In a press release from Achillion Pharmaceuticals, Inc., the Phase 2a study results were announced. The goal of the study was to understand the safety and to determine an effective dose of the combination of odalasvir, AL-335 with and without simeprevir to treat HCV genotype 1 treatment-naïve patients. Listed in the table below are the results.
|400 mg QD||50 mg QD||100 mg QD||8 weeks||100% (20 of 20 pts)|
|800 mg QD||50 mg QOD||none||8 weeks||90% (18 of 20 pts)|
|800 mg QD||50 mg QOD||75 mg QD||8 weeks||100% (20 of 20 pts)|
|800 mg QD||50 mg QOD||75 mg QD||6 weeks||100% (20 of 20 pts)|
The combination of drugs was safe and well-tolerated. The most common side effects were headache, fatigue and an upper respiratory tract infection. There was one serious adverse event that resolved when treatment ended. Based on the results of this trial, the combination of odalasvir (25mg), AL-335 (800 mg), and simeprevir (75 mg) is being advanced into Phase 2b studies. The clinical development of these drugs will eventually be expanded to treat genotypes 1, 2, 3, 4, 5 and 6. The clinical trials identifier is NCT02765490 on www.clinicaltrials.gov. The trial is listed as active, but it is not currently recruiting patients. When it becomes active it will be listed on HCV Advocate Clinical Trials Reference Guide – http://hcvclinical.hcvadvocate.org/
The difficult task is to achieve a 100% cure rate with a short treatment duration when and if it enters into Phase 3 clinical trials.
Is this the new blockbuster HCV therapy? The bar now is set so high that an HCV drug has to have high cure rates, low side effects and have ease of use. The cost of a new drug is another important factor to bring a blockbuster HCV drug to market.
Still, we need more HCV medications to treat hepatitis C, so that people living with hepatitis C have more treatment choices. I’m pulling for this combination to make it!
Source: Achillion Press Release
3-Week Response-Guided Therapy
An important study was recently published in Lancet Gastroenterology & Hepatology. The study—Efficacy and safety of 3-week response-guided Triple direct-acting antiviral therapy for chronic hepatitis C: a phase 2, open-label, proof-of-concept study—holds the promise of changing the way that people with hepatitis C are treated.
The study evaluated a 3-week treatment duration of a combination of HCV medications. Patients were enrolled between April 05, 2015 and April 15, 2015. All of the 26 patients enrolled in the study were HCV genotype 1b treatment naïve without cirrhosis. The patients were randomly assigned to three treatment groups.
- Twelve patients were treated with sofosbuvir, ledipasvir and asunaprevir;
- Six patients were treated with sofosbuvir, daclatasvir and simeprevir;
- Eight patients were treated with sofosbuvir, daclatasvir and asunaprevir.
Note: Ultrarapid virological response is defined as less than 500 IU/mL HCV RNA or viral load at day 2 of treatment.
Six patients in each group achieved an ultrarapid virological response. Patients who achieved an ultrarapid virological response were continued on their current medications for a total of 3 weeks.
The patients who did not achieve an ultrarapid virological response by day 2 were switched to sofosbuvir plus ledipasvir for either 8 or 12 weeks.
All of the patients who achieved the ultrarapid virological response who received 3 weeks of treatment were cured. The patients are still being followed and as of March 2016 there has not been any adverse events or treatment-related relapse.
The most common side effects in all of the 3-week patient groups were fatigue and headache. There were no serious side effects.
This was presented at the Liver Conference 2015, but little information was provided. Now that it is published in a prestigious journal—The Lancet—it provides more information and credibility. The current group of scientists is planning a larger study in Mongolia. I hope this approach is being studied elsewhere including the United States. It could have the potential to reduce the treatment duration, lower the side effects, improve drug adherence and greatly reduce the cost of therapy.
A couple of caveats:
- Genotype 1b is one of the easiest genotypes/subtypes to cure. This approach—or a similar approach—needs to be studied in other genotypes/subtypes.
- This is a small proof of concept clinical trial. There is a need for larger studies with a diverse patient population.
Source: Efficacy and safety of 3-week response-guided triple direct-acting antiviral therapy for chronic hepatitis C infection: a phase 2, open-label, proof-of-concept study—G Lau et al. Volume 1, Issue 2, October 2016, Pages 97–104Share!