimated that there are 23,000 to 46,000 children in the US with HCV.1 The actual number of children with HCV is unknown because children are not routinely tested for it.
Prior to 1992, the most common transmission route for HCV in children was through blood transfusion, blood products, and organ transplantation. Now that blood products and organs are screened for hepatitis C the most frequent transmission of hepatitis C in infants is mother-to-child transmission. The second most common transmission route in children and teenagers is in those who share equipment to inject drugs (needles, cookers, cotton, water, etc.)
Transmission of HCV from an HCV-infected mother-to-infant occurs about 6% of the time. It can occur up to 10% of the time if a mother is coinfected with HIV and hepatitis C. Also, a high viral load increases the risk of mother-to-infant transmission. Unfortunately, there are no effective strategies or drugs to prevent the transmission of HCV from mother to child.
When a baby is born to an HCV-infected mother, the child will acquire the mother’s HCV antibodies. For this reason, the child will not be tested for HCV antibodies for 18 months. This is the period that it takes for the baby’s body to clear out the mother’s antibodies.
An HCV RNA or viral load test can be given as early as one month. It might be too early since the HCV RNA, or viral load fluctuates during the acute infection phase. Also, babies have a high rate of natural clearance. Most medical providers prefer to wait out the 18-month period to test for HCV antibodies and the confirmatory HCV RNA (viral load test).
Table 1. Children for whom screening is recommended.
- Children and adolescents with unexplained elevated aminotransferasesChildren at risk for vertically acquired HCV
- Children from regions with high prevalence of HCV (adoptees, refugees, immigrants)
- Children and adolescents with HIV
- Children or adolescents who are victims of sexual assault
- Adolescents with multiple sexual partners
- Adolescents who are or were intravenous drug users, even if only once in the past
- Children or adolescents who have ever been on dialysis
- Sexual partner of HCV-infected person
- Children or adolescent who have received needle stick (needles, piercing or tattooing)*
Diagnosis and management of hepatitis C infection in infants, children, and adolescents Pediatric Gastroenterol, Nutr 2012;54:838-855
Baker R. Viral Hepatitis. In: Pohl JF, editor. Pediatric Gastroenterology. Baton Rougue, FL: CRC Press: 2014. pp 313-327
*I read this recommendation with interest because we know that receiving a tattoo or piercing in a commercial parlor is safe. .
Chronic Infection
Approximately 75% of infants who are acutely infected with hepatitis C will continue to chronic infection. In children, the rate of disease progression is slow. There is, however, a small percentage (estimated at less than 2%) of children in whom there is a rapid rate of disease progression that could lead to fibrosis and cirrhosis.
Watch, Wait and Protect
A baby born to an HCV-infected mother should receive the hepatitis A and hepatitis B vaccines to protect the child from becoming infected with another liver disease. As well the baby and child should receive other immunizations to protect the health of the child.
Hepatitis C is not spread by casual contact and infected children should not be restricted from attending daycare or school. Children should be taught that they should not share toothbrushes, nail clippers, razors or any other items that have the potential to transmit hepatitis C.
Any drug, herb or supplement that the child is given should be screened to make sure that it is liver safe. When the child is older, a discussion should take place about sex, drugs, and alcohol.
Most importantly, a child should be medically monitored on a regular basis.
When to Tell a Child
Telling a child that they have hepatitis C can be one of the most difficult decisions a parent can ever make. The timing is the most important decision. The best advice is never to lie to a child. We have an excellent fact sheet that can provide plenty of advice to parents. http://hcvadvocate.org/hepatitis/factsheets_pdf/TellChild_HCV.pdf
Treatment
As stated above most children have a slowly progressive disease. For the small percentage that have severe fibrosis or cirrhosis, immediate treatment may be needed. The decision to treat or not is never easy and in children it is even more difficult. Some questions that are important to consider include:
- Can treatment be postponed until the interferon-free therapies are available?
- Is there an interferon-free clinical trial that your child can enroll in?
- Are you and your child ready to take on interferon treatment and the side effects?
- The new medications are very expensive—there is always the possibility that your insurance company may not cover the new medications.
Current treatment of pegylated interferon plus ribavirin is approved for children who are three years and older with compensated cirrhosis.
Again, most children have slowly progressive disease, and it takes decades before serious liver disease develops. By this time, children will age to adults and be eligible for interferon- and ribavirin-free therapies that approach 100% effectiveness.
The Future
Hepatitis C infections are on the rise. The so-called Second Epidemic of hepatitis C is affecting females equally as males. As a result, there will be many women of child-bearing age that will become pregnant and have children who may also have hepatitis C.
For the first time, there is an opportunity to prevent mother-to-child transmission. Direct-acting antiviral medications without ribavirin that are pregnancy category B.
Pregnancy Category B: In humans, there are no well-controlled studies. However, in animal studies, pregnant animals received the medicine, and the babies did not show any problems related to the medicine.
However, there have not been any clinical studies using the interferon- and ribavirin-free medications in pregnant women. As a result, studies are needed to evaluate the safety and effectiveness of these new drugs for the mother and the infant.
1American Liver Foundation
Source: Hepatitis C in Children in Times of Changes, Robert D. Baker and Susan S. Baker Walters Kluwer Health, Inc.
Monday, August 31, 2015
14 million EU citizens living with Hepatitis C; low figures for Malta
There are currently around 13.3 million Europeans living with hepatitis B and 14 million living with hepatitis C, MEP Miriam Dalli pointed out in a question posed to the European Parliament.
“Approximately 120,000 people in Europe every year die because of these diseases.”
In Malta, the number of cases did not seem high in 2013, with 3.3 people per 100,000 being reported as having been infected that year. The number in other states is considerably higher such as in the UK, where the number stood at 21.5 per 100,000 people (nearly 14,000 in total that year).
Read more......
Sunday, June 21, 2015
VA to outsource care for 180,000 vets with hepatitis C
PHOENIX — The Department of Veterans Affairs is moving to outsource care nationwide for up to 180,000 veterans who have hepatitis C, a serious blood and liver condition treated with expensive new drugs that are costing the government billions of dollars.
The VA has spent weeks developing a dramatic and controversial transition as patient loads have surged and funding has run out. Those efforts were not disclosed until records were released this week to The Arizona Republic.
Instructions on how to carry out the program show that the sickest veterans generally will get top priority for treatment. However, patients who have less than a year to live or who suffer "severe irreversible cognitive impairment" will not be eligible for treatment.
Read more...
The VA has spent weeks developing a dramatic and controversial transition as patient loads have surged and funding has run out. Those efforts were not disclosed until records were released this week to The Arizona Republic.
Instructions on how to carry out the program show that the sickest veterans generally will get top priority for treatment. However, patients who have less than a year to live or who suffer "severe irreversible cognitive impairment" will not be eligible for treatment.
Read more...
Wednesday, March 25, 2015
USA-Lack of Insurance Bars Some from Hepatitis C Treatment
Survey data from 2001 to 2010 show that lack of insurance kept some people with hepatitis C virus from getting treatment.
Recently, more effective and well-tolerated drugs have been developed to treat hepatitis C, removing many of the discouraging side effects of older drugs. The infection is curable and transmission can be prevented, researchers write in the American Journal of Gastroenterology.
But for the more than three million people in the U.S. who have chronic liver disease from hepatitis C, there are still two important barriers to getting treatment, said lead author Dr. Ivo Ditah from the Mayo Clinic in Rochester, Minnesota.
Wednesday, March 18, 2015
Zydus, Gilead Sciences, SoviHep, Sofosbuvir, Ledipasvir, HCV, Liver Gilead Sciences And Zydus Launch SoviHep Hepatitis C Drug
American biotechnology firm Gilead Sciences and Indian pharmaceutical company Zydus launched SoviHep, a drug for treating Hepatitis C.On Tuesday, March 17, Zydus issued a statement that confirmed it has signed a non-exclusive agreement with Gilead Sciences, which will enable the company to manufacture sofosbuvir, trade name SoviHep, as well as fixed-dose combination of sofosbuvir/ ledipasvir for circulation in more than 90 countries, which includes India. The drug will be marketed by Zydus Heptiza, which is a specialty division in the group.Hepatitis C may affect the quality of life for patients. Pankaj Patel, Managing Director and Chairman of the Zydus Group, reveals that the launch of SoviHep will provide better treatment for the disease and improve the quality of life for millions of people.Read more...
Thursday, March 12, 2015
Hepatitis C a focus at CROI
New interferon-free treatment can cure nearly 100 percent of HIV-positive people coinfected with hepatitis C virus, researchers reported at the recent 2015 Conference on Retroviruses and Opportunistic Infections in Seattle. But another study showed that delaying treatment results in a higher risk of liver-related complications and death even after being cured.
Two studies presented at the conference showed that HIV/HCV coinfected people can expect the same high cure rates as HIV-negative people using recently or soon-to-be approved antivirals.
Susanna Naggie from Duke Clinical Research Institute presented results from ION-4, a trial evaluating Gilead Science's HCV polymerase inhibitor sofosbuvir and NS5A inhibitor ledipasvir – the drugs in the Harvoni coformulation approved last October. The study enrolled 335 coinfected participants, mostly with HCV genotype 1 (the most common type in the U.S.).
Read more...
Two studies presented at the conference showed that HIV/HCV coinfected people can expect the same high cure rates as HIV-negative people using recently or soon-to-be approved antivirals.
Susanna Naggie from Duke Clinical Research Institute presented results from ION-4, a trial evaluating Gilead Science's HCV polymerase inhibitor sofosbuvir and NS5A inhibitor ledipasvir – the drugs in the Harvoni coformulation approved last October. The study enrolled 335 coinfected participants, mostly with HCV genotype 1 (the most common type in the U.S.).
Read more...
Wednesday, March 11, 2015
Dubai-New oral drug can cure hepatitis C
Dubai: In what is being hailed by health practitioners as one of the biggest discoveries in five decades in the field of medicine, an international pharmaceutical company has discovered a powerful antiviral drug to treat the deadly disease hepatitis C that will soon be available in the UAE.
Experts in the medical field reacted with excitement at this breakthrough development. “We are very excited and thrilled by this discovery which has far-reaching implications,” said a senior doctor from a leading hospital group in Dubai. ”The mechanism by which this oral drug eliminates the virus in the affected population could hold the key to similar anti-viral medication to eliminate many viral diseases such as other forms of hepatitis, Ebola and, one day, even HIV.”
Dr Chacko George, specialist in Internal Medicine at RAK Hospital, said: “In the case of hepatitis C, 20-30 per cent of the people recover and about the same percentage get chronic liver disease or become carriers and even suffer from cancer. If there is an antiviral drug that can eliminate the virus in about 97 per cent of the first-timers and 93 per cent of those treated earlier, then it is one of the greatest breakthroughs in the history of treatment of this disease. This would mean that with this treatment, the infected person will be able to maintain an infection-free state or have such weak copies of the virus which won’t be able to replicate. It would mean a tremendous advancement in the treatment of the disease. It is discoveries like these that keep our medical appetite for discoveries alive.”
Tuesday, February 24, 2015
SVR rates up with new regimens for HCV and HIV coinfection
For patients with hepatitis C virus genotype 1 and HIV coinfection, new regimens are effective and correlate with high rates of sustained virologic response after treatment, according to two studies published online Feb. 23 in the Journal of the American Medical Association.
(HealthDay)—For patients with hepatitis C virus (HCV) genotype 1 and HIV coinfection, new regimens are effective and correlate with high rates of sustained virologic response (SVR) after treatment, according to two studies published online Feb. 23 in the Journal of the American Medical Association.
Mark S. Sulkowski, M.D., from Johns Hopkins University in Baltimore, and colleagues conducted an open-label trial at 17 sites in the United States and Puerto Rico. Sixty-three patients with HCV genotype 1 and HIV-1 coinfection received the all-oral 3 direct-acting antiviral (3D) regimen of ombitasvir, paritaprevir (co-dosed with ritonavir), dasabuvir, and ribavirin for 12 or 24 weeks. The researchers found that 94 and 91 percent, respectively, of those receiving 12 or 24 weeks of 3D and ribavirin achieved SVR at post-treatment week 12 (SVR12). Fatigue, insomnia, nausea, and headache were the most common treatment-emergent adverse events (48, 19, 18, and 16 percent, respectively).
Read more...
(HealthDay)—For patients with hepatitis C virus (HCV) genotype 1 and HIV coinfection, new regimens are effective and correlate with high rates of sustained virologic response (SVR) after treatment, according to two studies published online Feb. 23 in the Journal of the American Medical Association.
Mark S. Sulkowski, M.D., from Johns Hopkins University in Baltimore, and colleagues conducted an open-label trial at 17 sites in the United States and Puerto Rico. Sixty-three patients with HCV genotype 1 and HIV-1 coinfection received the all-oral 3 direct-acting antiviral (3D) regimen of ombitasvir, paritaprevir (co-dosed with ritonavir), dasabuvir, and ribavirin for 12 or 24 weeks. The researchers found that 94 and 91 percent, respectively, of those receiving 12 or 24 weeks of 3D and ribavirin achieved SVR at post-treatment week 12 (SVR12). Fatigue, insomnia, nausea, and headache were the most common treatment-emergent adverse events (48, 19, 18, and 16 percent, respectively).
Read more...
Wednesday, January 28, 2015
New treatments available in Alaska for Hepatitis C
ANCHORAGE –Hepatitis C is a disease that health officials say kills more Alaskans than HIV and AIDS, but according to state health officials, most of the people who have the virus don’t know it.
State Hepatitis prevention coordinator Ginger Provo says more than 16,000 Alaskans have been infected with the Hepatitis C virus since the state started keeping records in the mid 1990s. But Provo believes the real numbers are much higher. She said up to 75 percent of people who have the disease have not been diagnosed because many of them aren’t experiencing symptoms.
The one bright spot for the disease lies in its treatment. New drugs have been released recently that work better, faster and with fewer side effects than previous treatments, Provo says.
Read more...
State Hepatitis prevention coordinator Ginger Provo says more than 16,000 Alaskans have been infected with the Hepatitis C virus since the state started keeping records in the mid 1990s. But Provo believes the real numbers are much higher. She said up to 75 percent of people who have the disease have not been diagnosed because many of them aren’t experiencing symptoms.
The one bright spot for the disease lies in its treatment. New drugs have been released recently that work better, faster and with fewer side effects than previous treatments, Provo says.
Read more...
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