Simeprevir & sofosbuvir demonstrates good early cure rate with or without ribavirin

Simeprevir & sofosbuvir demonstrates good early cure rate with or without ribavirin

Liz Highleyman

Produced in collaboration with hivandhepatitis.com

 

An all-oral combination of simeprevir plus sofosbuvir, with or without ribavirin, led to an early cure for most hard-to-treat prior null responders with genotype 1 hepatitis C studied in the phase 2a COSMOS trial, according to a presentation last week at the 20^th Conference on Retroviruses and Opportunistic Infections (CROI 2013) in Atlanta.

The advent of direct-acting antiviral agents has brought about a new era of treatment for chronic hepatitis C virus (HCV) infection. Several new drug candidates have been shown to increase effectiveness when added to pegylated interferon and ribavirin, but many people with hepatitis C and their clinicians are awaiting regimens that omit interferon and its difficult side-effects.

Eric Lawitz from Alamo Medical Research in Texas presented interim findings from an open-label, exploratory phase 2a study looking at all-oral regimens containing simeprevir (formerly TMC435), a NS3/4A protease inhibitor being jointly developed by Janssen and Medivir, plus Gilead Sciences' NS5B polymerase inhibitor sofosbuvir (formerly GS-7977), with or without ribavirin.

Read more..........

View abstract 155LB on the conference website.

A webcast of the session in which this research was presented, Advances in ARV and Anti-Hepatitis C Virus Therapy, is available on the conference website.

 

Faldaprevir ups interferon response in HIV/HCV co-infection

Faldaprevir ups interferon response in HIV/HCV co-infection

Liz Highleyman

Produced in collaboration with hivandhepatitis.com

 

Adding the hepatitis C virus (HCV) protease inhibitor faldaprevir (formerly BI 201335) to pegylated interferon and ribavirin led to a higher early response rate and the potential for shorter treatment for HIV/HCV co-infected people, according to a presentation last week at the 20^th Conference on Retroviruses and Opportunistic Infections (CROI 2013) in Atlanta.

Direct-acting antiviral agents that target different steps of the HCV lifecycle have ushered in a new era of treatment. While interferon-free, all-oral regimens are on the horizon, many people with chronic hepatitis C have advancing liver disease and cannot wait. Although HIV-positive people with hepatitis C experience more rapid liver disease progression, they will have to wait longer for approval of interferon-free combinations, as new agents are typically approved for HCV monoinfected people first.

Read more........

View abstract 40LB on the conference website.

A webcast of the session in which this research was presented, Advances in Hepatitis Therapy, is available on the conference website.

Interferon-free regimen cures 100% of hard-to-treat hepatitis C

Related: Conference on Retroviruses and Opportunistic Infections.

Coverage @ MedPage Today
Ledipasvir (GS-5885), Extra Drug Hikes HCV Regimen's Efficacy
All-Oral Regimens Work in HCV

Coverage @ NATAP
CROI: 20th Conference on Retroviruses and Opportunistic Infections

Interferon-free regimen cures 100% of hard-to-treat hepatitis C

By: PATRICE WENDLING, Internal Medicine News Digital Network

ATLANTA – Adding ledipasvir to sofosbuvir and ribavirin produced sustained virological responses 12 weeks after therapy in 100% of treatment-naive and prior nonresponder patients with chronic hepatitis C genotype 1 in the ELECTRON trial.

"Certainly adding a second direct-acting antiviral agent, ledipasvir, increases the efficacy of sofosbuvir plus ribavirin," Dr. Edward Gane said at the Conference on Retroviruses and Opportunistic Infections.

Three-quarters of the roughly 170 million people infected with hepatitis C virus (HCV) worldwide have genotype 1, the most difficult strain to treat.

Current treatment includes triple therapy with a protease inhibitor plus peginterferon and ribavirin for 24-48 weeks, but PI-based therapy is limited by complex dosing regimens, the potential for resistance, and lower responses in prior nonresponders, explained Dr. Gane of Auckland Clinical Studies in New Zealand.

The investigators hypothesized that combining two direct-acting antivirals with a different mechanism would enhance response.

At last year’s CROI meeting, Dr. Gane reported that treatment with the nucleotide NS5B inhibitor sofosbuvir (formerly known as GS-7977) and ribavirin alone led to early viral load suppression, but relapses within 4 weeks of stopping treatment resulted in 12-week posttreatment sustained virological response (SVR12) rates of 84% among treatment-naive patients and only 10% among previous interferon-based therapy null responders.

In the current arm of the trial, the NS5A inhibitor ledipasvir (formerly known as GS-5885) was added to sofosbuvir and weight-based ribavirin, all for 12 weeks, in 25 noncirrhotic treatment-naive and 9 null responders, defined by less than a 2-log reduction in HCV RNA after 12 weeks of peginterferon and ribavirin.

The majority of treatment-naive and null responders were genotype 1a (80% and 89%) and had high baseline HCV RNA loads (mean 5.9 log₁₀ IU/mL and 6.9 log₁₀ IU/mL). The more favorable IL28B genotype CC genotype was present in 36% of treatment-naive patients, but in no null responders. The patients median age was 48; 94% were white.

Early on–treatment viral suppression was very rapid, with all treatment-naive patients and all but one prior null responder having an undetectable viral load at week 4, Dr. Gane said. This patient’s load was on the threshold at week 4 and became undetectable by week 5, resulting in SVR12 rates of 100% in both groups.

No viral breakthroughs were observed, and all patients achieved an end-of-treatment response.

Unlike the earlier arm of the trial, however, both groups maintained undetectable HCV viral loads at 4 and 12 weeks after therapy, he said.

The triple combination was well tolerated and safe. Three serious adverse events occurred, but none were treatment related. One patient had to stop therapy at week 8 due to the event, but subsequently achieved SVR24. The most common adverse events were anemia (20%), depression (8%), and headache (4%), and all were in treatment-naive patients.

Grade 3 laboratory abnormalities occurred in 52% of the treatment-naive and 22% of null responders. No grade 4 abnormalities were seen, Dr. Gane said.

Ledipasvir and sofosbuvir have been combined into a single fixed-dose tablet and is being evaluated in phase III studies in patients with cirrhosis and to determine whether there is a need for ribavirin, he said. Additional studies are also underway to explore shorter durations of therapy.

 

ELECTRON was sponsored by Gilead Sciences. Dr. Gane reported ties with Gilead, Janssen-Cilag, Novartis, Pharmasset, Roche and Vertex.

 

 http://www.internalmedicinenews.com/single-view/interferon-free-regimen-cures-100-of-hard-to-treat-hepatitis-c/9f0cb4962f5ecfd36e108db75c6496f9.html

20th Conference on Retroviruses and Opportunistic Infections

Conference Reports for NATAP

20th Conference on Retroviruses and
Opportunistic Infections
Atlanta GA
March 3 - 6, 2013

SVR4 results of a once daily regimen of simeprevir (TMC435) plus sofosbuvir (GS-7977) with or without ribavirin in HCV genotype 1 null responders - (03/06/13)

Similar Cognition Outcomes After 24 Weeks for Tenofovir/FTC + Atazanavir/r (ATV/r)-Experienced HIV+ Subjects or Those Simplifying to Abacavir/3TC+ATV - (03/06/13)

High Efficacy of Sofosbuvir in Combination with Weight Based Ribavirin for 24 weeks in Difficult to Treat HCV Infected Genotype-1 Patients - (03/06/13)

Distribution and Antiviral Activity in Cerebrospinal Fluid (CSF) of the Integrase Inhibitor, Dolutegravir (DTG): ING116070 Week 16 Results - (03/06/13)

Dolutegravir (DTG) Versus Raltegravir (RAL) in ART-Experienced, Integrase-Naive Subjects: 24-Week Interim Results From SAILING (ING111762) - (03/06/13)

Baby Cure at CROI - (03/06/13)

NRTI-Sparing Second-Line Regimen Holds Its Own in Randomized Trial - written by Mark Mascolini - (03/06/13)

Peak Bone Mass Lower in Young HIV+ vs HIV- Men--and Bone Structure Abnormal - written by Mark Mascolini - (03/06/13)

Dolutegravir Superior to Raltegravir in ART-Experienced Integrase Inhibitor Naive at 24 Weeks - written by Mark Mascolini - (03/06/13)

Wide US Study Finds 16% With Newly Diagnosed HIV Carry Resistant Virus - written by Mark Mascolini - (03/06/13)

Safety and Antiviral Activity of MK-1439, a Novel Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), In Treatment-Naïve HIV-Infected Patients - (03/05/13)

Seven-Day Monotherapy With New NNRTI Yields Sharp Viral Load Drop - written by Mark Mascolini - (03/05/13)

Smoking Rate Twice Higher With Than Without HIV in First National US Study - written by Mark Mascolini - (03/05/13)

Long-Term Efavirenz Linked to Worse Neurocognitive Function in US CHARTER Group - written by Mark Mascolini - (03/05/13)

Coronary Artery Danger Signals More Common in Young HIV+ Men Than HIV- Men - written by Mark Mascolini - (03/05/13)

Comparative Study of Tenofovir Alafenamide vs Tenofovir Disoproxil Fumarate, Each with Elvitegravir, Cobicistat, and Emtricitabine, for HIV Treatment - (03/05/13)

New tenofovir prodrug virologically equivalent to TDF--and easier on kidneys and bone - written by Mark Mascolini - (03/05/13)

Protective Effect of HBV-active c-ART against primary HBV-Infection - (03/05/13)

Age Raises Rate of Dangerous Coronary Artery Plaques in HIV+ But Not HIV- MACS Men - written by Mark Mascolini - (03/05/13)

Higher MI, ESRD, Cancer Rates With HIV--But Not Necessarily at Younger Age - written by Mark Mascolini - (03/05/13)

Age Raises Rate of Dangerous Coronary Artery Plaques in HIV+ But Not HIV- MACS Men - written by Mark Mascolini - (03/05/13)

First interim results from a phase IIa study evaluating an all-oral regimen of Simeprevir and Sofosbuvir in prior null responder Hepatitis C patients - press release - (03/04/13)

Was An Infant Cured Of HIV? - (03/04/13)

For First Time, Baby Is Cured of H.I.V., Doctors Say - (03/04/13)

Long-Acting Integrase Inhibitor Shields Macaques From Anal Simian HIV - written by Mark Mascolini - (03/04/13)


HIV Prevention Fails in All Three VOICE Arms, as Daily Truvada PrEP Falls - written by Mark Mascolini - (03/04/13)

"Functional Cure" of HIV Claimed for Baby Treated 30 Hours After Birth - written by Mark Mascolini - (03/04/13)

ELECTRON: 100% SVR Rate for Once-Daily Sofosbuvir Plus Ledipasvir Plus Ribavirin Given for 12 Weeks in Treatment-Naïve and Previously Treated Patients With HCV GT 1 - (03/04/13)

RISK OF VIROLOGIC RELAPSE IN HEPATITIS C, GENOTYPE 1-INFECTED SUBJECTS AFTER 8, 12, OR 24 WEEKS OF TREATMENT WITH ABT-450/r + ABT-267 + ABT-333 + RBV: IDENTIFYING OPTIMAL TREATMENT DURATION - (03/04/13)

12 WEEKS OF ABT-450/r, NON-NUCLEOSIDE INHIBITOR AND RBV ACHIEVED SVR24 IN >90% OF TREATMENT-NAIVE HCV GT1 PATIENTS AND 47% OF PRIOR NONRESPONDERS - (03/04/13)

Pharmacokinetic interactions of darunavir/ritonavir, efavirenz, and tenofovir with the HCV protease inhibitor faldaprevir in healthy volunteers - (03/04/13)

STARTVerso 4: High rates of early virologic response in HCV genotype 1/HIV-co-infected patients treated with faldaprevir plus pegIFN and RBV - (03/04/13)

Boerhinger Ingelheim Announes Interim Results Evaluating Virologic Response Rates in HCV/HIV Coinfected Patients Treated with HCV Protease BI201335, and Drug Drug Interaction Studies with HIV ARTs - (03/04/13)