GUT: Vitamin B12 may improve SVR rates in HCV infected patients...

Study posted 7/18/12 via the journal GUT.  Researchers in Italy find a link between 5000 ug every 4 weeks of vitamin B12 and improved SVR... especially in the more difficult-to-treat genotype 1 patients with high baseline viral loads.  Researchers noted a 34% improvement in SVR in the arms containing B12 than in the arms that didn't. That's pretty cool in my book, but let's do a gut check all the same. OK, it's a small study, it's European (which means the patients have a higher probability of being Caucasian, lower BMI, CC alelle, genotype 1b, all that stuff that makes these patients more likely to respond to traditional pegylated interferon + ribavirin therapy than patient types over here in the States) but hey!! Vitamin B12 can be had on the cheap! Further prospective and larger clinical trials will have to be done to confirm or deny the seemingly extra added boost to SVR rates, especially with the new standard of care. Let's hope it's not another silymarin experience.

GUT
Vitamin B12 supplements may help treat hepatitis C

Safe and inexpensive option for boosting response rate to antiviral drugs

[Vitamin B12 supplementation improves the rate of sustained viral response in patients chronically infected with hepatitis C virus Online First doi 10.1136/gutjnl-2012-302344]

Adding vitamin B12 to standard hepatitis C virus (HCV) treatment significantly boosts the body’s ability to keep the virus at bay, indicates a pilot study published online in the journal Gut.

The effects were particularly strong in patients whose infection was proving difficult to treat effectively, the findings showed.

Between 60% and 80% of those infected with the viral liver infection HCV will go on to develop chronic hepatitis, and roughly a third of them will progress to cirrhosis and terminal liver disease.

Standard treatment of interferon (peg IFN) and ribavarin clears the virus in about 50% of patients infected with genotype 1 HCV and 80% of those infected with genotypes 2 or 3.   But this approach fails to clear the virus in around half of all those infected with HCV or the infection returns once treatment stops.  

While trials of new generation antiviral drugs show promise, they are expensive, and can make treatment more difficult. And questions still remain about how well they will work in practice, say the authors.

Experimental research dating back a decade suggests that vitamin B12 may have a role in suppressing HCV. The liver is the body’s primary storage centre for vitamin B12, but this capacity is impaired by diseases directly affecting the organ. The researchers therefore wanted to see if adding vitamin B12 to standard treatment would make a difference.

Ninety four patients with HCV infection were randomly allocated to receive standard treatment or standard treatment plus vitamin B12 (5000 ug every 4 weeks) for between 24 (genotypes 2 and 3) and 48 weeks (genotype 1).

The body’s ability to clear the virus was assessed after 4 weeks (rapid viral response), after 12 weeks (complete early viral response), at the end of treatment and at 24 weeks after stopping treatment (sustained viral response).

There was no difference between the two treatment approaches at 4 weeks, but there were significant differences in response at all the other time points, particularly 24 weeks after stopping treatment, which is the aim of HCV treatment and the closest it can be get to a cure.  

The effects were also significantly greater among those who carried the type 1 strain, which is particularly hard to treat, and those high levels of infection (high viral load) to begin with.

Overall, adding vitamin B12 to standard therapy strengthened the rate of sustained viral response by 34%, the findings showed.

The authors conclude that until clear eligibility criteria for treatment with the new generation antiviral drugs are established, standard treatment plus vitamin B12 is a safe and inexpensive alternative, particularly for those who carry a strain of the virus that is hard to treat.

They add: “This strategy would be especially useful in those countries where, owing to limited economic means, the new generation antiviral therapies cannot be given in routine practice.”

Pharmasset Initiates Phase 1b Multiple Ascending Dose Clinical Trial of PSI-938 in Patients with Chronic Hepatitis C

-- PSI-938 single ascending dose study in healthy volunteers supports progression to 7 day monotherapy study in HCV infected patients -- PSI-938 was generally safe and well tolerated with no dose-limiting toxicity -- Further results from single ascending and multiple ascending dose trials are expected in the third quarter 2010

PRINCETON, N.J., July 28 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (NASDAQ:VRUS) announced today that safety and pharmacokinetic data from the PSI-352938 ("PSI-938") single ascending dose study support progression to a multiple ascending dose trial with PSI-938, which has initiated dosing. PSI-938 is a guanine nucleotide analog polymerase inhibitor for the treatment of chronic hepatitis C virus (HCV) infection. This study is designed to assess the safety, tolerability and antiviral activity of PSI-938 monotherapy administered over 7 days in HCV-infected individuals.
 

"PSI-938 is the third differentiated nucleoside analog that Pharmasset has advanced into clinical development for HCV," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "As with RG7128 and PSI-7977, PSI-938 demonstrates a high barrier to resistance in vitro; but unlike the cytidine and uridine analogs, PSI-938 retains equivalent potency against the S282T mutant. As the HCV field moves toward IFN-sparing, all-oral DAA combinations, we continue to believe nucleosides could become the backbone of care given these differentiating attributes and have the potential to be combined with all DAA classes."
 

PSI-938 Phase 1 Program Overview
 

The Phase 1 program is investigating the safety, tolerability and pharmacokinetics of PSI-938 in healthy subjects following escalating single doses (Phase 1a), and in patients chronically infected with HCV genotype 1 following repeat dosing for 7 days (Phase 1b). The Phase 1b study will additionally investigate hepatitis C viral dynamics and monitor for the development of drug resistance.
 

Subjects in the Phase 1a single ascending dose study received single doses of PSI-938 ranging from 100 mg to 800 mg or a matching placebo. Preliminary data from the phase 1a single ascending dose study includes:
 

--  No serious adverse events or discontinuations;
  --  No dose-related adverse events or dose-limiting toxicity;
  --  No grade III / IV lab abnormalities;
  --  No clinically significant changes in vital signs or ECGs; and
  --  PK which supports QD dosing.

A Phase 1b multiple ascending dose trial has now been initiated in treatment-naïve patients with chronic HCV genotype 1 infection. Subjects will be enrolled at multiple centers in the US and randomized to PSI-938 or placebo. Based upon the results from the first time in human study, the first dose of PSI-938 to be tested will be 100 mg administered once daily. The primary objectives of this study are to assess the safety, tolerability, pharmacokinetics and viral dynamics of PSI-938 after repeat dosing over 7 days.
 

  Results from both studies are expected in the third quarter of 2010.

  Purine and Pyrimidine Analogs

Pharmasset's purine nucleoside/tide analogs share many of the benefits of pyrimidine nucleoside/tide analogs, such as RG7128 and PSI-7977, in that they have demonstrated in vitro activity across multiple HCV genotypes, have a higher barrier to resistance than other classes of HCV small molecules in development, and, in spite of the prodrug technology, have no CYP 3A4 liability and thus a lower risk of drug interactions when combined with other direct acting antivirals targeting HCV. In addition, Pharmasset's purine analogs retain equivalent potency against wild type HCV and virus with the S282T mutation associated with in vitro resistance in other nucleoside/tide analogs in development. Furthermore, the purines are metabolized to the active triphosphate form through a different phosphorylation pathway than the pyrimidine analogs, thus decreasing the risk of competition between the two analogs for conversion to the active triphosphate. Given these characteristics, Pharmasset's purine and pyrimidine analogs have the potential to be combined as part of a future treatment regimen, which will be the focus of upcoming trials.