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 population | Treatment | Duration | ||||
| 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 cirrhosis | Daklinza + sofosbuvir | 24 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 experienced | Daklinza + sofosbuvir + ribavirin | 24 weeks | ||||
| Genotype 4 | Daklinza + peginterferon alfa + ribavirin | 24 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
Medscape
More On: Daclatasvir (Daklinza) for Chronic Hepatitis C Cleared in EU
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.....Continue reading...
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.....
MSF urges BMS to make daclatasvir accessible in low-and middle-income countries
Ramesh Shankar, Mumbai
Saturday, August 30, 2014, 08:00 Hrs [IST]
Even as the European Commission (EC) and European Medicines Agency (EMA) approved the new direct-acting antiviral (DAA) daclatasvir to treat hepatitis C, the international medical humanitarian organization Médecins Sans Frontières (MSF) has asked the Bristol-Myers Squibb (inventor of daclatasvir) to ensure that people living with hepatitis C in low- and middle-income countries can actually access this important drug, so that it can have the greatest impact on hepatitis C globally in helping to cure people.
Welcoming the EMA's approval of daclatasvir on August 27, 2014, the MSF said that the BMS must rapidly register daclatasvir in those countries with a high burden of hepatitis C, especially in those countries with a high prevalence of genotype 3. It also urged BMS to ensure daclatasvir is affordable in those countries with a high burden of hepatitis C.
“Intellectual property barriers for daclatasvir, unless they are overcome, could keep affordable versions out of reach of people and may also prevent the development of an optimal fixed-dose combination that can provide simple, highly effective treatment for all people with hepatitis C, regardless of genotype”, said Dr Jennifer Cohn, medical director, MSF Access Campaign.
“Patent barriers that prevent affordable access to daclatasvir and the new DAAs must be addressed by governments to promote robust generic competition, which will enable price reductions, facilitate the development of a pan-genotypic combination, and accelerate availability in all developing countries that are bearing the brunt of the hepatitis C epidemic,” Dr Cohn further said.
On 27 August 2014, the EC and the EMA became the second regulatory authority (after Japan in July) to approve new direct-acting antiviral (DAA) daclatasvir, used to treat hepatitis C. Daclatasvir is the third DAA - a new class of oral drugs used to treat hepatitis C – to be approved.
The approval of daclatasvir is medically significant, as it, in combination with other hepatitis C drugs including other DAAs, results in high cure rates; clinical trials have also shown it to be well tolerated by people. In addition, combining two DAAs is critical to simplifying treatment in developing countries, and combinations which include daclatasvir, such as sofosbuvir+daclatasvir, have pan-genotypic potential; daclatasvir has shown to be effective for genotype 3, which has proven difficult to treat with other DAAs and is highly prevalent among people living with hepatitis C in India and Pakistan.
However, the MSF expressed its concern about the potential lack of affordable access to daclatasvir, and patent barriers that could prevent the development of effective and affordable combinations.
Development and testing of sofosbuvir/daclastavir combination treatment was delayed when Gilead (owner of sofosbuvir) stopped collaboration with Bristol-Myers Squibb (owner of daclatasvir) in favour of Gilead's proprietary sofosbuvir/GS-5816 combination. Only now is BMS able to undertake phase III trials of this combination with commercially available sofosbuvir. Further, BMS has not yet announced any access plans for low- and middle-income countries, where the majority of the hepatitis C burden lies.
Welcoming the EMA's approval of daclatasvir on August 27, 2014, the MSF said that the BMS must rapidly register daclatasvir in those countries with a high burden of hepatitis C, especially in those countries with a high prevalence of genotype 3. It also urged BMS to ensure daclatasvir is affordable in those countries with a high burden of hepatitis C.
“Intellectual property barriers for daclatasvir, unless they are overcome, could keep affordable versions out of reach of people and may also prevent the development of an optimal fixed-dose combination that can provide simple, highly effective treatment for all people with hepatitis C, regardless of genotype”, said Dr Jennifer Cohn, medical director, MSF Access Campaign.
“Patent barriers that prevent affordable access to daclatasvir and the new DAAs must be addressed by governments to promote robust generic competition, which will enable price reductions, facilitate the development of a pan-genotypic combination, and accelerate availability in all developing countries that are bearing the brunt of the hepatitis C epidemic,” Dr Cohn further said.
On 27 August 2014, the EC and the EMA became the second regulatory authority (after Japan in July) to approve new direct-acting antiviral (DAA) daclatasvir, used to treat hepatitis C. Daclatasvir is the third DAA - a new class of oral drugs used to treat hepatitis C – to be approved.
The approval of daclatasvir is medically significant, as it, in combination with other hepatitis C drugs including other DAAs, results in high cure rates; clinical trials have also shown it to be well tolerated by people. In addition, combining two DAAs is critical to simplifying treatment in developing countries, and combinations which include daclatasvir, such as sofosbuvir+daclatasvir, have pan-genotypic potential; daclatasvir has shown to be effective for genotype 3, which has proven difficult to treat with other DAAs and is highly prevalent among people living with hepatitis C in India and Pakistan.
However, the MSF expressed its concern about the potential lack of affordable access to daclatasvir, and patent barriers that could prevent the development of effective and affordable combinations.
Development and testing of sofosbuvir/daclastavir combination treatment was delayed when Gilead (owner of sofosbuvir) stopped collaboration with Bristol-Myers Squibb (owner of daclatasvir) in favour of Gilead's proprietary sofosbuvir/GS-5816 combination. Only now is BMS able to undertake phase III trials of this combination with commercially available sofosbuvir. Further, BMS has not yet announced any access plans for low- and middle-income countries, where the majority of the hepatitis C burden lies.
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