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Interferon-free solutions expected soon.
The standard of care for Hepatitis C (HCV) was uprooted in 2011. Prevailing treatment involved a combination of two drugs-pegylated-interferon and anti-viral ribavirin-taken for one year. Two new protease inhibitors, boceprevir and telaprevir, joined the regimen.
While the multidrug combination reduces treatment timelines to 24 to 48 weeks, its complexity also hampers adherence.
Patients only take telaprevir for the first 12 weeks of treatment on a specific dosing schedule. An additional 12 or 36 weeks of peginterferon alfa and ribavirin is also required.
A clinical study from Weill Cornell Medical College known as ADVANCE, comparing patients on standard two-drug therapy to those on a 12-week course with the triple combination therapy of protease inhibitors followed by standard care, found a sustained response of 44% versus 79%, respectively. In other words, telaprevir with peginterferon-ribavirin, as compared with peginterferon-ribavirin alone, was associated with better outcomes.
HCV patients typically have adherence issues with the prevailing therapy because of side effects, and the added complexity of self-management of multiple drugs exacerbates the problem. Patient lack of adherence with interferon is often attributed to depression, pain, fatigue, chronic pain and flu-like side effects.
The inherent complexity of managing hepatitis C patients has rallied specialty pharmacies, many of which have developed care management programs targeting HCV.
Andrew Muir, MD, director of gastroenterology and hepatology research at Duke University School of Medicine, says one of the biggest challenges for HCV is the large number of people who do not know they are infected. And once the condition is detected, most don’t know how long they have had it.
“Since liver damage is not always related to how long someone has had HCV,” he says, “there is an opportunity to develop a liver wellness strategy, not just related to drugs but also to care coordination and affordability.”
Paul Turner, MD, therapeutic strategy lead for Quintiles, a biopharmaceutical services company based in Durham, N.C., anticipates that the advent of new therapies and recommended testing by the Centers for Disease Control and Prevention (CDC) will raise awareness. Although HCV does not have strong awareness campaigns like HIV does, more Americans now die of HCV than HIV.
Last year, the CDC recommended that everyone born during the years 1945 through 1965 receive a one-time blood test for HCV to potentially uncover an estimated 800,000 undiagnosed cases of the disease. The CDC says that baby boomers are five times more likely than other adults to be infected.
Approximately 3.2 million Americans have chronic HCV virus infection, with an estimated 40,000 new infections per year, according to the World Health Organization. By 2029, total annual medical costs in the United States for people with the condition are expected to more than double, from $30 billion in 2009 to approximately $85 billion.
Express Scripts, a pharmacy benefits manager (PBM) headquartered in St. Louis, has adopted adherence initiatives HCV. Mary Dorholt, vice president, clinical practice lead for specialty pharmacy, says the programs fit into a consumer-based, behavioral sciences approach to healthcare.
Patients might be prescribed telaprevir three times a day, seven to nine hours apart, always taken with food. A meal or snack containing about 20 grams of fat within 30 minutes before each dose is recommended. Treatment would include ribavirin twice a day and a weekly injection of interferon.
“We are helping patients to better understand how to manage side effects from therapy, such as scheduling doses so they won’t interfere with a work schedule; partnering patients with someone who can support their therapy; anticipating when patients need drug refills; and solving member cost issues,” Dorholt says.
Express Scripts’ care management program targeting HCV provides specialty pharmacist support to patients, including a log to schedule blood tests that help regulate drug dosage and length of therapy. The results dictate how the PBM can facilitate ongoing treatment education and follow-up.
Patients also receive a treatment diary to document when they take medications, dosages, side effects and the medications they are taking to manage side effects.
In addition, a new video-based virtual coaching tool provides patients with information on how a protease inhibitor works to prevent the virus from reproducing, along with instructions on how to schedule doses, what types of food to take with medications and the time required in between doses.
The Express Scripts Drug Trend Report 2012 indicates that total drug trend for the HCV therapy at the end of 2011 was 194.8%, more than 10 times the total trend for any other specialty therapy class, with the average cost per prescription rising to $3,370.99 (up from $1,389.04 in 2010). The increase in utilization for drugs slowed during 2012, resulting in a total trend of 33.7%.
“The triple therapy and its significant side effects make self-management difficult,” says Sumit Dutta, MD, senior vice president and chief medical officer of Catamaran, a PBM based in Lisle, Ill.
Dr. Dutta says that specialty pharmacy is an ideal model for not only managing the disease itself, but also associated conditions such as depression.
Catamaran pharmacists contact patients prior to shipment of medication to offer counseling. Educational materials on side effects are included in shipments. Patients also receive calls from nurses at least two times during the first month of therapy to discuss side effects and barriers to adherence and continue during the next three months as needed.
The PBM’s systems document laboratory information, such as viral load levels and hemoglobin, to gauge treatment response and anemia.
Over a six-month period, a comparison of two groups-program enrollees and those not enrolled-showed a 5% increase in the medication possession rate using the model.
Walgreens Specialty Pharmacy maintained medication adherence rates of 93% to 95% when moving patients from double therapy to the more complicated triple therapy regimen, says Rick Miller, director, clinical services for the pharmacy.
“Our ConnectedCare high-touch, clinical program for diseases requiring specialty pharmaceuticals, such as hepatitis C, focuses on ensuring that patients understand how and when to take their medications, assesses barriers to adherence, manages issues related to side effects and educates patients about therapy expectations,” he says.
Walgreens also collects and reviews lab data to determine if a patient’s response to therapy could lead to recommendations for discontinuing medications, Miller says.
Walgreens’ program utilizes care management services via a call center but has supplemented triage by identifying 77 health system and retail locations closely associated with physicians to provide face-to-face intervention.
Walgreens Specialty Pharmacy sponsors national HCV screening days at its retail stores targeting those markets with a larger baby boomer population.
The industry is moving quickly toward transforming therapy once again by bringing interferon-free options to market for patients with genotypes 1, 2 and 3 hepatitis C. The therapy for type 1 is expected by 2015, the latter two for 2014. According to GBI Research, the market for interferon-free treatments could increase to $15 billion by 2015.
Gilead Sciences is one of the organizations developing an option to treat patients with genotypes 2 and 3 HCV. In early April, the company applied for FDA approval for its oral pill sofosbuvir taken in combination with ribavirin. Gilead said a late-stage trial testing of the drug showed no detectable virus level in 73% of study patients after 16 weeks of therapy.
Santaris Pharma A/S, a clinical-stage biopharmaceutical company, conducted a phase 2a trial for miravirsen, the first microRNA-targeted drug for genotype 1 to enter clinical trials. The results, reported in the online edition of the New England Journal of Medicine on March 27, 2013, indicate that four out of nine patients treated at the highest dose of miravirsen (7 mg per kilogram of weight) became HCV RNA-undetectable with just five weekly doses and without any discontinuation related to adverse effects.
Paul Turner, MD, therapeutic strategy lead for Quintiles, a biopharmaceutical services company, attributes the current decrease in utilization of HCV medications to a trend in warehousing patients until new interferon-free therapies are available. They are expected to cause fewer side effects and can be taken for a shorter duration and fewer times a day.
Because HCV may take years to show any evidence of liver damage, Dr. Turner says it might be safe for some patients to wait until the arrival of interferon-free solutions.
“It depends on clinical factors for each patient in terms of warehousing. If a simpler solution or more potent therapy becomes available in the near future, it may be beneficial to ‘wait and see,’” says Glen Pietrandoni, senior manager for HIV/AIDS and HCV pharmacy services, Walgreens Specialty Pharmacy.