Hepatitis C Treatment Options Likely to Expand

San Diego—The FDA approvals of boceprevir and telaprevir in 2011 were seen as breakthroughs in treating patients with hepatitis C. The oral drugs are protease inhibitors used in combination with pegylated interferon and ribavirin. These therapeutic regimens are expensive, require several pills per day, and are only intended for genotype 1 disease.

Several pharmaceutical companies are now developing drugs that could lead to improvements in caring for hepatitis C patients. At the AMCP meeting, a trio of healthcare professionals discussed the history of the disease and the need for medicines that treat all genotypes, require less frequent dosing, and have a shorter treatment duration. They spoke at a Satellite Symposium titled Expanding Horizons for the Management of Hepatitis C: A 2013 Update for Pharmacists.

Ahmet Gurakar, MD, medical director of liver transplantation at Johns Hopkins University School of Medicine in Baltimore, Maryland, said an estimated 140 million to 170 million people worldwide are infected with hepatitis C, including 3.9 million in the United States. Each year in the United States, there are approximately 12,000 hepatitis C-related deaths.

Although 80% to 90% of patients with hepatitis C develop chronic liver disease, the FDA-approved drugs are not effective once patients undergo liver transplantation, according to Dr. Gurakar.

Treatments for hepatitis C began in 1989 with interferon taken 3 times per week and expanded to pegylated interferon plus ribavirin in 2002. Dr. Gurakar said physicians believed then that the combination of pegylated interferon and ribavirin could cure the disease; however, it is only effective for half of patients with hepatitis C and is currently used for genotype 2 and 3. They were similarly confident about boceprevir and telaprevir, although those drugs are limited to a single genotype.

Other limitations of the hepatitis C treatments include side effects such as rash, heavy pill burdens, and protease inhibitor-resistant strains that can emerge 24 to 48 hours after ingestion. Dr. Gurakar said patients sometimes do not adhere to triple drug therapies because they have adverse side effects and experience drug-drug interactions.

“We are realizing we need better medicines to prevent progression in this disease,” Dr. Gurakar said.

Jeremy Shafer, PharmD, MBA, senior director of specialty solutions at Prime Therapeutics LLC, said the newer drugs are expensive, too. In May 2011, before boceprevir and telaprevir were approved, Prime Therapeutics data predicted the drugs would cost $13.10 and $97.62 per pill, respectively. However, as of September 2012, the prices had increased to $14.99 and $109.67 per pill, respectively. Patients take either four, 800-mg tablets of boceprevir 3 times daily with food, or two, 750-mg telaprevir pills 3 times per day with food. All patients also receive 4 to 7 ribavirin capsules daily as well as a pegylated interferon injection.

Following the drugs approval, Prime Therapeutics’ total per-member-per month costs for treating hepatitis C have increased 31%, according to Dr. Shafer. He said the company is managing the disease through prior authorization, in which only people with genotype 1 disease, documented cirrhosis, and other factors receive telaprevir or boceprevir. Other management strategies for hepatitis C include benefit tiering and specialty pharmacy distribution.

“[Hepatitis C] is a natural fit in making sure you are selecting the right patients,” Dr. Shafer said.

Although many people with hepatitis C are unaware they have the disease, identifying the disease may soon be easier. In August 2012, the Centers for Disease Control and Prevention (CDC) recommended 1-time hepatitis C testing for all people born between 1945 and 1965, a group that accounts for an estimated 27% of the population and 75% of people with hepatitis C.

If more patients are found to have hepatitis C, some will likely soon receive different regimens, as several drugs are in late-stage trials. Dr. Shafer noted that Prime Therapeutics data has said the claims for telaprevir or boceprevir have declined in recent months, and he hypothesized that physicians may be waiting for the new agents to gain FDA approval.

Pamela Belperio, PharmD, a clinical pharmacist at the U.S. Department of Veterans Affairs, said there are 5 hepatitis C drugs in phase 3 development: (1) simeprevir, (2) faldaprevir, (3) vaniprevir, (4) daclatasvir, and (5) sofosbuvir.

Janssen Biotech, Inc., manufacturer of simeprevir, announced on March 28 that it had submitted a new drug application to the FDA for the drug’s approval. It is a once-daily capsule used in combination with pegylated interferon and ribavirin to treat genotype 1 hepatitis C.

Gilead, manufacturer of sofosbuvir, submitted a new drug application to the FDA on April 8 for the drug’s approval. It is an oral medication used in combination with ribavirin to treat patients with genotype 2 and 3 hepatitis C.

Dr. Belperio said several other drugs could be approved and noted there are 370 registered clinical trials for new hepatitis C treatments. The regimens typically fall into 3 categories, according to Dr. Belperio: (1) a direct-acting antiviral plus pegylated interferon and ribavirin (triple therapy); (2) 2 direct-acting antivirals plus pegylated interferon and ribavirin (quadruple therapy); and (3) all-oral regimens that do not require a pegylated interferon injection.

The future options will have several advantages, according to Dr. Belperio, including that they are simplified (once- or twice-daily dosing and shorter treatment duration), they appear to be associated with fewer adverse events, and they have shown in trials to be highly efficacious. However, she cited some possible limitations such as the potential for toxicity, the uncertainty on whether they are effective in patients with cirrhosis or renal insufficiency, the unknown costs of the drugs, and whether they will be reimbursed.