Hepatitis C - New Therapies Are Coming Soon: The Case To Wait

New Therapies Are Coming Soon:  The Case To Wait

Good morning folks, sit back and watch an entertaining webcast presented in a trial and jury format, which examines the "Treat Now Or Wait" scenario in patients with HCV.

The program was recently launched for your viewing pleasure over at CLDF, listen to the judge and expert witnesses discuss new HCV regimens under development with or without ribavirin in this light-hearted innovative presentation.

Click here..........

More On: Daclatasvir (Daklinza) for Chronic Hepatitis C Cleared in EU

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Daclatasvir (Daklinza) for Chronic Hepatitis C Cleared in EU
Medscape
The European Commission has approved daclatasvir (Daklinza, Bristol-Myers Squibb) to treat adults with chronic hepatitis C virus (HCV) infection in combination with other drugs, the company announced today.

The approval follows an endorsement in June by the European Medicines Agency Committee for Medicinal Products for Human Use.

Daclatasvir blocks the action of NS5A, a protein essential for HCV replication. It is indicated for adults infected with HCV genotypes 1, 2, 3, and 4.

In a news release, the company notes that oral daclatasvir in combination with oral sofosbuvir provided cure rates of up to 100% in clinical trials, including in patients with advanced liver disease, genotype 3, and those who have previously failed treatment with protease inhibitors.

Daclatasvir is the first NS5A complex inhibitor approved in the European Union (EU) and, in combination with other drugs, provides a "shorter treatment duration (12 or 24 weeks) compared to 48 weeks of treatment with interferon- and ribavirin-based regimens," the company says.

Across clinical studies, daclatasvir-based regimens have been generally well-tolerated, with low discontinuation rates. The most common adverse effects with daclatasvir when used in combination with other drugs are fatigue, headache, and nausea.

The safety of daclatasvir has been demonstrated in diverse patient populations that include elderly patients, patients with advanced liver disease, post–liver transplant recipients, and patients coinfected with HIV, the company says.

"HCV is a challenging virus to overcome," Michael P. Manns, MD, professor and chairman, Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Germany, said in the release. Daclatasvir, when combined with other compounds, "often results in cure among even the hardest-to-treat patients," he added.

Recommended regimens and treatment durations for daclatasvir-based regimens include:
  • For HCV genotype 1 or 4 without cirrhosis: daclatasvir plus sofosbuvir for 12 weeks. Consider prolongation to 24 weeks for patients with prior treatment, including a NS3/4A protease inhibitor.
  • For genotype 1 or 4 with compensated cirrhosis: daclatasvir plus sofosbuvir for 24 weeks. Consider shortening treatment to 12 weeks for previously untreated patients with cirrhosis and positive prognostic factors such as IL28B CC genotype and/or low baseline viral load. Consider adding ribavirin for patients with very advanced liver disease or with other negative prognostic factors, such as prior treatment experience.
  • For genotype 3 with compensated cirrhosis and/or treatment experienced: daclatasvir plus sofosbuvir plus ribavirin for 24 weeks.
  • For genotype 4: 24 weeks of daclatasvir plus 24 to 48 weeks of peginterferon alfa and ribavirin. If the patient has HCV RNA undetectable at both treatment weeks 4 and 12, all 3 components of the regimen should be continued for 24 weeks. If the patient achieves undetectable HCV RNA, but not at both treatment weeks 4 and 12, daclatasvir should be discontinued at 24 weeks and peginterferon alfa and ribavirin continued for a total duration of 48 weeks.
Daclatasvir monotherapy is not recommended. The Summary of Product Characteristics will be available online. Commercial availability of daclatasvir in the EU will be determined by individual member states.

Bristol-Myers Squibb’s Daklinza (daclatasvir), Approved By European Commission

European Commission Approves Bristol-Myers Squibb’s Daklinza (daclatasvir) Across Multiple Genotypes for the Treatment of Chronic Hepatitis C Infection

Daklinza, when used in combination with sofosbuvir, is an all-oral, once daily regimen that yields cure rates of up to 100%

Daklinza + sofosbuvir offers potential cure for a broad range of EU HCV patients, including those with advanced liver disease, genotype 3 and protease inhibitor failures

R&D News

Wednesday, August 27, 2014 5:00 am EDT
"The eradication of HCV is in sight, and with today’s approval, Daklinza, in combination with other agents, will be an important option to achieve cure across many HCV genotypes and patient types for those in the EU who are in dire need of new treatment choices"
PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced that the European Commission has approved Daklinza (daclatasvir), a potent, pan-genotypic NS5A replication complex inhibitor (in vitro), for use in combination with other medicinal products across genotypes 1, 2, 3 and 4 for the treatment of chronic hepatitis C virus (HCV) infection in adults. Daklinza, when used in combination with sofosbuvir, is an all-oral, interferon-free regimen that provided cure rates of up to 100% in clinical trials, including patients with advanced liver disease, genotype 3 and those who have previously failed treatment with protease inhibitors. Daklinza is the first NS5A complex inhibitor approved in the European Union (EU) and will be available for use in combination with other medicinal products, providing a shorter treatment duration (12 or 24 weeks) compared to 48 weeks of treatment with interferon- and ribavirin-based regimens.

Today’s approval allows for the marketing of Daklinza in all 28 Member States of the EU. The marketing authorization for Daklinza follows an accelerated assessment by the Committee for Medicinal Products for Human Use (CHMP), a designation that is granted to new medicines of major public health interest.

“HCV is a challenging virus to overcome, requiring multiple modes of attack. With the approval of Daklinza, we have a new class of drug that disrupts the virus in two ways - by inhibiting both viral replication and assembly - and when combined with other compounds often results in cure among even the hardest-to-treat patients,” said Michael P. Manns, MD, Professor and Chairman, Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.

Of the estimated nine million people living with HCV in the EU, genotype 1 is the most common genotype, though distribution varies across the region. The burden of liver disease and other morbidities from HCV infection is significant in Europe, where HCV accounts for 63% of liver transplants among patients with virus-related liver disease. Patient populations with high unmet needs include those with advanced liver disease, protease inhibitor failure, genotype 3, HIV co-infected patients and those who have undergone liver transplant.

“The eradication of HCV is in sight, and with today’s approval, Daklinza, in combination with other agents, will be an important option to achieve cure across many HCV genotypes and patient types for those in the EU who are in dire need of new treatment choices,” said Emmanuel Blin, Head of Worldwide Commercialization, Bristol-Myers Squibb. “We are proud to have discovered, developed and now brought to market this first-in-class NS5A replication complex inhibitor. We look forward to our continued work with EU health authorities to ensure Daklinza-based regimens are available to patients as quickly as possible.”
The approval of Daklinza is supported by data from multiple studies, including an open-label, randomized study of Daklinza with sofosbuvir in genotypes 1, 2, and 3, including patients with no response to prior therapy with telaprevir or boceprevir and patients with fibrosis. Results showed that a regimen of Daklinza with sofosbuvir achieved SVR12 (sustained virologic response 12 weeks after the end of treatment; a functional cure) in 99% of treatment-naïve patients with HCV genotype 1, 100% of patients with genotype 1 who had failed treatment with either telaprevir or boceprevir, 96% of those with genotype 2 and 89% of those with genotype 3.

In addition, the regimen resulted in low rates of discontinuation (<1%) due to adverse events (AEs). The rate of serious adverse events (SAEs) was low (4.7%). The most common adverse events were fatigue, headache and nausea. Across clinical studies, Daklinza-based regimens have been generally well tolerated with low rates of discontinuation across a range of patients. Ongoing and completedDaklinza studies have included more than 5,500 patients in a variety of all-oral regimens and with the current interferon-based standard of care.

The safety of Daklinza for the treatment of hepatitis C has been demonstrated in diverse patient populations that include elderly patients, patients with advanced liver disease, post-liver transplant recipients and patients co-infected with HIV. No unique safety concerns have been identified in patients who were treated withDaklinza across clinical studies and in the early access program. Several of these studies are ongoing.

Recommended regimens and treatment duration for Daklinza combination therapy include:
HCV genotype and patient populationTreatmentDuration
Genotype 1 or 4 without cirrhosis
Daklinza + sofosbuvir
12 weeks
Consider prolongation of treatment to 24 weeks for patients with prior treatment including a NS3/4A protease inhibitor (see sections 4.4 and 5.1).
Genotype 1 or 4 with compensated cirrhosisDaklinza + sofosbuvir24 weeks
Shortening treatment to 12 weeks may be considered for previously untreated patients with cirrhosis and positive prognostic factors such as IL28B CC genotype and/or low baseline viral load.
Consider adding ribavirin for patients with very advanced liver disease or with other negative prognostic factors such as prior treatment experience.
Genotype 3 with compensated cirrhosis and/or treatment experiencedDaklinza + sofosbuvir + ribavirin24 weeks
Genotype 4Daklinza + peginterferon alfa + ribavirin24 weeks of Daklinza in combination with 24-48 weeks of peginterferon alfa and ribavirin.
If the patient has HCV RNA undetectable at both treatment weeks 4 and 12, all 3 components of the regimen should be continued for a total duration of 24 weeks. If the patient achieves HCV RNA undetectable, but not at both treatment weeks 4 and 12, Daklinza should be discontinued at 24 weeks and peginterferon alfa and ribavirin continued for a total duration of 48 weeks.
Daklinza monotherapy is not recommended. The Summary of Product Characteristics will be available at www.ema.europa.eu. Commercial availability of Daklinza in the EU will be determined by individual Member States.

Investment Commentary

Bristol-Myers gets the approval Gilead didn't want: Daklinza + Sovaldi for hep C
And here's where it gets more interesting. We know Gilead will be leaning on its Sovaldi + ledipasvir pill, which is up for FDA approval by Oct. 10. AbbVie's three-drug option is under FDA review for a December decision. Bristol-Myers might want to tout the Daklinza + Sovaldi option when (and if) its FDA nod comes through in November.
But the FDA didn't allow the company to turn in that Sovaldi-Daklinza data with its current app. The approval would be for Daklinza and another BMS drug, Sunvepra (asunaprevir)--and that combo hasn't performed quite as well as the Daklinza-Sovaldi team in trials. Sustained virological response--a common measure in hep C trials--for the latter duo approached 100% in some patients, as Bristol-Myers noted in its E.U. announcement.....
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Medscape

More On: Daclatasvir (Daklinza) for Chronic Hepatitis C Cleared in EU

"HCV is a challenging virus to overcome," Michael P. Manns, MD, professor and chairman, Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Germany, said in the release. Daclatasvir, when combined with other compounds, "often results in cure among even the hardest-to-treat patients," he added.
Continue reading.....