Feds approve two
new hepatitis C meds
by Liz Highleyman
The Food and Drug Administration has approved Gilead Sciences' new hepatitis C drug sofosbuvir (brand name Sovaldi), following the recent approval of Janssen's simeprevir (brand name Olysio). The drugs promise to dramatically improve cure rates – in some cases without interferon – but their high prices may present a barrier to widespread use.
"With the recent approval of Sovaldi and Olysio, we have entered the highly promising hepatitis C treatment era that we've all been waiting for," Ryan Clary, director of public policy for the National Viral Hepatitis Roundtable, told the Bay Area Reporter. "Our priority now is to ensure that all public and private insurers provide immediate access to these lifesaving drugs, and to make sure that everyone with hepatitis C knows about the companies' patient assistance programs."
An estimated 3.2 million people in the U.S. are living with hepatitis C, according to the Centers for Disease Control and Prevention, with the majority being baby boomers born between 1945 and 1965. Over years or decades chronic hepatitis C can lead to serious liver disease including cirrhosis and liver cancer, and it is the leading indication for liver transplants.
"CDC continues to urge every baby boomer in America and others at risk to get tested for hepatitis C," said John Ward, director of the CDC's Division of Viral Hepatitis. "Widespread screening, together with new cures, promises to slash the burden of hepatitis C in this country and save thousands of lives."
The development of direct-acting antiviral agents has brought about a revolution in the treatment of chronic hepatitis C. For many years the standard of care has been pegylated interferon plus ribavirin, which requires up to a year of treatment, causes difficult side effects including flu-like symptoms and depression, and cures fewer than half of people with HCV genotype 1. Because of the difficulty of treatment, many people with hepatitis C and their doctors have been waiting for promising new drugs, especially interferon-free regimens.
The FDA approval for sofosbuvir came December 6. That followed by about a week its approval of simeprevir.
Sofosbuvir (formerly known as GS-7977 and PSI-7977) is the first-ever nucleotide analog HCV polymerase inhibitor. Gilead purchased the drug's initial developer, Pharmasset, in 2011. Simeprevir (formerly TMC435) is a next-generation HCV protease inhibitor discovered by Sweden's Medivir and developed by Janssen (now part of Johnson and Johnson). As with antiretrovirals for HIV, combining drugs that target different steps of the HCV lifecycle improves potency and reduces the risk of drug resistance.
Sofosbuvir and simeprevir are both taken as a single once-daily pill. They produced overall cure rates of around 80 to 90 percent in phase 3 clinical trials, though individual response varies based on several factors including HCV genotype, prior treatment history, and extent of cirrhosis.
Simeprevir was approved as an add-on to interferon-based therapy for people with HCV genotype 1. Triple therapy is used for 12 weeks, followed by pegylated interferon/ribavirin alone for an additional 12 or 36 weeks. It is not yet approved for interferon-free combinations.
Sofosbuvir was approved for use with ribavirin for people with HCV genotypes 2 or 3, making it the first-ever interferon-free hepatitis C treatment. Reflecting the recent realization that genotype 3 is more difficult to treat, recommended duration is 12 weeks for genotype 2 and 24 weeks for genotype 3.
Sofosbuvir was also approved in combination with pegylated interferon and ribavirin for 12 weeks for people with harder-to-treat HCV genotypes 1 or 4. But the FDA said sofosbuvir plus ribavirin without interferon for 24 weeks may be used for genotype 1 patients who are ineligible for or unable to tolerate interferon. The FDA unexpectedly also expanded sofosbuvir's indication to include HIV/HCV coinfected people and patients with liver cancer awaiting transplants.
The current approved indications do not include combining simeprevir plus sofosbuvir in an oral regimen that eliminates both interferon and ribavirin. However, some people with hepatitis C have expressed interest in trying this combination off-label, and it produced a high cure rate in a phase 2 trial. Gilead is currently testing a combination pill containing sofosbuvir plus its HCV NS5A inhibitor ledipasvir.
Price a potential barrier
Janssen set the wholesale acquisition cost of a 12-week course of simeprevir at $66,360. Gilead upped the ante, pricing sofosbuvir at $84,000 for a 12-week course, or $1,000 per pill.
"While we are very excited to have more effective and more tolerable treatment options for people living with hepatitis C, we are concerned about the overall cost of treatment," said Lorren Sandt of the Fair Pricing Coalition. "Treatment is just too costly for the majority of people living with chronic HCV and we fear that barriers to patient access will be inevitable as a result."
"Gilead's predatory pricing of Sovaldi is a direct threat to public health, and it sets the stage for legislators and advocates to demand that officials who purchase drugs for government programs like Medicaid, Medicare, and the AIDS Drug Assistance Programs act decisively to rein in pricing and protect patient access to lifesaving medications," declared AIDS Healthcare Foundation President Michael Weinstein.
The Fair Pricing Coalition worked with Janssen and Gilead to develop patient assistance programs for people who are uninsured, underinsured, or otherwise in need of financial assistance to pay for simeprevir or sofosbuvir.
Janssen's Olysio Savings Program will cover people with incomes up to 500 percent of the federal poverty level, while Gilead's Support Path program offers assistance for people with incomes up to $100,000 for a family of one to three people. Both companies will provide co-pay assistance for people with private insurance who need help paying for out-of-pocket medication costs and covering insurance deductibles. Gilead also said that it is developing a treatment access program focusing on countries with the greatest burden of hepatitis C.
"The approval of sofosbuvir and simeprevir are historic events, both for folks with hepatitis C alone as well as those with HIV/HCV coinfection, where complications from liver failure have emerged as a major cause of suffering and death," Jay Lalezari of Quest Clinical Research told the B.A.R. "These new drugs, along with others in the pipeline, will render hepatitis C easy to treat in most cases and, in their way, are as life-changing as the drugs we use to treat HIV."
Quest is currently enrolling people with hepatitis C and HIV/HCV coinfection for several clinical trials of sofosbuvir as well as experimental regimens from AbbVie (formerly Abbott) and Bristol-Myers Squibb.
"All the studies are now showing sustained response rates in the 90 percent range, so it's really about bringing new drugs to market to force price competition," Lalezari said. "Say what you like about pharmaceutical companies, but in these two arenas, the research effort has been extraordinary."