The Canadian Agency for Drugs and Technologies in Health (CADTH) announced last week that they had received notices of pending Common Drug Review submissions from Bristol-Myers Squibb for asunaprevir and daclatasvir, two of their hep C treatments.
Within their announcement, CADTH also stated that the patient group input reports for these two potential treatments are due in early March.
For asunaprevir and daclatasvir, this means a new step has been reached on their way through the drug approval process towards approval. For you, it means an opportunity to have your voices and stories heard is imminent!
As a precursor to that, the Hepatitis C Treatment Information Project has put together the following treatment summary. The following treatment summary includes information not only about asunaprevir and daclatasvir, but also about beclabuvir. Beclabuvir is another Bristol-Myers Squibb direct-acting antiviral making its way through the hep C drug pipeline. We included it in this summary as all three drugs have been studied together in a number of different clinical trials.
The Hepatitis C Treatment Information Project’s Hep C Treatment page includes more information about direct-acting antivirals (DAAs).
Asunaprevir, Daclatasvir, and Beclabuvir
- Asunaprevir (a NS3/4A protease inhibitor. It impairs the activity of a protein called NS3 that is used by HCV)
- Daclatasvir (a NS5A inhibitor. It impairs the protein NS5A, a protein that plays a role in hep C RNA replication)
- Beclabuvir (a non-nucleoside NS5B polymerase inhibitor. It impairs the protein NS5B)
Possible Daily Dose: 1 pill once or twice daily +/- ribavirin
SVR: 82 – 100%
Length of Treatment: 12 weeks or 24 weeks
Common Side Effects: Some people in clinical trials reported headache, diarrhea, fatigue, and/or nausea.
Sampling of Phase III Clinical Trial Results:
|Clinical Trial||Patients||Treatment Regimen||SVR12/24*|
|ALLY-3 (12 weeks)||GT 3 Treatment-naive||Daclatasvir + Sovaldi**||90%|
|GT 3 Treatment-experienced*** with compensated cirrhosis (except those who had already tried NS5A inhibitors)||86%|
|UNITY-1 (12 weeks)||GT 1 Treatment-naive without cirrhosis||GT 1a||Daclatasvir / Asunaprevir / Beclabuvir||90%|
|GT 1 Treatment-experienced without cirrhosis||GT 1a||Daclatasvir / Asunaprevir / Beclabuvir||85%|
|UNITY-2 (12 weeks)||GT 1 Treatment-naive with compensated cirrhosis||Daclatasvir / Asunaprevir / Beclabuvir + Ribavirin||98%|
|Daclatasvir / Asunaprevir / Beclabuvir||93%|
|GT 1 Treatment-experienced with compensated cirrhosis||Daclatasvir / Asunaprevir / Beclabuvir + Ribavirin||93%|
|Daclatasvir / Asunaprevir / Beclabuvir||87%|
|Collapsing these groups, 90% of all patients who received daclatasvir / asunaprevir / beclabuvir alone and 96% who used daclatasvir / asunaprevir / beclabuvir plus ribavirin were cured.|
|HALLMARK- Dual (24 weeks)||GT 1b Treatment-naive||Daclatasvir + Asunaprevir||90%|
|GT 1b Peginterferon/ribavirin non-responder||82%|
|GT 1b Peginterferon/ribavirin ineligible/intolerant||82%|
|GT 1b Cirrhotic||84%|
|GT 1b Non-cirrhotic||85%|
|*In clinical trials for hepatitis C virus (HCV) infection treatments, the goal is to cure/achieve SVR (sustained viral response)/reduce the virus so that it can’t be detected in the blood and liver disease from hep C is stopped. SVR12 or SVR24 means that the treatments can achieve this response after 12 or 24 weeks of therapy.
**Sovaldi is being developed by Gilead Science.
***Treatment-experienced means that the patients who took part in this trial had already unsuccessfully tried to cure their HCV with pegylated interferon (pegIFN)
Sampling of Phase III Clinical Trials Still Ongoing:
|Clinical Trial||Patients||Treatment Regimen||SVR12/24|
|ALLY-2 (12 weeks)||Any GT, HCV/HIV coinfection, Treatment-naive, Treatment-experienced||Daclatasvir + Sovaldi (once daily)||97% (high SVR regardless of treatment experience, GT, cirrhosis). No alteration of HIV meds required. Completion Date was Feb 2015.
|UNITY-3 (12 weeks)||GT 1b Treatment-naive non-cirrhotic||Daclatasvir / Asunaprevir / Beclabuvir||Estimated Study Completion Date: Sept 2015|
|ALLY-1 (12 weeks)||Any Genotype (GT), With cirrhosis who have already received a liver transplant||Daclatasvir + Sovaldi + Ribavirin||Estimated Study Completion Date: Oct 2015|
ClinicalTrials.gov lists additional clinical trials involving daclatasvir and asunaprevir. The website is pretty user-friendly.
Please keep an eye out for the coming patient input survey.