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Gilead's Sofosbuvir (GS-7977), 100% SVR4 in treatment naive G1's

Nov 11, 2012 - 7 comments
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Hepatitis C



This has already been posted by Orphaned Hawk on the Hep C forum, but I thought it might be a good idea to post in my journals as well.  100% of treatment naive Hep C, G1 patients achieved SVR4 with Gilead's Sofosbuvir (GS-7977), combined with GS-5885 and Ribavirin, according to GS's announcement at the AASLD conference in Boston Nov, 2012.
Advocate1955
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AASLD-100 Percent Sustained Virologic Response Rate (SVR4) Interferon-Free Regimen of Sofosbuvir (GS-7977), GS-5885 and Ribavirin in Treatment-Na ïve Geno 1 Hepatitis C Infected Patients
Gilead Announces 100 Percent Sustained Virologic Response Rate (SVR4) for an Interferon-Free Regimen of Sofosbuvir (GS-7977), GS-5885 and Ribavirin in Treatment-Na ïve Genotype 1 Hepatitis C Infected Patients

- Phase 3 Study with a Fixed-Dose Combination Tablet of Sofosbuvir and GS-5885 Now Underway

BOSTON--(BUSINESS WIRE)--Nov. 10, 2012
Gilead Sciences (Nasdaq: GILD) today announced interim data from the ongoing Phase 2 ELECTRON study examining a 12-week course of therapy with the investigational nucleotide sofosbuvir (formerly referred to as GS-7977), the NS5A inhibitor GS-5885 and ribavirin in patients with genotype 1 chronic hepatitis C virus (HCV) infection. Among treatment-naïve patients receiving this combination, 100 percent (n=25/25) remained HCV RNA undetectable four weeks after completing therapy (SVR4). These data will be presented on Tuesday, November 13th at the 63rd annual meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2012) in Boston.
  
“These results indicate that adding GS-5885 to sofosbuvir-based regimens may enhance SVR rates, potentially offering HCV genotype 1 infected patients a convenient 12-week course of oral therapy,” said Professor Edward Gane, MD, Deputy Director and Hepatologist, New Zealand Liver Transplant Unit, Auckland City Hospital in New Zealand, and principal investigator of the ELECTRON study. “Along with other data from the ELECTRON study, these results add to the growing body of evidence supporting the potential for effective sofosbuvir-based all-oral regimens.”
  
Gilead recently initiated the first Phase 3 trial (ION-I) evaluating a fixed-dose combination of sofosbuvir and GS-5885 in treatment-naïve genotype 1 patients. This four-arm study is evaluating the fixed-dose combination with and without ribavirin for 12-and 24-week durations in 800 patients, 20 percent of whom have evidence of cirrhosis.
  
Data from five additional arms of the ELECTRON study examining sofosbuvir-based therapy in various patient populations also will be presented:
  

Treatment Population Results
Sofosbuvir + ribavirin for 12 weeks GT 1 treatment-naïve 84% (21/25) SVR12
GT 1 null responders 10% (1/10) SVR12
GT 2/3 treatment-experienced 68% (17/25) SVR12
Sofosbuvir + ribavirin for 8 weeks GT 2/3 treatment-naïve 64% (16/25) SVR12
Sofosbuvir + ribavirin (800 mg) for 12 weeks GT 2/3 treatment-naïve 60% (6/10) SVR8


Preliminary data from a subset of an ongoing cohort in the ELECTRON study in which nine genotype 1 previous null responders were treated with sofosbuvir, GS-5885 and ribavirin for 12 weeks also will be presented on Tuesday. Thus far, three of the nine patients have reached the four-week post-treatment time point and all three remain HCV negative.
  
Both sofosbuvir in combination with ribavirin and sofosbuvir in combination with GS-5885 and ribavirin were well tolerated in the ELECTRON study. In the sofosbuvir combined with GS-5885 and ribavirin groups, there was one discontinuation due to an adverse event unrelated to study drugs. Despite stopping therapy at week 8, this patient also achieved SVR4.
  
The most common adverse events were headache, fatigue, upper respiratory tract infection and nausea. The most common clinically significant grade 3/4 laboratory abnormality was a hemoglobin reduction.
  
Additional Safety Data for GS-5885
In a poster presentation at The Liver Meeting on Sunday, November 11th, investigators will report combined safety data for more than 1,000 patients who have received at least one dose of GS-5885, in combination with other HCV medicines, in six ongoing Phase 2 clinical trials. In this analysis, 616 patients received a 30 mg dose and 423 patients received the 90 mg dose of GS-5885, which is being assessed in Phase 3 research. More than 700 patients completed at least 12 weeks of treatment with GS-5885. Approximately 70 percent of patients were treatment-naïve and 70 percent had HCV genotype 1a infection.
  
Researchers concluded that GS-5885 is safe and well tolerated. No laboratory abnormalities or other safety signal of concern has been observed in the GS-5885 development program.
Sofosbuvir and GS-5885 are investigational products and their safety and efficacy have not yet been established.
  
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.
  
Forward-Looking Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the possibility that the proportion of patients who maintain a sustained virologic response 12 weeks post-treatment will not be as favorable as the sustained virologic response rates reported in this press release, the possibility that results from the arm of the ELECTRON study evaluating the efficacy and safety of sofosbuvir, GS-5885 and ribavirin in genotype 1 previous null responder patients will not be favorable once four and 12 week post-treatment data from all nine patients are available and the possibility of unfavorable results from additional arms of the ELECTRON study and subsequent clinical trials involving sofosbuvir and GS-5885 with and without ribavirin. As a result, sofosbuvir and GS-5885 as single agents or as a fixed-dose combination may never be successfully commercialized. Further, Gilead may make a strategic decision to discontinue development of the compounds or the fixed-dose combination regimen if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Annual Report on Form 10-K for the quarter ended September 30, 2012, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
  
For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

Source: Gilead Sciences, Inc.
Gilead Sciences, Inc.
Patrick O’Brien, 650-522-1936
Investors
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Cara Miller, 650-522-1616
Media

Related-UPDATE2: Abbott, Gilead impress with upbeat results for oral hep C drugs

Gilead posts positive results in mid-stage Hepatitis C study

(Reuters) - Gilead Sciences Inc on Saturday reported a 100 percent cure rate using a combination of drugs in a small number of patients with the most common and hardest to treat form of hepatitis C.
Rival Abbott Laboratories Inc, meanwhile, said a trio of its oral medicines to treat hepatitis C produced unprecedented cure rates in a larger number of patients who had failed to benefit from standard treatment, as well as very high cure rates for newly treated patients.

Data from both companies' mid-stage trials were released Saturday at the annual meeting of the American Association for the Study of Liver Disease in Boston.

Gilead's study, dubbed Electron, examined 25 patients with genotype 1 chronic hepatitis C virus (HCV) infection who were treated for 12 weeks with a combination of three drugs: sofosbuvir, ribavirin and GS-5885.

GS-5885 is from a promising new class of drugs known as NS5A inhibitors, which prevent the hepatitis C virus from replicating.

The infection was undetectable four weeks after completing therapy in all of the patients who had never received this combination of drugs before, Gilead said.

The drugs generally were well tolerated in the study, Gilead said.

In the sofosbuvir combined with GS-5885 and ribavirin patient groups, one patient dropped out because of an adverse side effect that the company said was unrelated to the drugs.
Sofosbuvir and GS-5885 are still being studied for their safety and efficacy.

The biopharmaceutical company will present the data on Tuesday at the annual meeting of the American Association for the Study of Liver Diseases in Boston.

Mark Schoenebaum, a biotech analyst with ISI Group, said in a research note that he expects Gilead shares to rise on Monday based on these "best case" results.

UBS analyst Matthew Roden said "these data strongly support Gilead's leadership position" in the hepatitis C virus space.

Gilead recently started the first Phase 3 trial evaluating a fixed-dose combination of sofosbuvir and GS-5885 in patients with genotype 1 chronic hepatitis C virus infection who had not received these drugs before.

This study is evaluating the fixed-dose combination with and without ribavirin for 12- and 24-weeks in 800 patients, 20 percent of whom have evidence of cirrhosis, or liver scarring.




Comments
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317787 tn?1473358451
by Dee1956, Jun 10, 2013
Thanks for all of this information, does SVR4 mean they are SVR as it used to be called 6 months after tx?  Just trying to understand it.
Thank you

Avatar universal
by Advocate1955, Jun 10, 2013
Hi Dee,
I will have to look it up and research further, but in the trials I think SVR4 means clear 4 weeks after EOT.
Advocate1955

3211536 tn?1359385569
by creewoman, Jun 12, 2013
Maybe this can help us really sick folks!

446474 tn?1446347682
by HectorSF, Jun 12, 2013
SVR4 is measuring viral load at four weeks after end of treatment. It is not used any longer because some patients relapsed after 4 weeks. SVR 12 is the standard duration to measure SVR when using Sofosbuvir.

The posted above trials are very early in the testing of Sofosbuvir. There is much more data about Sofosbuvir and its treatment available now that we have the data sets from a number of phase 3 trials. It was data from these newer trials (listed below) that was used in Gilead's filing with the FDA (NDA) for use of Sofosbuvir in treating hepatitis C that probably be approved by the FDA and then available on the market in early 2014.

"In the four trials, sofosbuvir was administered to nearly 1,000 patients with chronic HCV infection as part of an all-oral 12-week or 16-week treatment regimen in combination with ribavirin (RBV) in genotypes 2 and 3,
or with RBV and Pegylated interferon (peg-IFN) for 12 weeks in genotypes 1, 4, 5 and 6. Overall SVR12 rates (sustained viral response 12 weeks after completing therapy) from 50 to 90 percent were observed. Patients who achieve SVR12 are considered cured of their HCV infection."

NEUTRINO  - Genotype 1/4/5/6 TREATMENT-NAIVE only - Sofosbuvir + RBV + Peg-IFN for 12 weeks - 90%

FISSION -  g 2/3, treatment naive - sofosbuvir + RBV for 12 wks (67% SVR12) or Peg-IFN + RBV for 24 wks (67%)
POSITRON - g 2/3 - IFN intolerant, ineligible, or unwilling - sofosbuvir + RBV for 12 wks (78%) or placebo  (0%).
FUSION - g 2/3 treatment-EXP - sofosbuvir + RBV for 12 wks (50% SVR12) or sofosbuvir + RBV for 16 wks (73%).

NOTE: Contrary to many postings on Medhelp... There is NO all oral treatment (non-interferon treatment) for genotypes 1, 4, 5 and 6. Treatment is ONLY for TREATMENT-NAIVE patients. Not for patients that have treated before.
All oral treatment for genotype 1 patients is hoped to be Sofosbuvir + Ledipasvir (FDC) with or without RBV that may be available in 2015.

"On April 8, Gilead submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for sofosbuvir for the treatment of HCV infection. The data submitted in the NDA support the use of sofosbuvir and RBV as an all-oral therapy for patients with genotype 2 and 3 HCV infection, and for sofosbuvir in combination with RBV and peg-IFN for treatment-naïve patients with genotype 1, 4, 5 and 6 HCV infection."

- See more at: http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=1809511&highlight=#sthash.hducLqIR.dpuf"

Hector
Currently on week 40 of Sofosbuvir (400mg) + Ribavirin (1,200mg). Undetectable since week 2.

317787 tn?1473358451
by Dee1956, Jun 12, 2013
Dear H, thank you so much, I was getting confused and feeling way behind the times if someone could be SVR after 4 weeks, gosh even 12 weeks, that is like magic

So happy you are UND!

Avatar universal
by Geshmit, Jun 12, 2013
Hi there guys

I am doing Gilead's ION-1 trial in London, UK - geno 1, treatment naive: 12 week arm of sofosbuvir + ledispasvir with ribavirin - still waiting for week 4 (NOT post treatment but week 4 in treatment) viral load results -

But I am not as optimistic as I was at the start of treatment when I saw everything as rosy with a very high potential success rate. I now know that the early data was premature....so far in week 2 of treatment my viral load was 27 (down from 5 million) but I was hearing about people being undetectable in the 2nd week.

Does anyone know about our chances of this treatment for treatment naive genotype 1 patients? Perhaps not quite as rosy as I once thought.

Great that you are UND so far, Hector.

all the best to all

RainaM

317787 tn?1473358451
by Dee1956, Jul 07, 2013
This is all interesting, thank you for sharing, Raina, you might want to ask your question in the HCV Forum
Hang in there, your results are very impressive.

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