Sunday, May 15, 2011

VICTRELIS/Boceprevir FDA Approved:Now What? A Guide For Patients

VICTRELIS™ / Boceprevir FDA Approved: Now What ? A Guide For Patients

Friday the FDA approved VICTRELIS™ ( Boceprevir) for the treatment of Hepatitis C.
The HCV community has waited 20 years for a new drug and this drug will particularly give patients who treated unsuccessfully another shot at eliminating the virus.

In a format that is easy to understand I hope to cover the "need to know" facts on boceprevir, which Merck has  made available in the newly released Prescribing Information and Medication Guide .

Individuals who are contemplating treatment, and especially for those newly diagnosed may find the information in these guides overpowering. Living with this disease, being diagnosed or entering into the HCV medical maze is overwhelming enough, and today I hope to elevate some of that extreme anxiety. I remember my own journey treating this disease and all that goes hand in hand with either educating yourself on HCV or starting treatment. These new drugs have taken on a life of their own folks, with the newly FDA approved drug.....drum roll please........" Boceprevir " learning the protocol is a little complex but no doubt essential.

As a side note; I treated back in 2000 successfully and remain SVR today. This blog is here to provide patient to patient information. I understand the fear of  being diagnosed and the apprehension of starting therapy. In the coming weeks  valuable information on boceprevir will be coming to you from professionals via the media, the information will be added to the blog as it is published. I have no credentials, but what I do have is enthusiasm, and an enormous passion to help "you" understand this disease and how to treat it.

Need To Know Information
Merck said that it will begin the shipping of Victrelis to pharmacies within a week so that patients will have access to this new medication as soon as possible.

Separately, Merck will also add Victrelis to its patient assistance program through which eligible patients may be able to receive product free of charge.

VICTRELIS have not been studied in patients with decompensated cirrhosis, (HIV)-Co-Infection-trials ongoing,(HBV) Co-Infection, in liver or other organ transplant recipients or in (prior null responders). 

Studies indicate boceprevir is somewhat less effective than Vertex Pharmaceutical's telaprevir
The cure rate for new patients taking telaprevir ranged between 75 and 79 percent, compared with 60 and 65 percent for boceprevir.

Before you take VICTRELIS/boceprevir, tell your healthcare provider if you:

• have certain blood disorders such as anemia (low red blood cell count).
• have liver problems other than hepatitis C infection.
• have human immunodeficiency virus (HIV) or any other immunity problems.
• have had an organ transplant.
• plan to have surgery.
• have any other medical condition.
• are breastfeeding
Do not take VICTRELIS if you:

• take certain medicines. VICTRELIS may cause serious side effects when taken with certain medicines. Read the section "What should I tell my healthcare provider before taking VICTRELIS?"

Talk to your healthcare provider about anitdepressants before starting therapy.
Depression May Complicate Hepatitis C Therapy
We begin, available for viewing on the website is VICTRELIS™- Boceprevir: Prescribing Information and Medication Guide . Relevant information from these inserts/guides will be highlighted through out this blog entry.
The Doctor Is In
The importance of finding a physician who specializes in treating hepatitis C and who is familiar with these new drugs is at the forefront. After going over this blog entry you will be prepared for your first consultation, armed with detailed notes, and hopefully take an active role in your treatment regimen.
Related; Hepatitis C New Drugs:Telaprevir,Boceprevir Potential for Misuse Is ‘Huge’
What Is A Hepatologist ? What Is A Gastroenterologist?

Be Prepared;
Advice from Dr. Joe Galati
Obtain all of your old medical records from past treatment courses.
If you had prior liver biopsies, obtain these results.
In speaking with your HCV treatment team of care providers, classify yourself as one of the following response categories: Non-responder, partial responder, responder-relapser, or a null responder. This will help us best treat previously exposed patients who now need re-treatment.

Also See ;
Starting Hepatitis C Treatment: Tips and Information
Two New Videos;
Treating Hepatitis C In 2011 With Boceprevir Or Telaprevir
Melissa Palmer, M.D. on Telaprevir (Vertex Pharmaceuticals) & Boceprevir (Merck), the new protease inhibitor treatments for hepatitis C (HCV).

Before treatment begins you may be given the following tests;

Pre-Testing Boceprevir
Females must have a pregnancy test before starting treatment with VICTRELIS combination therapy, every month while being treated, and every month for 6 months after treatment with VICTRELIS, peginterferon alfa, and ribavirin is over.
*Note; It is also recommended that men and women should not consider pregnancy for 6 months after discontinuation of the drug.

Complete blood count (with white blood cell differential counts) must be conducted in all patients prior to initiating VICTRELIS combination therapy.

Refer to the Package Inserts for Peginterferon alfa and Ribavirin , including pregnancy testing requirements

Pre-testing "standard therapy" 
You will be asked to give a medical history and have a complete medical examination; including but not limited to an eye examination, an EKG (a tracing by machine that shows how well your
heart is working), and/or a cardiac stress test, if the provider thinks they are needed.

A pregnancy test for female patients

Thyroid function should be monitored every 12 weeks while on treatment.

PCR=Viral Load or Quantitative HCV tests measure the number of viral RNA particles in your blood. Viral load tests are often used before and during treatment to help determine response to treatment .

Genotype test; Viral genotyping is used to determine the kind, or genotype, of the virus. There are 6 major types of HCV; the most common in the U.S. and difficult to treat is (genotype 1), genotypes 2 or 3 have a better response rate to HCV treatment. Genotyping is often ordered before treatment is started to give an idea of the likelihood of success and how long treatment may be needed.
 IL28B genotype testing
The assumption is that IL28B testing may be implemented, however at this time the protocol for pre-testing has not been established.

Why Have The Test ?
From HCV Advocate : The gene is a variation of IL28B (interleukin 28B) which triggers our body to make more of a type of natural interferon called lambda interferon. This natural interferon has also been found to help naturally suppress the hepatitis C virus. In people who take interferon plus ribavirin therapy the presence of a certain variation of IL28B gives them a two-fold increased chance of achieving a sustained virological response (HCV RNA negative 24-weeks post treatment) compared to those who do not have this gene variation.

Additional information on IL28B genotype testing can be found here

Laboratory Tests During Treatment
HCV-RNA levels (viral load) should be monitored at Treatment Weeks 4, 8, 12, and 24, at the end of treatment, during treatment follow-up, and for other time points as clinically indicated.

Use of a sensitive real-time reverse-transcription polymerase chain reaction (RT-PCR) assay for monitoring HCV-RNA levels during treatment is recommended. The assay should have a lower limit of HCV-RNA quantification of equal to or less than 25 IU/mL, and a limit of HCV-RNA detection of approximately 10-15 IU/mL.


Treatment Week = (TW)
Standard Therapy = Peginterferon alfa and ribavirin
Response Guided Therapy = (RGT)
Treatment may be response guided which is done by viral load monitoring during treatment. This is intended to enable the physician to determine the duration of combination therapy based on a patients viral response. The quantitative HCV RNA level (viral load test) is used to assess response to therapy and as a guide to discontinue treatment.
A negative viral load test after "four weeks" of therapy is predictive of sustained virologic response. In contrast, failure to achieve a 100-fold reduction in viral load by week 12 of therapy has a strong negative predictive value for sustained virologic response and suggests that treatment is likely ineffective and should be stopped."
The following dosing recommendations differ for some subgroups from the dosing studied in the
Phase 3 trials [see Clinical Studies (14)].
Response-Guided Therapy (RGT) is recommended for most individuals, but longer dosing is recommended in targeted subgroups (e.g., patients with cirrhosis).

See Table 1 below ;  For Guidelines in Patients Without Cirrhosis AND Who Are Previously Untreated or Who Are Previous Partial Responders or Relapsers to Interferon and Ribavirin.
 Prescribing Information
• Initiate therapy with peginterferon alfa and ribavirin for 4 weeks (Treatment Weeks 1-4).
• Add VICTRELIS 800 mg (four 200-mg capsules) orally three times daily (every 7-9 hours) to peginterferon alfa and ribavirin regimen after 4 weeks of treatment.

How Long Will I Be On Treatment ?

Treatment Duration Table 1
Treatment duration will be based on your viral load at Treatment Week 8, Treatment Week 12 and (TW24) (see Table 1) for the "Response-Guided Therapy" (RGT) guidelines to determine duration of treatment

Table 1
Duration of Therapy Using Response-Guided Therapy (RGT) Guidelines in Patients Without Cirrhosis Who Are Previously Untreated or Who Are Previous Partial Responders or Relapsers to Interferon and Ribavirin.

NOTE that null responders are not mentioned, more on this below.

Click On Table 1 To Enlarge

VICTRELIS Combination Therapy: Patients with Cirrhosis
Patients with compensated cirrhosis should receive 4 weeks peginterferon alfa and ribavirin followed by 44 weeks VICTRELIS 800 mg (four 200-mg capsules) three times daily (every 7-9 hours) in combination with peginterferon alfa and ribavirin.

Dose Modification
Dose reduction of VICTRELIS is not recommended.
If a patient has a serious adverse reaction potentially related to peginterferon alfa and/or ribavirin, the peginterferon alfa and/or ribavirin dose should be reduced or discontinued

When To Stop Treatment
If the patient has a (viral load)  greater than or equal to 100 IU/mL at Treatment Week 12, then discontinue three-medicine regimen.

If the patient has confirmed, detectable HCV-RNA (viral load)  at Treatment Week 24, then discontinue three-medicine regimen.

†In clinical trials, HCV-RNA in plasma was measured using a Roche COBAS® TaqMan® assay with a lower limit of quantification of 25 IU/mL and a limit of detection of 9.3 IU/mL.

What If I Miss A Dose
Missed VICTRELIS/boceprevir Doses
If a patient misses a dose and it is less than 2 hours before the next dose is due, the missed dose should be skipped. If a patient misses a dose and it is 2 or more hours before the next dose is due, the patient should take the missed dose with food and resume the normal dosing schedule.Do not double the next dose. If you have questions about what to do, call your healthcare provider.

How Will Boceprevir Be Packaged ?
VICTRELIS is packaged into single daily-use bottles. Each bottle has your entire day’s worth of medicine. Make sure you are taking the correct amount of medicine each time.
Capsules should be refrigerated at 2-8°C (36-46°F) until dispensed. Avoid exposure to excessive heat. For patient use, refrigerated capsules can remain stable until the expiration date printed on the label. VICTRELIS/boceprevir can also be stored at room temperature up to 25°C  (77°F) for 3 months. Keep container tightly closed

One important note here folks is that boceprevir has not been studied in prior null reponders whereas telaprevir has.

Boceprevir HAS not been studied in (prior null responders).

What is a null responder ?

Null responders-
People who failed to reduce their viral load by at least 2 log10 (100 times) after 12 weeks of prior treatment, which is the currently recommended Food and Drug Administration (FDA) definition for clinical trials of investigational hepatitis C treatments.

What Is A 100-fold reduction in viral load ?
Changes in viral load are sometimes expressed in terms of logs: a 1-log change means a 10-fold increase or decrease; a 2-log change is a 100-fold increase or decrease.

What Is A 2 Log Drop?
Example: 2 log drop = 15,000,000 IU/Ml to 150,000 IU/mL; a viral load that starts at 15,000,000 IU/mL and does not decrease to 150,000 IU/mL or lower.

Telaprevir has been studied in (null responders)

Prior Non-responders Achieve Treatment Success with Telaprevir plus Pegylated Interferon and Ribavirin
More than half of genotype 1 chronic hepatitis C patients who were not cured with a previous course of interferon-based therapy achieved sustained virological response (SVR) when treated with the HCV protease inhibitor telaprevir plus pegylated interferon and ribavirin, according to a summary provided by Vertex Pharmaceuticals of a study presented this week at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010) in Vienna. Response varied according to type of previous treatment failure; while almost all prior relapsers achieved SVR, prior null responders had the lowest odds of successful treatment
EASL 2011 Berlin March 31 REALIZE Trial Final Results: Telaprevir-based Regimen for Genotype 1 Hepatitis C Virus Infection in Patients with Prior Null Response, Partial Response or Relapse to Peginterferon/Ribavirin
Also See The Latest Data On Boceprevir and Telaprevir;
Summary of investigational Hepatitis C drugs presented at this months EASL Conference

Side Effects

See VICTRELIS™- Boceprevir: Prescribing Information and Medication Guide  for
complete information.

Adverse events (regardless of investigator's causality assessment) reported in greater than or equal to 10% of subjects receiving the combination of VICTRELIS with PegIntron/REBETOL and reported at a rate of greater than or equal to 5% than PegIntron/REBETOL alone in SPRINT-1, SPRINT-2, and RESPOND-2 trials.

Click On Table 4 To Enlarge
Table 4
Selected Hematological Parameters

Common side effects;
Fatigue, headache, and nausea. Anemia  occurred about twice as often treating with boceprevir
then with standard therapy. Adverse events such as dry mouth, nausea,vomiting and diarrhea were also reported at an increased frequency in subjects receiving VICTRELIS in combination with peginterferon alfa and ribavirin.

Blood problems.
VICTRELIS can affect your bone marrow and cause low red blood cell, and low white blood cell, counts. In some people, these blood counts may fall to dangerously low levels. If your blood cell counts become very low, you can get anemia or infections.
HCV Treatment and Neutropenia(low white count)

How To Figure Out Your Neutrophil Count 
Neutrophil% x White Blood Cell = Absolute Neutrophil Count
For example, if a person's white blood cell count were 6,000 cells, and neutrophils made up 50% of those, that person's absolute neutrophil count would be 3,000.
A normal range for neutrophil% is between 33% and 72%. This makes the normal range for the ANC between 1500 and 7200. Since every individual is unique, you should consult your physician or nurse if you have questions concerning your white blood cell count and ANC.
If you’re total white count is 1.0 (1000) or below then your neutrophils would be around 500… to low to continue therapy. Although treatment is not always discontinued (in some cases) the dose is cut back until the white count increases.

Neutropenia (Use with Ribavirin and Peginterferon Alfa)
In Phase 2 and 3 clinical trials, seven percent of subjects receiving the combination of VICTRELIS with PegIntron/REBETOL had neutrophil counts of less than 0.5 x 109/L compared to 4% of subjects receiving
PegIntron/REBETOL alone. Three subjects experienced severe or life-threatening infections associated with neutropenia, and two subjects experienced life-threatening neutropenia while receiving the combination of VICTRELIS with PegIntron/REBETOL. Complete blood count (with white blood cell differential counts) must be conducted in all patients prior to initiating VICTRELIS combination therapy. Complete blood counts should be obtained at Treatment Weeks 4, 8, and 12, and should be monitored closely at other time points, as clinically appropriate. Decreases in neutrophil counts may require dose reduction or discontinuation of peginterferon alfa and ribavirin.
Refer to Package Inserts for peginterferon alfa and ribavirin for additional information regarding dose reduction or discontinuation for peginterferon alfa and ribavirin.

Anemia (Use with Ribavirin and Peginterferon Alfa)
Anemia has been reported with peginterferon alfa and ribavirin therapy. The addition of VICTRELIS to peginterferon alfa and ribavirin is associated with an additional decrease in hemoglobin concentrations.

Complete blood counts should be obtained pretreatment, and at Treatment Weeks 4, 8, and 12, and should be monitored closely at other time points, as clinically appropriate. If hemoglobin is less than 10 g/dL, a decrease in dosage or interruption of ribavirin is recommended; and if hemoglobin is less than 8.5 g/dL, discontinuation of ribavirin is recommended [see Adverse Reactions (6.1) and Clinical Studies (14)].r
efer to the Package Insert for ribavirin for additional information regarding dosage reduction and/or interruption.

Also See; Hepatitis C: Anemia And Other Side Effects During Treatment
Neutrophils and Platelets
The proportion of subjects with decreased neutrophil and platelet counts was higher in the VICTRELIS-containing arms compared to subjects receiving PegIntron/REBETOL alone. Three percent of subjects receiving the combination of VICTRELIS with PegIntron/REBETOL had platelet counts of less than 50 x 109/L compared to 1% of subjects receiving PegIntron/REBETOL alone. Decreases in neutrophils or platelets may require a decrease in dosage or interruption of peginterferon alfa, or discontinuation of therapy [see Package Inserts for peginterferon alfa and ribavirin].

See All Side Effect Data When Treating With Peginterferon and Ribavirin Available On The Blog

For additional information on side effects  which has not been covered in this entry please see VICTRELIS™- Boceprevir: Prescribing Information and Medication Guide

Also See Telapreivr and Boceprevir Side Effects 
Side Effects:  Peginterferon and Ribavirin

What are the stats on successfully achieving SVR= a cure ?
Breaking Down Both Studies;

In the first trial, the SPRINT-2 Investigators enrolled 938 non-black and 159 black adult patients with previously untreated HCV genotype 1 infection (blacks and non-black cohorts were enrolled and analyzed separately as blacks are known to have a much lower response rate to standard therapy). After undergoing a 4-week lead-in with peginterferon alfa-2b plus ribavirin, patients were randomized to one of the following groups:

1) Peginterferon/ribavirin/placebo for 44 weeks (“standard therapy”)

2) Peginterferon/ribavirin/boceprevir for 24 weeks, with an additional 20 weeks of peginterferon/ribavirin/placebo if HCV RNA was detected between weeks 8 and 24 (“response-guided therapy”)

3) Peginterferon/ribavirin/boceprevir for 44 weeks (“48-week therapy”)

SVR rates 24 weeks after completion of treatment were significantly higher in the boceprevir arms than in the standard therapy control group.

In an intent-to-treat analysis, 68% of non-black patients receiving fixed-duration triple therapy and 67% receiving response-guided therapy achieved SVR, compared with 40% in the control group.

Among black patients the corresponding SVR rates were 53%, 42%, and 23%, respectively.

Relapse rates in both fixed duration and response-guided boceprevir arms were significantly lower than in the standard-therapy control group.

Almost all boceprevir recipients with undetectable HCV RNA during weeks 8 through 24 went on to achieve SVR.


In the second trial, the HCV RESPOND-2 enrolled 403 subjects with HCV genotype 1 infection that had not responded to or had relapsed after prior treatment with standard peginterferon/ribavirin therapy.

Subjects were randomized to three arms very similar to those described for SPRINT-2:

Standard therapy, response-guided therapy (here after 32-weeks of triple therapy), or 48-week therapy. On the primary endpoint, subjects receiving boceprevir (i.e. those in the response-guided and 48-week therapy arms) again had significantly higher rates of SVR measured at 24 weeks after completion of therapy .

All participants initially received pegylated interferon/ribavirin for a 4-week lead-in period. They were randomly assigned to subsequently continue on pegylated interferon/ribavirin plus placebo for 44 more weeks or to add 800 mg 3-times-daily boceprevir.

Boceprevir recipients either stayed on triple therapy for 44 more weeks or used response-guided therapy. The latter group stopped boceprevir at week 36; those who had detectable HCV RNA at week 8 continued on pegylated interferon/ribavirin through week 48.


In an intent-to-treat analysis, patients in the boceprevir arms again had significantly higher SVR rates -- 66% with fixed-duration therapy and 59% with response-guided therapy -- than those in the standard therapy control group (21%).

Among people with undetectable HCV RNA at week 8, SVR rates were 86% after 32 weeks and 88% after 44 weeks of triple therapy.

Among participants who had less than a 1 log IU/mL decrease in HCV RNA at week 4, one-third of boceprevir recipients still achieved SVR, compared with none in the control group.

"The addition of boceprevir to peginterferon/ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with peginterferon/ribavirin alone," the investigators concluded, noting that fixed-duration and response-guided therapy were similarly effective.

Patients who previously relapsed after receiving standard therapy had SVR rates of up to 75% on boceprevir triple therapy, while previous non-responders had sustained response rates of 40% to 52%, they added in their discussion.

In summary, they wrote, the results of this trial "show that boceprevir, when added to peginterferon alfa-2b and ribavirin, leads to high rates of sustained virologic response in difficult-to-treat patients."


For additional information which has not been covered in this entry please see VICTRELIS™- Boceprevir: Prescribing Information and Medication Guide . Merck has suggested that  because the information may change you should read the Medication Guide before you start taking VICTRELIS, and each time you get a refill.

Questions To Ask Your Healthcare Provider About Medical Treatment

– What will happen if I decide to wait to start treatment?
 What are the pros and cons of beginning treatment?
– What are the potential side effects of the interferon and ribavirin,
pegylated interferon or when adding the new oral inhibitors ?
How long do you think I will have to be on therapy?
– How is the treatment taken?
– How may the treatment affect my life and my lifestyle?
– What is the likelihood that the treatment will be successful?
 If I have a history of mental health issues (depression/anxiety), will I
be a candidate for hepatitis C treatment?
– How will my mental health be managed?
– What will be done if my mental health gets worse?

Also See :
Preparing You and Your Family Before You Start Treatment
Treating Hepatitis C; Improving Your Shot At A Cure
Treating Hepatitis C In 2011; The Bible Of Links

I want to offer my heartfelt sincere sentiments to all those people living with HCV and I wish each person fortunate enough to embark on therapy a safe, and successful journey.

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