Another Costly Drug Approval Keeps Spotlight on Hepatitis C

Boston—Hepatitis C virus (HCV) has been a top concern for many healthcare providers, payers, and patients for the past year since the approvals of the costly medications simeprevir, a protease inhibitor, in November 2013, and sofosbuvir, a polymerase inhibitor, in December 2013. Once again, HCV is at the forefront of discussions as the FDA just recently approved the first once-daily oral combination of ledipasvir and sofosbuvir to treat HCV genotype 1 infection, which comes with an even larger pricetag: $94,500 for a 12-week course of treatment.

Just hours before the FDA approved ledipasvir/sofosbuvir, experts discussed trends and projections for HCV in a satellite symposium at the AMCP meeting. The session was supported by an educational grant from Gilead Sciences, Inc.
Hepatitis C is a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure. Most people infected with HCV have no symptoms of the disease until liver damage becomes apparent, which may take decades, according to an FDA news release.

Jeffrey D. Dunn, PharmD, MBA, senior vice president, VRx Pharmacy Services, LLC, editorial advisory board member, First Report Managed Care, opened the session by detailing the growing prevalence and clinical burden of HCV. Approximately 1.6% of the US population, or 4.1 million individuals, have HCV, according to the Centers for Disease Control and Prevention.

The prevalence is expected to increase over the next 3 decades, as the majority of currently infected individuals are unaware that they have the disease. HCV is the leading cause of liver disease, with 40% of deaths from liver disease attributed to HCV. In addition, HCV-related cirrhosis accounts for approximately 40% of liver transplants [Ann Transplant. 2012;17(4):5-10].

Patient engagement in HCV care is lacking, said Dr. Dunn, noting a study that found the following [N Engl J Med. 2013;368(20):1859-1861]:
• 3.2 million people have chronic HCV infection
• 1.6 million people with HCV (50%) have been tested for the disease
• 1 million to 1.2 million people with HCV (32%-38%) have been referred to care
• 630,000 to 750,000 people with HCV (20%-23%) have received HCV ribonucleic acid testing
• 380,000 to 560,000 people with HCV (12%-18%) have received a liver biopsy
• 220,000 to 360,000 people with HCV (7%-11%) have been treated for the disease
• 170,000 to 200,000 people with HCV (5%-6%) have achieved sustained virologic response (SVR)

While many patients with HCV are not receiving proper care, the economic burden of HCV continues to increase. In 2011, $6.5 billion total healthcare costs were attributed to HCV, and by 2024, it is projected that the costs will reach $9.1 billion. Dr. Dunn said this increase is due to the new, costly medications. Increased costs are also attributed to more advanced liver diseases, including decompensated cirrhosis (46%), compensated cirrhosis (20%), and hepatocellular carcinoma (16%).

Dr. Dunn noted the following challenges presented to managed care by HCV:
• Improved methods to enhance identification and treatment of affected patients are needed
• Patient adherence to therapy is suboptimal
• Long-term monitoring of patients is necessary to enhance treatment outcomes
• The disease is associated with significant and costly comorbidities, including HIV
• Current therapies have limitations, including adverse events and convenience issues

With another recent drug approval and still more in the pipeline, Dr. Dunn said, “This will get interesting over the next few years.  It is going to get much more complicated.”

Right Treatment, Right Patient, Right Time
Nancy S. Reau, MD, associate professor of medicine, The University of Chicago Medicine, who was involved in compiling the recent American Association for the Study of Liver Diseases hepatitis C practice guidelines, continued the session by discussing patient requirements for HCV therapy, noting that patients with the most immediate need should be prioritized to receive therapy. These patient characteristics include those who are high-risk for liver-related complications, high-risk for progression, high-risk for transmission, and those with serious extrahepatic complications, which include hematologic disorders, renal impairment, dermatologic diseases, diabetes mellitus, autoimmune disorders, ophthalmologic features, and neurologic issues.

In addition, a recent study projecting cancer incidence and mortalities in the United States found that while lung cancer is projected to remain the number 1 cancer-related mortality, pancreatic and liver cancers are projected to surpass breast, prostate, and colorectal cancers to secure the second and third slots, respectively, of leading causes of cancer-related deaths by 2030 [Cancer Res. 2014;74(11):2913-2921]. “Increased liver cancer [will lead] to a host of other problems,” said Dr. Reau.

She also discussed current and projected HCV regimens, noting multiple times throughout the presentation that this is “going to change today,” as she discussed treatment options just hours before ledipasvir/sofosbuvir was FDA-approved. With the recent approvals of simeprevir and sofosbuvir, SVR rates have exceeded 90%. “If you cannot guarantee a 95% cure rate, your drug will not make it in the market today,” said Dr. Reau.
Though there has been debate over the hefty pricetag accompanying the newer HCV drug approvals, Dr. Reau said, “[Patients] who would have been almost impossible to cure with previous therapies,” are now finding success with new regimens. She noted that, “Special populations are no longer special.” The ledipasvir/sofosbuvir oral therapy approved just weeks ago is also expected to be followed by an all-oral regimen from AbbVie in December.

Dr. Reau highlighted the short- and long-term outcomes of improved SVR, including improved histology; decreased risk of cirrhosis, liver cancer, and transplantation; improved quality of life; improved insulin resistance; and decreased all-cause mortality.

Pharmacy Benefit Management for HCV
HCV has quickly become a top 10 specialty pharmacy category under the pharmacy benefit. “Four years ago, hepatitis C was not on this list,” said Dr. Dunn (Table). As discussed by both speakers, patient nonadherence to HCV drug regimens remains a top concern and is a leading driver of increased economic burden for this disease state. Dr. Dunn said a balance between shifting costs and patient nonadherence is challenging. Member decision factors include cost-sharing, compliance, and efficacy and tolerability, while benefit design factors include medical versus pharmacy benefits, copayment versus coinsurance options, and specialty tiers.

Common components of benefit design include cost management and utilization management. For cost management, drug discounts, channel management, rebates, and benefit design options are considered. For utilization management, medical necessity review, clinical management via treatment algorithms, prior authorization, and formulary management are considered.

“Behavioral changes are needed in this disease state for optimal outcomes,” said Dr. Dunn. “Patients need to buy in to treatment regimens.” He said all healthcare stakeholders need to work together to improve patient adherence and reduce the overall economic burden. He mentioned that partnerships between specialty pharmacies and health plans can improve patient outcomes while lowering overall costs. Greater collaboration between providers and adherence programs can improve clinical outcomes, while a single point of patient contact and connections to related services may help to improve the patient’s care experience. By synchronizing medical and pharmacy services, total cost savings can be significant, according to Dr. Dunn.

He encouraged the collaboration between specialty pharmacists, physicians, and nurses to improve adherence by:
• Verifying diagnosis and presence of comorbidities
• Ensuring treatment is aligned with guidelines
• Monitoring and adjusting therapy to optimize clinical response
• Minimizing treatment duplication and over- or underdosing
• Managing issues related to the complexity of treatment
• Identifying and addressing barriers to adherence
• Identifying gaps in patient care
• Providing patient and caregiver education

In conclusion, Dr. Dunn noted that HCV has become 1 of the most important categories to manage. “Hepatitis C is a top 5 specialty trend [that] was not on our radar just a few years ago,” he said.
 
The Newest HCV Drug Approval
With the third drug approval for HCV in the past year, this disease state remains a frontrunner for cost concerns. The ledipasvir/sofosbuvir regimen is the first treatment that does not require administration with interferon or ribavirin, 2 FDA-approved drugs also used to treat HCV infection. Both ledipasvir and sofosbuvir interfere with the enzymes needed for HCV to multiply.

The efficacy of ledipasvir/sofosbuvir was evaluated in 3 clinical trials that included 1518 participants who were treatment-naïve or treatment-experienced, including participants with cirrhosis. Participants were randomly assigned to receive ledipasvir/sofosbuvir with or without ribavirin. The trials were designed to measure whether HCV was no longer detected in the blood at least 12 weeks after finishing treatment, indicating that a participant’s HCV infection had been cured.
In the first trial that included treatment-naïve participants, 94% of those who received ledipasvir/sofosbuvir for 8 weeks and 96% of those who received ledipasvir/sofosbuvir for 12 weeks achieved SVR. The second trial found 99% of participants with and without cirrhosis achieved SVR after 12 weeks. In the third trial, which examined the efficacy of ledipasvir/sofosbuvir in treatment-experienced participants with and without cirrhosis, 94% of those who received ledipasvir/sofosbuvir for 12 weeks and 99% of those who received ledipasvir/sofosbuvir for 24 weeks achieved SVR. In all trials, ribavirin did not increase response rates.

The most commonly reported side effects of ledipasvir/sofosbuvir included fatigue and headache.

Gilead Sciences, Inc., the drug’s manufacturer, said the combination includes the NS5A inhibitor ledipasvir 90 mg and the nucleotide analog polymerase inhibitor sofosbuvir 400 mg.—Kerri Fitzgerald