Costs Associated with Protease Inhibitor-Based Combination/Rescue Drugs/AASLD 2010

Michigan painter Robert Thom, originally painted for Parke-Davis 1930-1940

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With compelling interest I have been browsing the available abstracts that will be presented at the AASLD. These abstracts are available to the public at the AASLD website. On this blog there are a few abstracts of interest which can be found here.
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This morning while looking for abstracts on protease inhibitors I found a few in particular that I wanted to share with you. One abstract covers the cost of the rescue drugs that may be needed during these trials and is compared in cost to standard therapy, very interesting. The other abstract is pertaining to the adverse effects treating with triple therapy.

*new PIs and standard of care = Triple Therapy
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The HCV community has been waiting for the results of these new PIs and the hope is these drugs will be the magic bullet for treating HCV. There is a large population of individuals where standard therapy hasn't worked, and these new drugs may be their chance for a cure. There is also a new population of HCV infected people who have acquired this disease more recently in a clinical setting or with IV drug use. An additional portion of people infected with HCV have just been diagnosed after years of being infected because in the world of healthcare falling through the cracks can be a sad reality. These groups may be forgoing HCV treatment with SOC hoping to treat with Telaprevir, Boceprevir or with other drugs coming down the pipeline.
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The outcome of this meeting (AASLD) will bring the anticipated data needed to proceed with your particular treatment decision. So far the outcomes shown in clinical trials with these new drugs have been impressive.
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Understanding that trials have inclusion and exclusion data
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In the world of clinical trials sometimes people assume these trials only include hand picked subjects in order to show the best results. It can be difficult to collect substantial data when only testing a few variables, but they cannot open these trials to everyone in each trial.
Trials have inclusion and exclusion data for the purpose of producing results that are used after FDA approval by physicians treating their patients.
However in the clinical trials for Telaprevir and Boceprevir they have included the difficult to treat population.
In Telaprevir they included people that never treated before but also included people that failed in SOC therapy.
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Telaprevir:
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"Telaprevir, the company’s experimental drug, helped 65 percent of hepatitis C patients whose prior therapies were unsuccessful. This was the last of 3 major phases of telaprevir conducted by Vertex and partner Johnson & Johnson, previous ones released in May and August this year.“This last phase III study, dubbed "Realize," was set up to confirm previous, earlier findings that showed telaprevir could cure a significant number of hepatitis C patients without treatment options because they failed to respond to the current standard of care”, the officials revealed. Details of the trial looked at 662 hepatitis C patients whose bodies seemed to be resistant to all other treatments."

http://www.themedguru.com/20100908/newsfeature/new-drug-vertex-can-treat-hard-cure-hepatitis-c-patients-86140245.html
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Boceprevir:
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"The AASLD presentations of the boceprevir Phase III data will include sustained virologic response (SVR)1 rates by patient sub-groups, including treatment-naïve patients (African-American/Black and non-African-American/Black), patients who experienced prior relapse, prior non-responders, and patients with a poor response to interferon, defined as having achieved less than a 1 log decrease in viral load (HCV-RNA) after a 4-week Peg/riba lead-in period. "
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Evaluating The Data
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I can't stress enough the importance of being informed and to evaluate all the data ( if available) before entering into a clinical trial or making any treatment decisions. Unfortunately when you are in the fight for your life this step isn't addressed and is far too often forgotten. Years ago when I entered my own clinical trial I signed on the dotted line with my eyes closed and my hopes high. I was successful in my effort and achieved my cure. But, I was not successful in acquiring the knowledge needed before I entered the trial. I treated for almost a year with a 2 genotype, on a high dose of Intron A in combination with ribavirin, I was a fool, if I would have waited for a year my treatment regimen would have been for six months, with a much lower dose of interferon. In my rush to find a cure I didn't wait for PegIntron or Pegasys to be FDA approved, I made a huge mistake. Unfortunately I didn't know enough to wait, and look into the pegylated trials, I didn't know what I was doing, but I hope you will.
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Ask Questions
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Ask questions about the "rescue" drugs and if they will be allowed and paid for during the trial.
You need to know the trial regulations , talk to your doctor or trial coordinator about their policy around dosage reductions to manage adverse effects. Only by educating ourselves can we enter into a trial with a peace of mind and the confidence required to stay the course of therapy. .

The Perks

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Entering into a clinical trial gives you the ability of being involved in your own treatment decisions. One of the benefits of being in a trial is gaining access to potentially new drugs and receiving expert care by HCV specialists who are on the cutting edge of the research. Most costs are covered which allows people without insurance a chance for treatment. ,

One way to start is to understand the phases of these trials.
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Understanding The Phases
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First the drugs are tested in animals and if they are found to be safe the next step is applying to the FDA for permission to continue.

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Phase 1

The first phase is to find out the safety and effectiveness using short or limited dosing.
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Phase 2
This phase is a little more intense but still will answer those same questions by using a larger group of people with longer dosing. Remembering that in this phase of the trial, the best dosage profile is still being worked out, therefore can be riskier then in a Phase 3 trial. The goal is to find out the actual treatment dosage and treatment duration.
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Phase 3
This phase is generally the final phase, and the dose, treatment durations, and target cure (SVR) rates are all worked out for what will be the finished product and treatment protocol after FDA approval.
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After the end of a Phase 3 trial the company files a (new drug application) NDA and the FDA reviews all the data from the trials and then the FDA will either approve, reject, or ask for additional testing.
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Rarely is there a Phase 4
After the drug is approved and marketed, the FDA may require a
company to obtain more information about the drug and additional tests are required.
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Additional Information
Making Sense of Hepatitis C Research and Medical Literature
How to Evaluate a Clinical Trial
Guide to Understanding Clinical Trials and Medical Research in Hepatitis C
Forum To Ask Questions About The New PI Trials
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The Cost Of Rescue Drugs/The Adstract
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The costs to manage Adverse Events or AEs (side effects)
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Estimation
Up to $4825 for anemia (assuming epo use rate of 22%),
$2837 for depression
$566 for diarrhea
$633 for rash.
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PITT= Protease Inhibitors for Triple Therapy
AE = Adverse Events
SOC = Standard Of Care

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Adverse Event-Related Treatment Costs Associated with Protease Inhibitor-Based Combination Therapy for Hepatitis

C J. M. Stephens1; J. Carter1; X. Gao1; S. Haider2; V. K. Rustgi3 1. Pharmerit North America LLC, Bethesda, MD, United States. 2. Pfizer Inc, New London, CT, United States. 3. Georgetown University Medical Center, Washington, DC, United States.

It is anticipated that the current standard of care (SOC: PEGIFN/RBV for 48 weeks) for the treatment of hepatitis C (HCV) will shift to a triple therapy approach. The first class of agents to be added to SOC is the protease inhibitors for triple therapy (PITT). Although the viral load reduction associated with protease inhibitors (PIs) is well documented, no study of the impact on costs related to PITT has been performed; particularly, those associated to adverse events (AEs). Our objective was to describe the incremental AE costs of PITT over SOC.

METHODS:
A comprehensive literature search of the past 5 years was conducted to identify clinical trial studies for PITT and SOC. We developed an economic analysis of the incremental costs of treating AEs in PITT (24-48 weeks) vs. SOC (48 weeks) based on AE incidence rates in PITT and SOC arms within PITT clinical trials. Medical interventions for AEs were drawn from SOC and PITT trials. Medication prices to treat AEs were based on 2009 US dollars (AWP-Redbook), and medical fees were based on standard 50th percentile costs for CPT codes from the 2009 National Fee Analyzer (Ingenix).

RESULTS:
A total of 5 SOC and 7 PITT trials were identified. Of the PITT trials, 3 (2 telaprevir; 1 boceprevir) contained a 48-wk SOC comparison arm. Average costs to manage an AE episode were estimated at up to $4825 for anemia (assuming epo use rate of 22%), $2837 for depression, $566 for diarrhea, and $633 for rash. The relative weighted AE incidence (w/ weighted avg total AE cost per patient) for SOC, telaprevir-based, and boceprevir-based PITT respectively are shown in the table . The incremental cost to treat PITT-related AEs averaged >30% higher than SOC (range 8-60%).

CONCLUSIONS:
PITT may be associated with greater costs to manage AEs compared with SOC. Future studies should incorporate the economic burden of the AE profile, the total cost and value of treatment based on long term outcomes, and the effect of treatment-related AEs on the ability to achieve sustained viral response.

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New PIs : The Challenges
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Novel Protease Inhibitors for Chronic Hepatitis C Treatment: Issues and Challenges Associated with Health-Related Quality of Life
(HRQoL) X. Gao1; J. Carter1; J. M. Stephens1; S. Haider2; V. K. Rustgi3 1. Pharmerit North America LLC, Bethesda, MD, United States. 2. Pfizer Inc, New London, CT, United States. 3. Georgetown University Medical Center, Washington, DC, United States.

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.Although the efficacy of the addition of protease inhibitors (PIs) in combination with standard of care (SOC – PEGIFN/RBV for 24 or 48 weeks) on viral load reduction in hepatitis C is well documented, no study on the impact of PI triple therapy (PITT = PI + SOC) on patients’ HRQoL has been conducted. Our objectives were to describe the potential HRQoL impact of PITT based on treatment safety/tolerability, efficacy and treatment adherence profiles, and to identify challenges in assessing HRQoL impact.
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METHODS:
A comprehensive literature search was conducted to identify clinical trial studies/abstracts for PITT (2007-present) and SOC incorporating HCV-validated HRQoL measures (2000-present). PITT was compared with SOC on early/sustained viral response and treatment duration. HRQoL and safety data were synthesized by study design, sample characteristics, HRQoL instrument, treatment discontinuation, and adverse events (AEs).
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RESULTS:
Literature review yielded 7 PITT and 23 SOC trials matching our search criteria. Commonly reported AEs in PITT trials were GI symptoms (i.e., nausea) (20-90%), fatigue (30-74%), headache (15-88%), insomnia (17-31%), and rash (43-55%). The table shows absolute AE rate differentials when SOC is compared to PITT. Nearly 20% of patients discontinued PITT by week 22. The SOC trials revealed 11 HRQoL instruments (6 are hepatitis C-validated). The 36-item Short Form (SF-36), the Hepatitis Quality of Life Questionnaire (HQLQ), and the Fatigue Severity Scale (FSS) were the most commonly used hepatitis C-validated instruments. Significant domain changes from baseline (p =0.05-0.0001) were most often seen in vitality, depression, physical limitations, and fatigue during treatment or follow-up periods.
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CONCLUSIONS:
The findings show similarities between types of AEs reported, although a trend was noted of increased incidence for PITT. Similar impact on specific domains of HRQoL instruments were commonly reported. While 4 of the commonly reported AEs could be linked to 3 specific HRQoL domains, fatigue and insomnia to fatigue and vitality domains and headache and rash linked to the physical limitations domain, there may be gaps in assessment of symptom burden with existing instruments. Future research on PIs in HCV should include appropriate use of patient-reported outcome tools to capture potential HRQoL differences among treatment strategies. Differences in absolute rates of AEs for PITT vs SOC
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24-Week PITT vs. SOC.............. 48-Week PITT vs. SOC
Rash........................+35%.........................+ 29%
Nausea...................+12%.........................+17%
Fatigue.. ...............+5% ..........................+9%
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You can find information about clinical trials currently being conducted by searching http://www.clinicaltrials.gov/

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