Ribavirin for treating Crimean Congo hemorrhagic fever—latest Cochrane review

In continuation of my update on Ribavirin

In a viral haemorrhagic disease where up to 40% of people developing it die, it is remarkable that doctors still do not agree whether the only recognised treatment, an antiviral drug called ribavirin, makes a difference. In a new Cochrane Review a team of authors at LSTM, along with colleagues in London, The Philippines and in Greece, evaluated the evidence to assess the effectiveness of treating Crimean Congo haemorrhagic fever (CCHF).

Crimean Congo haemorrhagic fever is spread by the bite of an infected tick, and is becoming more common, with outbreaks in Turkey, Eastern Europe and the Eastern Mediterranean. Doctors treat the infection in hospital with intravenous fluids, blood and good nursing care. The debates around ribavirinare common amongst clinicians treating the disease, with strong advocates on one side, and others who have policies not to use it, so the authors hoped the review would settle the debate.

The review authors found just one trial with 136 participants, and some observational comparative studies of 612 participants: overall the analysis did not provide a clear answer. When the authors examined studies that were often quoted as showing benefit, they were critically biased. Although fewer people died in groups receiving ribavirin, the apparent effect could be due to the drug, or equally because those getting the drug may have also been less sick, or received high quality nursing and medical care earlier in the disease.

Lead author, LSTM's Dr. Samuel Johnson, said: "Some doctors advocate giving ribavirin, and state that not to give it is even unethical. The problem is that the studies claiming to demonstrate benefit from the drug are designed in such a way we cannot separate the effect of the drug from other factors, and thus we do not know if ribavirin is effective at all."

The review clarifies the need for reliable research from a randomised control trial to establish whether ribavirin is effective. "The irony is that the strong beliefs and the widespread use of the drug may make it difficult to actually carry out the research needed" states Dr. Johnson. "What we need to know is whether it works, when it works, and how good it is."

But is there any harm in just giving it in case it works? Dr. Johnson points out, "Using unreliable research as evidence of benefit if it doesn't work could potentially waste resources and harm patients, we would also need to investigate other options. On the other hand, if ribavirin does work, then it needs to be rolled out to all patients who could benefit, which is currently not the case."

Whilst research into emerging infectious diseases and during outbreaks is difficult, the team hopes that the reviewprovides an opportunity to strengthen the call for greater steps to be taken to facilitate rigorous research providing reliable results in outbreaks of infectious diseases.

Ref : http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD012713.pub2/abstract;jsessionid=9510BA3ECC4167F7B1CC8995CA6675B1.f03t03

AbbVie Receives U.S. FDA Approval of Once-Daily Viekira XR (dasabuvir, ombitasvir, paritaprevir and ritonavir) for the Treatment of Genotype 1 Chronic Hepatitis C

In continuation of my update on Dasabuvir,  ombitasvir, paritaprevir and ritonavir

 AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has approved a New Drug Application (NDA) for Viekira XR (dasabuvir, ombitasvir, paritaprevir and ritonavir) extended-release tablets. Viekira XR is a once-daily, extended-release co-formulation of the active ingredients in Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) and is for the treatment of patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection, including those with compensated cirrhosis (Child-Pugh A). Viekira XR is not for people with decompensated cirrhosis.

 dasabuvir    ombitasvir

Paritaprevir  ritonavir

Viekira XR is the first co-formulated three direct-acting antiviral (DAA) treatment for adult patients with GT1 HCV. Viekira XR is given once-daily as three oral tablets and must be taken with a meal. It is used without ribavirin (RBV) in GT1b patients and in combination with twice daily RBV in GT1a patients. The approval is supported by Phase 3 clinical trials for Viekira Pak which include data that demonstrated 100 percent sustained virologic response 12 weeks following treatment (SVR12) in GT1b patients with 12 weeks of therapy without ribavirin and 95 percent SVR12 in GT1a patients when used with ribavirin for 12 or 24 weeks of therapy.

"AbbVie's work continues to contribute to the transformation of hepatitis C care through our focus on evolving our current therapies as part of our ongoing commitment to patients," said Rob Scott, M.D., vice president, development and chief medical officer, AbbVie. "The approval of Viekira XR provides a new treatment option for genotype 1 hepatitis C patients in the U.S. with clinical trial data using the components of Viekira XR demonstrating 100 percent cure rates in genotype 1b patients."

There are six major HCV genotypes (GT1-6) and GT1 is the most prevalent form of HCV in the U.S., accounting for approximately 74 percent of all cases.1 Hepatitis C continues to be an important public health issue, with the Centers for Disease Control and Prevention (CDC) estimating that in the U.S. approximately 2.7 million people are chronically infected with HCV.2

The approval of Viekira XR is supported by data from seven Phase 3 clinical trials in more than 2,300 patients who received Viekira Pak with or without RBV for 12 or 24 weeks and two bioavailability studies comparing the formulations.

About Clinical Studies

The components of Viekira XR (administered twice daily with a meal) have been studied in seven Phase 3 clinical trials where 1076 subjects (including 181 with compensated cirrhosis) received the recommended regimen of Viekira +/? RBV for 12 weeks, or for 24 weeks in GT1a patients with compensated cirrhosis. Ninety-five to 100 percent achieved SVR12, which means the hepatitis C virus is not detectable in the blood three months after treatment ends. Cure rates varied by the subtype of hepatitis C and whether or not the person had cirrhosis. Individual results may vary.

USE

Viekira XR (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets/Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) (Viekira) are prescription medicines used with or without ribavirin to treat adults with genotype 1 chronic (lasting a long time) hepatitis C (hep C) virus infection.

Viekira can be used in people who have compensated cirrhosis.

Viekira is not for people with advanced cirrhosis (decompensated). If people have cirrhosis, they should talk to a doctor before taking Viekira.

About Viekira XR

The components of Viekira XR* have been studied in a broad range of genotype 1 (GT1) patients with chronic hepatitis C virus (HCV) infection, ranging from treatment-naïve to difficult to treat patients, such as those with compensated (mild, Child-Pugh A) cirrhosis of the liver, HCV/HIV-1 co-infection, liver transplant recipients with normal hepatic function and mild fibrosis, and those who have failed previous treatment with pegylated interferon (pegIFN) and ribavirin (RBV).

The extended-release co-formulation of these components, Viekira XR, consists of 200 mg of dasabuvir, 8.33 mg of ombitasvir, 50 mg of paritaprevir, and 33.33 mg of ritonavir per tablet, and is dosed three tablets once daily. Viekira XR must be taken with a meal, and tablets should be swallowed whole. People should not drink alcohol within four hours of taking Viekira XR. Viekira XR is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B and C) due to risk of potential toxicity. Viekira XR is taken for 12 weeks, except in GT1a patients with cirrhosis and all liver transplant recipients with normal hepatic function and mild fibrosis, who should take it for 24 weeks. Ribavirin should be co-administered in GT1a patients and in all patients who have received a liver transplant.

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 is used in combination with AbbVie's ombitasvir with or without dasabuvir for the treatment of hepatitis C.

*Given as a fixed-dose combination of ombitasvir 25mg (an NS5A inhibitor), paritaprevir 150mg (an NS3/4A protease inhibitor), and ritonavir 100mg (an HIV-1 protease inhibitor), dosed once daily with a meal, and dasabuvir 250mg (a non-nucleoside NS5B palm polymerase inhibitor), dosed twice daily with a meal.

Investigational antiviral drug effectively treats Lassa virus infection in guinea pigs

We know that, Favipiravir, also known as T-705 or Avigan, is an experimental antiviral drug being developed by Toyama Chemical of Japan with activity against many RNA viruses. Like some other experimental antiviral drugs (T-1105 and T-1106), it is a pyrazinecarboxamide derivative. Favipiravir is active against influenza viruses, West Nile virus, yellow fever virus, foot-and-mouth disease virus as well as other flaviviruses, arenaviruses, bunyaviruses and alphaviruses.[1Activity against enteroviruses and Rift Valley fever virus has also been demonstrated.

The mechanism of its actions is thought to be related to the selective inhibition of viral RNA-dependent RNA polymerase.[4] Favipiravir does not inhibit RNA or DNA synthesis in mammalian cells and is not toxic to them.[1]

In 2014, favipiravir was approved in Japan for stockpiling against influenza pandemics

Favipiravir, an investigational antiviral drug currently being tested in West Africa as a treatment for Ebola virus disease, effectively treated Lassa virus infection in guinea pigs, according to a new study from National Institutes of Health (NIH) scientists and colleagues. Lassa fever is endemic to West Africa and affects about 300,000 people annually, killing roughly 5,000. In some parts of Sierra Leone and Liberia, it is believed nearly 15 percent of people admitted to hospitals have Lassa fever, according to the Centers for Disease Control and Prevention. No vaccine or licensed treatment exists for Lassa fever, although ribavirin, licensed for hepatitis C treatment, has been used with limited success. In the new study, published Oct. 12, 2015, in Scientific Reports, favipiravir not only effectively treated guinea pigs infected with Lassa virus, it also worked better than ribavirin.

Two days after infecting groups of guinea pigs with a lethal dose of Lassa virus, the scientists treated the rodents daily for two weeks with either ribavirin, low doses of favipiravir, or high doses of favipiravir. They also evaluated the effect of high-dose favipiravir in the rodents that began treatment five, seven or nine days after infection. All of the animals that received high-dose favipiravir were completely protected from lethal infection; animals treated seven or nine days after infection had begun showing signs of disease, but their conditions quickly improved when treatment began. Those animals in the low-dose favipiravir group showed mild to moderate signs of disease, but those symptoms resolved after about one week of treatment. The animals treated with ribavirin appeared normal during the treatment phase but developed severe disease shortly after treatment ended.

Investigational antiviral drug effectively treats Lassa virus infection in guinea pigs

AbbVie's ABT-493 and ABT-530 achieve high SVR rates in GT1 chronic HCV patients who failed previous therapy with DAAs

ABT-493

ABT-530

ribavirin (RBV

AbbVie, a global biopharmaceutical company, today announced that 91 percent (n=20/22) of genotype 1 (GT1) chronic hepatitis C virus (HCV) infected patients who failed previous therapy with direct-acting antivirals (DAAs) achieved SVR12 with 12 weeks of ABT-493 and ABT-530 with ribavirin (RBV) in the primary intent-to-treat analysis. Additionally, 86 percent (n=19/22) of GT1 patients who received ABT-493 and ABT-530 without RBV, achieved SVR12.[i] SVR12 was achieved in 95 percent of patients with and without RBV (n=20/21, n=19/20; respectively) in a modified intent-to-treat analysis, excluding patients who did not achieve SVR for reasons other than virologic failure.

The results were evaluated in the ongoing MAGELLAN-1 study of AbbVie’s once-daily, investigational, pan-genotypic regimen of co-formulated ABT-493 (300mg) and ABT-530 (120mg) for the retreatment of non-cirrhotic patients with GT1 chronic HCV who have failed previous therapy with DAAs. These data will be presented today at The International Liver Congress™ (ILC) 2016 in Barcelona, Spain.

“Retreatment options for those patients who have previously failed therapy are limited, and present a particular challenge for treating physicians,” said Fred Poordad, M.D., vice president of academic and clinical affairs at The Texas Liver Institute in San Antonio. “The high SVR rates seen in the ongoing MAGELLAN-1 study are significant as they show promise in addressing this particular clinical challenge.”

No patients discontinued treatment due to adverse events, and two patients experienced virologic failure, one from each arm. The most common adverse events (≥10 percent of patients overall; n=44) were headache (30 percent), fatigue (27 percent) and nausea (20 percent).

“While high virologic cure rates have been demonstrated in clinical studies with current DAA regimens, we recognize that not all patients achieve a cure,” said Rob Scott, M.D., vice president, development and chief medical officer, AbbVie. “Through our ongoing clinical development program, we are striving to give HCV patients a potential option for retreatment.”

AbbVie's ABT-493 and ABT-530 achieve high SVR rates in GT1 chronic HCV patients who failed previous therapy with DAAs: AbbVie, a global biopharmaceutical company, today announced that 91 percent (n=20/22) of genotype 1 (GT1) chronic hepatitis C virus (HCV) infected patients who failed previous therapy with direct-acting antivirals (DAAs) achieved SVR12 with 12 weeks of ABT-493 and ABT-530 with ribavirin (RBV) in the primary intent-to-treat analysis.

VIEKIRAX and EXVIERA achieve high SVR rates in GT1 and GT4 hepatitis C virus infected patients

ombitasvir

paritaprevir

ritonavir 

dasabuvir 

ribavirin (RBV).

AbbVie, a global biopharmaceutical company,    announced new real-world data showing 96 percent of genotype 1 (GT1) patients (n=486/505 assessable for analysis) and 100 percent (n=53/53) of genotype 4 (GT4) patients achieved sustained virologic response at 12 weeks post-treatment (SVR12). These data support results seen in Phase 3 clinical trials for chronic GT1 or GT4 hepatitis C virus (HCV) infected patients treated with VIEKIRAX® (ombitasvir/paritaprevir/ritonavir tablets) and EXVIERA® (dasabuvir tablets) with or without ribavirin (RBV).

The analysis also reports safety outcomes from 1,017 people with GT1 or GT4 chronic HCV enrolled in the German Hepatitis C-Registry (DHC-R) who have initiated treatment, representing a diverse group of patients seen in real-world settings being treated with VIEKIRAX and EXVIERA. The results will be presented orally today at The International Liver Congress™ (ILC) 2016 in Barcelona, Spain.

“Real-world studies complement randomized controlled trials and help to further enhance our knowledge of VIEKIRAX and EXVIERA in everyday clinical practice,” said Heiner Wedemeyer, M.D., research group leader, department of gastroenterology, hepatology and endocrinology at Hannover Medical School in Germany. “The effectiveness and safety results shown across a broad cross-section of patients in this particular study provide helpful insight into treatment of real-world patients.”

The safety study population (n=1,017) was reflective of a diversity of patients seen in routine clinical practice, including patients with cirrhosis (22 percent) and those previously treated for HCV (59 percent). More than half of patients (59 percent) were taking medicines for other medical conditions.

“These results provide additional insights that complement the Phase 3 clinical trial data for VIEKIRAX and EXVIERA,” said Rob Scott, M.D., vice president, development and chief medical officer, AbbVie. “We believe further ongoing real-world studies across multiple countries will enrich our understanding of HCV treatment.”

Among the patients included in the safety analysis (n=1,017), the rate of discontinuation due to adverse events (AEs) was low (1.5 percent).1 The most common AEs (≥ 5 percent) were fatigue (24 percent), pruritus (10 percent), headache (9 percent), insomnia (6 percent) and nausea (5 percent). Serious AEs were reported in 1 percent (n=5/480) of patients receiving VIEKIRAX and EXVIERA without RBV and in 3 percent (n=16/537) of patients receiving VIEKIRAX and EXVIERA with RBV. Fifteen patients discontinued treatment due to AEs, while two patients died due to myocardial infarction or stroke, respectively. Both cases were assessed as not related to study treatment.

VIEKIRAX and EXVIERA achieve high SVR rates in GT1 and GT4 hepatitis C virus infected patients: AbbVie, a global biopharmaceutical company, today announced new real-world data showing 96 percent of genotype 1 (GT1) patients (n=486/505 assessable for analysis) and 100 percent (n=53/53) of genotype 4 (GT4) patients achieved sustained virologic response at 12 weeks post-treatment (SVR12).

Harvoni Approved for Chronic Hepatitis C

In continuation of my update on  ledipasvir and sofosbuvir (Harvoni-combination pill) 

Harvoni, a daily pill that treats the most common form of hepatitis C, was approved by the U.S. Food and Drug Administration on Friday.

It's the first combination pill (ledipasvir and sofosbuvir) approved to treat the chronic infection, and the first medication that doesn't require that the antiviral drugs interferon or ribavirin be taken at the same time, the FDA said in a news release.

Both drugs in the combination pill interfere with the hepatitis C virus' ability to multiply. One of the drugs, sofosbuvir (Sovaldi) was approved in December 2013, while ledipasvir is a new antiviral, the agency said.

"With the development and approval of new treatments for hepatitis C virus, we are changing the treatment paradigm for Americans living with the disease," Dr. Edward Cox, director of the Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research, said in the news release. "Until last year, the only available treatments for hepatitis C virus required administration with interferon and ribavirin. Now, patients and health care professionals have multiple treatment options, including a combination pill to help simplify treatment regimens."

One expert applauded Harvoni's approval.

"This is a giant step forward for people with [hepatitis C]. One pill, once daily, no interferon, no ribavirin and 94 to 99 percent cure! It moves the risk-benefit ratio needle way over toward benefit," said Dr. Douglas Dieterich, a professor of medicine in the division of liver diseases at The Mount Sinai Hospital in New York City.

However, price has been an issue with some of the new treatments for hepatitis C. For example, Sovaldi alone costs $1,000 a day and not all insurance companies cover the cost of treatment, experts have noted. Harvoni will cost $1,125 a pill, the Associated Press reported Friday.

Hepatitis C causes inflammation of the liver, which could spark other problems including diminished liver function (cirrhosis), scarring, liver cancer or liver failure. Most infected people aren't aware that they carry the virus until liver damage has occurred, the agency said.

Some 3.2 million Americans are believed to be infected with hepatitis C, the FDA said.

Harvoni was evaluated in three clinical studies involving more than 1,500 people who either hadn't been treated previously or hadn't responded to prior treatment. The most common side effects were fatigue and headache.

Harvoni Approved for Chronic Hepatitis C  

FDA Approves Expanded Use of Daklinza (daclatasvir) for Additional Challenging-to-treat Patients with Genotype 1 or Genotype 3 Chronic Hepatitis C

In continuation  of my update on Daclatasvir

Bristol-Myers Squibb Company (NYSE:BMY) announced today that Daklinza (daclatasvir, 60 mg), an NS5A replication complex inhibitor, has been approved by the U.S. Food and Drug Administration (FDA) in combination with sofosbuvir (with or without ribavirin) in genotypes 1 and 3. The expanded label includes data in three additional challenging-to-treat patient populations: chronic hepatitis C virus (HCV) patients with HIV-1 coinfection, advanced cirrhosis, or post-liver transplant recurrence of HCV. The Daklinza plus sofosbuvir regimen is already available for the treatment of chronic HCV genotype 3, and is currently the only 12-week, once-daily all-oral treatment option for these patients. Sustained virologic response (SVR) rates are reduced in genotype 3 patients with cirrhosis receiving Daklinza and sofosbuvir for 12 weeks without ribavirin. The recommended dosage of Daklinza is 60 mg in combination with sofosbuvir with or without (+/-) ribavirin for 12 weeks..

“The expanded indication for Daklinza offers an additional treatment option for multiple subsets of patients who have genotype 1 or 3 chronic HCV,” said Chris Boerner, Head of U.S. Commercial, Bristol-Myers Squibb. “HCV/HIV-coinfected patients and patients with advanced cirrhosis or post-transplant recurrence of HCV still pose a treatment challenge to physicians. As part of our commitment to the HCV community, we have sought to make new treatment options available for these and other targeted populations that have not yet been able to fully benefit from currently available next-generation medicines.”

FDA Approves Expanded Use of Daklinza (daclatasvir) for Additional Challenging-to-treat Patients with Genotype 1 or Genotype 3 Chronic Hepatitis C

FDA Approves Expanded Use of Daklinza (daclatasvir) for Additional Challenging-to-treat Patients with Genotype 1 or Genotype 3 Chronic Hepatitis C

In continuation of my update on daclatasvir

Bristol-Myers Squibb Company (NYSE:BMY) announced today that Daklinza (daclatasvir, 60 mg), an NS5A replication complex inhibitor, has been approved by the U.S. Food and Drug Administration (FDA) in combination with sofosbuvir (with or without ribavirin) in genotypes 1 and 3. The expanded label includes data in three additional challenging-to-treat patient populations: chronic hepatitis C virus (HCV) patients with HIV-1 coinfection, advanced cirrhosis, or post-liver transplant recurrence of HCV. The Daklinza plus sofosbuvir regimen is already available for the treatment of chronic HCV genotype 3, and is currently the only 12-week, once-daily all-oral treatment option for these patients. Sustained virologic response (SVR) rates are reduced in genotype 3 patients with cirrhosis receiving Daklinza and sofosbuvir for 12 weeks without ribavirin. The recommended dosage of Daklinza is 60 mg in combination with sofosbuvir with or without (+/-) ribavirin for 12 weeks.

FDA Approves Expanded Use of Daklinza (daclatasvir) for Additional Challenging-to-treat Patients with Genotype 1 or Genotype 3 Chronic Hepatitis C

New Anti-Viral Drug Shows Promise for Dramatic Improvement in Hepatitis C Treatment

Research team, led by Paul Kwo, M.D., of Indiana University School of Medicine, reported that adding the drug boceprevir, nearly doubled the treatment's effectiveness when given for 48 weeks in one treatment arm of the study. We knew that, Boceprevir (see structure) is a protease inhibitor being studied as a treatment for hepatitis C. It was being developed by Schering-Plough and has since been absorbed into the Merck's new pipeline since its acquired Schering in 2009. As of 2008, it is in phase II clinical trials (SPRINT-1 trial). Researchers claim that, adding a direct acting anti-viral drug to the standard treatment regimen for hepatitis C significantly increases the cure rate in the most difficult to treat patients.

Researchers claim that, the drug boceprevir increased the cure rate to as high as 75 percent in those who received 48 weeks of the three-drug combination therapy, compared to 38 percent of those in the control group, who received the standard two-drug treatment (peginterferon alfa-2b plus ribavirin)   for 48 weeks, said Dr. Kwo, associate professor of medicine at the IU School of Medicine. The two-year phase 2 trial was conducted at 67 sites with 520 patients in the US, Canada and Europe.

In the boceprevir study, known as the SPRINT-1 trial, researchers tested several different options to evaluate the effectiveness of the combination therapy.

"Both 28- and 48-week boceprevir regimens significantly increased sustained virologic response rates  which is the best definition of a cure we have  compared to the 48 week control," said Dr. Kwo. "The 48-week treatment arm with 4 weeks of peg interferon lead-in and 44 weeks of peg interferon, ribavirin, and boceprevir led to the largest improvement over the control group ever reported. That's very impressive." 

Researchers conclude that, best results were reported for the 103 patients who were treated for four weeks with the standard two drug regiment, followed by 44 weeks of the three-drug regimen including boceprevir: 75 percent of these patients tested negative for evidence of the virus six months after the end of treatment.

As per the lead researcher, Dr. Kwo, based on this phase 2 study, it appears that if this drug receives final approval approximately two-thirds of patients will be able to be treated successfully with 28 weeks of treatment and one-third will need 48 weeks of treatment, though this will require confirmation from the phase 3 trials, from which preliminary results were recently released.

Ref  : http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2960934-8/fulltext

New combination drug therapy proves very effective in hepatitis C treatments

A new 12-week single tablet regimen of ledipasvir and sofosbuvir have proven to be highly effective in treating a broad range of patients with HCV genotype 1, a form of the virus found in up to 75 percent of infections, according to results unveiled today at the European Association for the Study of the Liver and published simultaneously online by the New England Journal of Medicine.

Between 94 percent and 99 percent of patients were cured of hepatitis C and results were similar in patients who have never been treated and for those who had previously been treated with a combination of peginterferon and ribavirin, the current course that carries sometimes significant side effects.

“Eliminating interferon and ribavirin from treatment regimens is expected to reduce the incidence and severity of adverse events, to simplify the treatment of patients with HCV infection and to provide an option for patients who are ineligible for the current interferon-based treatments,” said Nezam Afdhal, MD, the senior author of the studies, Director of the Liver Center at Beth Israel Deaconess Medical Center and a Professor of Medicine at Harvard Medical School.

Hepatitis C is an infectious disease primarily affecting the liver and which can lead to scarring and cirrhosis and is transmitted primarily through blood transfusions (prior to 1991), intravenous drug use, poorly sterilized medical equipment and sexual transmission.. After exposure 80 percent of patients develop a chronic hepatitis which can lead to cirrhosis, liver failure and liver cancer and hepatitis C is the most common cause for liver transplantation in the US.

Prior treatments have been with interferon which is an injectable cytokine released in response to viral infections. Interferon is combined with other antiviral agents and needs to be used for up to 48 weeks to cure hepatitis C. but is associated with number of side effects, including influenza-like symptoms depression and anemia. Many patients are ineligible for these interferon-based therapies.

“The real advances seen in the Ion trials is that the sofosbuvir-ledipasvir combination tablet enables us to treat almost all genotype 1 patients with a short duration of 8-12 weeks of treatment expanding the treatment pool and increasing the overall cure rate,” said Afdhal.

New combination drug therapy proves very effective in hepatitis C treatments

Telaprevir-based regimens increase rates of SVR in patients with genotype 1 HCV infection

In continuation of my update on telaprevir-based regimens, I found this article interesting to share with.....

In a clinical trial known as PROVE 3 published in this week's New England Journal of Medicine, treatment with telaprevir-based regimens significantly increased rates of sustained viral response (SVR) in patients with genotype 1 hepatitis C virus (HCV) infection who did not achieve SVR with at least one prior course of pegylated-interferon and ribavirin therapy. In the trial, 51 percent and 53 percent of patients who received telaprevir in combination with pegylated-interferon and ribavirin as part of a 24-week or 48-week regimen, respectively, achieved SVR.   More...

New drug combination may reduce need for complex regimens to treat hepatitis C

In continuation of my update on sofosbuvir

  

The prognosis for people with hepatitis C has improved dramatically in the last few years, thanks to the introduction of direct-acting anti-viral medications, including Harvoni (the brand name for a combination of ledipasvir and sofosbuvir) and Viekira Pack (a mix of ombitasvir, paritaprevir, ritonavir and dasabuvir). These drugs — which block the hepatitis C virus from multiplying — boast cure rates of better than 90 percent. In addition, they are well-tolerated in most patients, causing only minor side effects.

Despite these major advances, the quest for better hepatitis C medications is not yet over. Drug makers continue to test new drugs to overcome limitations in treating this virus, which can cause liver cirrhosis (or scarring) and failure. About 2.7 million people in the U.S. are infected with the virus, with nearly 30,000 cases occurring in 2013 alone, according to the Centers for Disease Control and Prevention.

"The current medicines are very effective, but physicians sometimes have to tailor the regimen or the length of treatment based on patient characteristics, such as whether the patient has liver cirrhosis or has failed prior therapy," says Nancy S. Reau, MD, chief of the Section of Hepatology at Rush University Medical Center.

Another treatment factor is the type of hepatitis C a patient has. The virus has six different strains, called genotypes.

Now a simplified way of treating all hepatitis C patients may be approaching. Reau participated in a phase III clinical trial of a combination of Solvadi (sofosbuvir) with the investigational drug velpatasvir on patients with genotypes two and three. As described in an article published online on Nov. 17 in the New England Journal of Medicine, the study found that 12 weeks of sofosbuvir-velpatasvir produced higher cure rates in patients with these two genotypes — including those who had cirrhosis or had failed older treatments — than a similar therapy (sofosbuvir-ribavirin)

New drug combination may reduce need for complex regimens to treat hepatitis C

Triple-combo Drug for Antiviral-resistant H1N1 ?

In laboratory testing, the triple combination of oseltamivir (Tamiflu), amantadine (Symmetrel) and ribavirin showed a significant capacity to stop flu-virus growth, says Mark Prichard....

More...http://www.sciencedaily.com/releases/2009/10/091027132426.htm

EC approves expanded use of Daklinza (daclatasvir) for patients with chronic HCV and HIV co-infection

Daclatasvir formerly BMS-790052, trade name Daklinza) is a drug for the treatment of hepatitis C (HCV). It was developed by Bristol-Myers Squibb and was approved in Europe on 22 August 2014. Daklinza gained its FDA approval on July 24, 2015 in the United States; it is approved for Hepatitis C genotype 3 infections.  

A generic version of daclatasvir is expected to be approved in India before the end of 2015. 

Daclatasvir inhibits the HCV nonstructural protein NS5A.  Recent research suggests that it targets two steps of the viral replication process, enabling rapid decline of HCV RNA. Daclatasvir has been tested in combination regimens with pegylated interferon and ribavirin,  as well as with other direct-acting antiviral agents including asunaprevir and sofosbuvir....

Now....

EC approves expanded use of Daklinza (daclatasvir) for patients with chronic HCV and HIV co-infection: Bristol-Myers Squibb today announced that the European Commission has approved the expanded use of Daklinza, a first-in-class oral, once-a-day pill used in combination with other treatments as an option for adult patients with chronic hepatitis C virus infection who are co-infected with HIV or who have had a prior liver transplant.

New treatment regimen for hepatitis C in transplant patients produces promising results

The investigational three-drug regimen, which produced hepatitis C cure rates of 97 percent, is an oral interferon-free therapy. Previously, the typical treatment for hepatitis C after a liver transplant was an interferon-based therapy, usually given for 48 weeks. It had a much lower response rate, had a risk of organ rejection and was poorly tolerated because of the immunosuppressants required to prevent rejection. The new oral regimen -- ABT-450, ombitasvir and dasabuvir (with or without ribavirin) -- produces significantly fewer side effects and is prescribed for 24 weeks.

New treatment regimen for hepatitis C in transplant patients produces promising results

SPC3649 ( LNA- locked nucleic acid) - a new hope for hepatitis C.....

When  I was working with Innovasynth Technologies, Khopoli, I had an opportunity to do literature survey about  Lock Nucleic Acids (LNAs) and Peptide Nucleic Acids (PNAs) (we were supposed to work on the preparation of  some of the LNAs & PNAs for US based companies). In my opinion though these class of compounds (including oligonucleotides) are  still emerging,  I think in the days to come there will be more and more drugs from oligonucleotides, Locked Nucleic Acids (LNAs) and Peptide Nucleic Acids, (PNAs) class of compounds.

LNAs : A locked nucleic acid (LNA) (see the right side general structure), is a modified RNA nucleotide. Ribose moiety of an LNA nucleotide is modified with an extra bridge

connecting the 2' oxygen and 4' carbon. The bridge "locks" the ribose  in the 3'-endo (North) conformation, which is often found in the A-form of DNA or RNA. LNA nucleotides can be mixed with DNA or RNA bases in the oligonucleotide whenever desired. This locking  significantly increases the thermal stability (mp) of oligonucleotide.

LNA nucleotides are used to increase the sensitivity and specificity of expression in DNA microarrays, FISH probes, real-time PCR probes and other molecular biology techniques based on oligonucleotides. For the in situ detection of miRNA the use of LNA is currently the only efficient method. A triplet of LNA nucleotides surrounding a single-base mismatch site maximizes LNA probe specificity unless the probe contains the  G-T mismatch. We have already seen some antisense drugs (oligonucleotides from Geron & Isis) and some are into clinical trials.

Now its interesting to see that Santaris Pharma   is currently advancing LNA based compounds within infectious diseases, metabolic disorders, oncology, inflammatory and rare genetic disorders.

Santaris Pharama, has developed a LNA,  SPC3649 - which captures a small RNA molecule in the liver, called microRNA122, that is required for HCV replication.

As per the claim by the company, SPC3649 works by altering the environment in the host liver cell to inhibit viral replication rather than inhibiting the virus itself. This subtle difference (in comparison  with other therapies) may have significant implications, as it may reduce the risk of the virus becoming resistant to therapy – a major concern with current therapies.

As per the claim by Dr. Robert Lanford,  (who has collaboration with Santaris Pharma), that in a preclinical study  SPC3649 successfully inhibited miR-122, a liver-expressed microRNA important for Hepatitis C viral replication. By inhibiting miR-122, SPC3649 dramatically reduced Hepatitis C virus in the liver and in the bloodstream in chimpanzees chronically infected with the Hepatitis C virus. Four HCV chronically infected chimpanzees were treated weekly with 5 or 1 mg/kg of SPC3649 for 12 weeks followed by a treatment free period of 17 weeks. The two animals that received the 5 mg/kg dose had a significant decline in viral levels in the blood and liver of approximately 2.5 orders of magnitude or approximately 350 fold. Hope the new therapy could potentially replace interferon (interferon and ribavirin is  approved by FDA for hepatitis C and this treatment is very toxic, requires 48 weeks with 50% success) in future cocktails, since it provides a high barrier to resistance. This antiviral could be used alone to treat disease progression and there are indications that it can convert interferon non-responders to responders, so that non-responders to the current therapy could be treated with the combination of this drug with interferon.   More....

Those interested  can see the video demo with the link

FDA Approves Zepatier (elbasvir and grazoprevir) for Chronic Hepatitis C Genotypes 1 and 4

 (Elbasvir) 

 (Grazoprevir)

The U.S. Food and Drug Administration today approved Zepatier (elbasvir and grazoprevir) with or without ribavirin for the treatment of chronic hepatitis C virus (HCV) genotypes 1 and 4 infections in adult patients.

Hepatitis C is a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure. Most people infected with HCV have no symptoms of the disease until liver damage becomes apparent, which may take several years. Some people with chronic HCV infection develop cirrhosis over many years, which can lead to complications such as bleeding, jaundice (yellowish eyes or skin), fluid accumulation in the abdomen, infections or liver cancer. According to the Centers for Disease Control and Prevention, approximately 3 million Americans are infected with HCV, of which genotype 1 is the most common and genotype 4 is one of the least common.

“Today’s approval provides another oral treatment option for patients with genotypes 1 and 4 HCV infections without requiring use of interferon,” said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research.

FDA Approves Zepatier (elbasvir and grazoprevir) for Chronic Hepatitis C Genotypes 1 and 4

Telaprevir for Hepatitis C, soooon...

We did know that Telaprevir (VX-950), is a member of a class of antiviral drugs known as 'Protease Inhibitors' was an experimental treatment for Hepatitis and two companies Vertex and Johnson & Johnson jointly developed and phase II clinical trials were being done. Now thanx, to Dr. Ira M. Jacobson chief of the Division of Gastroenterology and Hepatology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, and the Vincent Astor Distinguished Professor of Clinical Medicine at Weill Cornell Medical College, who has come up with the results of Phase IIb clinical trial.

Th results are really encouraging and as per the author, "the findings point the way to a new era in the treatment of hepatitis C". The most significant part of the research lies in the fact that, by adding Telaprevir the treatment was more effective and quicker and there by reducing the therapy to half (from 48 weeks to 24 weeks).

Results showed that 67 percent of patients taking telaprevir in combination with standard therapy for 12 weeks followed by standard therapy alone for 36 weeks were cured; and 61 percent of those taking telaprevir in combination with standard therapy for 12 weeks followed by standard therapy alone for 12 weeks were cured. This is compared to 41 percent cure rate in the 48-week control group. And more over the study also showed that the percentage of patients who relapsed in the 24-week and 48-week telaprevir-based groups (2 percent and 6 percent, respectively) was much lower than the control group (23 percent). Also the authors found that it can be used alongwith Ribavirin, for those with HIV & Hepatitis C. Congratulations for this achievement. Phase III clinical trials are currently underway at the NewYork-Presbyterian/Weill Cornell and centers worldwide will attempt to confirm the results, potentially leading to FDA approval of telaprevir and hope there will be a relief to the sufferers very soooon......

Ref : http://news.med.cornell.edu/wcmc/wcmc_2009/06_04_09.shtml

FDA Approves Two Supplemental Indications for Harvoni in Chronic Hepatitis C Patients With Advanced Liver Disease

In continuation of my update on Harvoni (ledipasvir/sofosbuvir)

Gilead Sciences, Inc. (NASDAQ: GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved additional indications for Harvoni (ledipasvir/sofosbuvir) for use in chronic hepatitis C patients with advanced liver disease. Harvoni in combination with ribavirin (RBV) for 12 weeks was approved for use in chronic hepatitis C virus (HCV) genotype 1- or 4-infected liver transplant recipients without cirrhosis or with compensated cirrhosis (Child-Pugh A), and for HCV genotype 1-infected patients with decompensated cirrhosis (Child-Pugh B or C), including those who have undergone liver transplantation. Harvoni is now approved for use in a broader range of patient populations, including HCV genotypes 1, 4, 5 and 6, HCV/HIV-1 coinfection, HCV genotype 1 and 4 liver transplant recipients, and genotype 1-infected patients with decompensated cirrhosis..

FDA Approves Two Supplemental Indications for Harvoni in Chronic Hepatitis C Patients With Advanced Liver Disease

Olysio (simeprevir) Approved By FDA To Treat Hepatitis C Virus | MediMoon

We know that, Simeprevir (see structure below, formerly TMC435; trade name Olysio) is a drug for the treatment and cure of hepatitis C. It was developed by Medivir and Johnson & Johnson's pharmaceutical division Janssen Pharmaceutica. In the United States, simeprevir is approved by the Food and Drug Administration for use in combination withpeginterferon-alfa and ribavirin. Simeprevir has been approved in Japan for the treatment of chronic hepatitis C infection, genotype 1

Olysio (simeprevir) Approved By FDA To Treat Hepatitis C Virus | MediMoon