ALLY Trial Demonstrates 97% Hepatitis C Cure Rates Among Patients Coinfected with HIV After Ribavirin-Free Investigational 12-Week Regimen of Daclatasvir and Sofosbuvir

Daclatasvir-sofosbuvir 12-week regimen resulted in: 

• 96% hepatitis C cure rate among patients with HVC genotype 1 disease (n=80/83) 
• 100% hepatitis C cure rate among patients with HCV genotype 2, 3 and 4 disease (n=26/26) 

High HCV cure rates seen with no need to alter existing HIV medication regimens 

Thursday, February 26, 2015 3:15 pm EST

 

"The ALLY-2 results show that daclatasvir paired with sofosbuvir produced high cure rates in this trial regardless of the coinfected patients’ HCV genotype."

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced results from ALLY-2, a Phase III clinical trial evaluating the investigational once-daily combination of daclatasvir and sofosbuvir for the treatment of patients with chronic hepatitis C virus (HCV) coinfected with HIV – a patient population that historically has been challenging to treat in large part due to potential drug-drug interactions between the therapy regimens used to treat each infection.

“The results of ALLY-2 signal that nearly all HIV-HCV coinfected patients in the study could be cured of hepatitis C with a 12-week regimen on daclatasvir and sofosbuvir,” said David Wyles, M.D., ALLY-2 Lead Investigator and Associate Professor of Medicine in the Department of Medicine, Division of Infectious Diseases at the University of California San Diego. “The trial demonstrated the dosing flexibility afforded by the daclatasvir-sofosbuvir regimen did not require alteration of HIV medications because of potential drug-drug interactions. This is a paramount consideration for clinicians treating this patient population.”

Among ALLY-2 patients treated for 12 weeks (treatment-naïve and -experienced), 97% (n=149/153) achieved cure (sustained virologic response 12 weeks after treatment; SVR12). The study met the primary endpoint, with 96% (n=80/83) of treatment-naïve genotype 1 patients achieving SVR12. Treatment with daclatasvir in combination with sofosbuvir in this study showed high SVR rates, with no discontinuations due to adverse events, and no serious adverse events related to study medications throughout the treatment phase.

“While substantial strides have been made in the battle against hepatitis C, a significant number of patients with complicated disease and treatment histories need additional treatment options to help them achieve hepatitis C cure,” said Douglas Manion, M.D., head of Specialty Development, Bristol-Myers Squibb. “The ALLY-2 results show that daclatasvir paired with sofosbuvir produced high cure rates in this trial regardless of the coinfected patients’ HCV genotype.”

According to the Centers for Disease Control and Prevention (CDC), about one quarter of HIV-infected persons in the United States - approximately 300,000 people - are also infected with hepatitis C, and HCV infection progresses more rapidly to liver damage in people living with HIV.
In ALLY-2, high SVR rates occurred among all patients treated for 12 weeks, regardless of prior treatment experience, HCV genotype, cirrhosis status, concurrent combination antiretroviral therapy regimen, or race. African-American patients comprised 34% of study participants; in this patient demographic, SVR12 rates were 98% (n=49/50). ALLY-2 also included an 8-week arm; 38 of 50 treatment-naïve patients with HCV achieved SVR12. However, study investigators concluded that further studies are needed to assess the potential of shorter-duration, all-oral treatment regimens.
Additional safety data demonstrated a low rate of Grade 3/4 lab abnormalities in the study: INR (1%), AST (0.5%), Tbili (4%), Lipase (3%).
 
About ALLY-2: Study Design
This Phase III open-label clinical trial randomized 151 treatment-naïve and 52 treatment-experienced HCV (genotypes 1-4) patients coinfected with HIV-1 on a broad range of antiretroviral regimens, into 3 cohorts. Among treatment-naïve patients, one cohort received daclatasvir 30, 60, or 90 mg (dose adjusted for concomitant antiretroviral therapy) plus sofosbuvir 400 mg once daily for 12 weeks, and another received the same dosage and combination for 8 weeks.

The treatment-experienced cohort also received daclatasvir 30, 60, or 90 mg plus sofosbuvir 400 mg once daily for 12 weeks. Daclatasvir was dose-adjusted to accommodate concomitant antiretrovirals: 30 mg with ritonavir-boosted PIs, 90 mg with NNRTIs except rilpivirine. All cohorts had follow-up through post-treatment week 24. The primary endpoint was the SVR12 rate among genotype 1 treatment-naïve patients after 12 weeks of treatment. Patients with cirrhosis were permitted.
 

Read complete press release here:

PHOTON-2 Study Addresses Combination Hepatitis C Pill For HIV+ Patients

MedicalResearch.com Interview with:
Prof Jean-Michel Molina
Maladies Infectieuses et Tropicales, Hôpital
Saint-Louis, Paris France

Medical Research: What is the background for this study? What are the main findings?

Prof. Molina: Treatment of co-infected patients is complicated by drug drug interactions with HIV drugs, and the news DAAs are not very potent on HCV G2 and 3 infections.

Medical Research: What should clinicians and patients take away from your report?

Prof. Molina: The simple combination of sofosbuvir plus ribavirin (available as a generic drug) provides potent response rates above 80% for co-infected patients with all genotypes, with limited drug drug interactions with HIV drugs.

Read more...

Snapshots —Alan Franciscus, Editor-in-Chief

Abstract: Low Risk of Liver Decompensation among Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients with Mild Fibrosis in the Short-Term.
  Authors: J Macias et al.  Hepatology. 2014 Dec 24. doi: 10.1002/hep.27674. [Epub ahead of print]

Results and Conclusions: The authors of this study wanted to find out which HIV/HCV patients can safely wait, or wait in the short term for treatment.  This study was conducted during the time that pegylated interferon was part of the treatment regime.  A total of 1729 patients were evaluated (683 patients by liver biopsy; 1046 by liver stiffness measurement) and followed over time. The authors concluded that patients who did not have advanced fibrosis were at “very low risk” of decompensated cirrhosis, at least in the short term.  In this population, a careful watchful waiting is appropriate—in the author’s opinion.

Editorial Comments: I find this study interesting and valuable.  But I think it is a dangerous game to play.  This is a population of patients who typically have faster disease progression—faster than people who are monoinfected.  It may be safe if people are followed very carefully.  But wouldn’t it be easier and safer to treat now and not take the chance of putting people at undue risk?

Abstract: Hepatitis C Virus (HCV) Antibody Dynamics Following Acute HCV Infection and Reinfection among HIV-Infected Men Who Have Sex with Men.
  Authors:  J. Vanhommerig et al. Clin Infect Dis. 2014 Dec 15;59(12):1678-85. doi: 10.1093/cid/ciu695. Epub 2014 Sep 3.

Results and Conclusions: This study identified 63 HIV/HCV coinfected patients who had tested positive for HCV antibodies and HCV RNA (viral load).  The patients were followed for 4 years.  Five of the patients spontaneously cleared HCV and 31 of 43 patients were treated and cured.  In 36 (5 spontaneously cleared; 31 cured) the antibody titers (the measurements) declined.  In 8 of the 31 patients the HCV antibody titers disappeared. 

Eighteen of the patients were re-infected with a dif­ferent strain than the initial one and devel­oped a surge in both antibodies and HCV RNA.  The researchers believed that one patient was re-infected three separate times after the first successful treatment. 

Editorial Comments:  I couldn’t find the entire journal article to find out what type of counseling efforts were offered to the study participants.  This study, however, should remind us we need to educate people about prevention measures.  But what was interesting is that 8 people had undetectable antibody titers in this small study.  On a personal note, I did a demonstration of an HCV antibody test.  I was cured of hepatitis C more than 10 years ago.  The results showed very low reactive results.  I wonder if my antibody titers will become undetectable after time.  This study made me wonder how many ‘Baby Boomers’ became infected many years ago, naturally cleared the virus, and when tested recently had antibody titers too low to register.

http://hcvadvocate.org/news/newsLetter/2015/advocate0115_mid.html#3