FDA Approves Simeprevir + Sofosbuvir Combination for Hepatitis C


The U.S. Food and Drug Administration (FDA) this week announced additional approval of interferon-free oral therapy for chronic hepatitis C combining Janssen's HCV protease inhibitor simeprevir (Olysio) plus Gilead Sciences' HCV polymerase inhibitor sofosbuvir (Sovaldi), both of which were approved separately in late 2013.

Simeprevir and sofosbuvir were initially each approved for use in combination with pegylated interferon and ribavirin for people with hepatitis C virus (HCV) genotype 1. Yet with many patients and providers seeking all-oral regimens without poorly-tolerated interferon, experts with the American Association for the Study of Liver Diseases (AASLD) and Infectious Diseases Society of America (IDSA), as well as a guidelines panel of the European Association for the Study of the Liver (EASL) included the off-label combination of simeprevir plus sofosbuvir for patients who could not tolerate -- or, in practice, were unwilling to take -- interferon.

The Phase 2 COSMOS trial showed that simeprevir and sofosbuvir work well together without interferon or ribavirin, curing more than 90% of treatment-naive and previously treated genotype 1 patients with or without cirrhosis. Janssen requested approval for this added indication earlier this year.

While evidence supports the efficacy of simeprevir plus sofosbuvir, cost will likely be a barrier. As separate drugs, simeprevir and sofosbuvir are priced at approximately $66,000 and $84,000, respectively -- or a combined cost of $150,000 for a 12-week course (some patients will need 24 weeks). Since then, the FDA has approved Gilead's sofosbuvir/ledipasvir coformulation (Harvoni), which is also highly effective. Priced at $94,500 for a 12-week course -- with an 8-week course adequate for many patients -- Harvoni considerably undercuts simeprevir plus sofosbuvir. Both Janssen and Gilead offer payment assistance programs for their drugs.

Below is an edited excerpt from a Janssen press release announcing the supplemental FDA approval.

OLYSIO (simeprevir) Gains Additional FDA Approval as Once-Daily, All-Oral Interferon- and Ribavirin-Free Treatment Option in Combination with Sofosbuvir for Adults with Genotype 1 Chronic Hepatitis C Infection

Expanded indication includes both treatment-naive and treatment-experienced adult patients with or without cirrhosis

Titusville, N.J. -- November 5, 2014 -- Janssen Therapeutics, Division of Janssen Products, LP (Janssen) announced the U.S. Food and Drug Administration (FDA) has approved OLYSIO (simeprevir), a hepatitis C virus (HCV) NS3/4A protease inhibitor, in combination with sofosbuvir as an all-oral, interferon- and ribavirin-free treatment option for genotype 1 chronic hepatitis C (CHC) infection in adult patients as part of a combination antiviral treatment regimen. Sofosbuvir is an HCV nucleotide analog NS5B polymerase inhibitor developed by Gilead Sciences, Inc.

HCV is a blood-born infectious disease of the liver that affects an estimated 3.2 million people in the U.S. Approximately 75 to 85 percent of people who become infected with HCV develop chronic infection. Most persons with CHC infection are asymptomatic, which means they do not show symptoms of the disease. When left untreated, CHC infection may cause significant liver damage, including cirrhosis, which is severe scarring of the liver. CHC may also increase the risk of developing complications from cirrhosis, which may include liver failure.

Data supporting the OLYSIO and sofosbuvir combination regimen are from the COSMOS study, an open-label, randomized Phase 2 clinical trial that investigated the efficacy and safety of 12 or 24 weeks of OLYSIO (150 mg once daily) in combination with sofosbuvir (400 mg once daily) with or without ribavirin in HCV genotype 1 chronically infected treatment-naive and treatment-experienced adult patients with compensated liver disease.

"It's a very encouraging time for patients with chronic hepatitis as the advent of new direct-acting treatment combinations, like OLYSIO plus sofosbuvir offer all-oral, interferon- and ribavirin-free treatment options," said Eric Lawitz, MD, primary investigator for the COSMOS clinical study, and vice president, Scientific and Research Development, The Texas Liver Institute and professor of medicine, University of Texas Health Science Center. "The availability of multiple treatment options is important to physicians and patients so optimal treatment decisions can be made, given the complexity of the disease and diversity of patient population."

"I lived with hepatitis C for nearly thirty years," said Norman Walsh, a COSMOS clinical trial patient. "I will never forget the moment that my clinical trial healthcare team told me the news following my treatment with the combination of OLYSIO and sofosbuvir. I was elated, relieved -- and cured."

OLYSIO in Combination with Sofosbuvir in HCV Adult, Genotype 1 Patients

The recommended treatment duration of OLYSIO with sofosbuvir is 12 weeks for patients without cirrhosis or 24 weeks for patients with cirrhosis.

The data for this expanded indication are based on two cohorts in the COSMOS study, published in The Lancet. Cohort 1 included prior non-responder patients (patients who failed prior interferon-based therapy) with no to moderate liver fibrosis (defined as METAVIR F0 to F2 scores), and Cohort 2 included treatment-naive patients (patients who have not received other treatments previously) and prior non-responder patients to peginterferon-alfa and ribavirin near cirrhosis (METAVIR F3) and with cirrhosis (METAVIR F4). METAVIR scores measure the severity or stage of liver fibrosis, from early to advanced.

In pooled analyses of both cohorts, 95 percent of patients (20/21) with METAVIR F0-F3 receiving 12 weeks of OLYSIO with sofosbuvir achieved sustained virologic response (SVR12) or cure, the absence of HCV detected in the blood 12 weeks after the end of treatment. Viral relapse occurred in 5 percent (1/21) and 0 percent (0/20) of patients with METAVIR F0-F3 after 12 or 24 weeks of combination therapy, respectively. Regardless of whether patients were treatment-naive or treatment-experienced, 86 percent of patients (6/7) with METAVIR F4 receiving 12 weeks of OLYSIO in combination with sofosbuvir achieved SVR12, while 100 percent of patients (10/10) with cirrhosis who were treated with the combination for 24 weeks achieved SVR12. Viral relapse occurred in 14 percent (1/7) and 0 percent (0/10) of patients with cirrhosis after 12 or 24 weeks of combination therapy, respectively.

For all patients in the COSMOS trial (treatment-naive and treatment-experienced, METAVIR F0-F4), 93 percent (26/28) achieved SVR12 after 12 weeks and 97 percent (30/31) achieved SVR12 after 24 weeks of treatment. Viral relapse occurred in 7 percent of patients (2/28) after 12 weeks and 0 percent of patients (0/30) after 24 weeks of treatment overall.

In the COSMOS trial, the most common (>10 percent) adverse reactions reported during 12 weeks of treatment with OLYSIO in combination with sofosbuvir without ribavirin were fatigue (25 percent), headache (21 percent), nausea (21 percent), insomnia (14 percent), and pruritus (11 percent). Rash and photosensitivity were reported in 11 percent and 7 percent of patients, respectively. During 24 weeks of treatment with OLYSIO in combination with sofosbuvir, dizziness (16 percent), and diarrhea (16 percent) were also commonly reported.

Prior to initiation of treatment with OLYSIO with sofosbuvir, screening patients infected with HCV genotype 1a for the presence of virus with the NS3 Q80K polymorphism is not strongly recommended but may be considered.

Janssen is continuing its clinical development program for OLYSIO, including Phase 3 study commitments. For more information please visit www.clinicaltrials.gov.

"We're pleased that an interferon-free, ribavirin-free OLYSIO-based combination is now approved in the United States for patients with genotype 1 chronic hepatitis C infection. The availability of multiple treatment options is important to help offer an opportunity for cure and we believe OLYSIO will play a meaningful role in this respect," said Gaston Picchio, PhD, hepatitis disease area leader, Janssen Research & Development, LLC. "We're passionate about finding new treatment options for patients living with hepatitis C worldwide and will continue to pursue innovative approaches to help address this disease."

Access and Support for OLYSIO

Janssen partners with a variety of stakeholders to support patient access and compliance to medicines. A substantial part of this effort is working closely with public and private payers to ensure that patients who need OLYSIO can obtain access to it.

For patients, Janssen offers OLYSIO Support, a comprehensive support program designed to assist in the HCV treatment journey so that they, their caregivers and their healthcare providers can help them focus on treatment. OLYSIO Support provides benefit verifications, assistance with the prior authorization process, and information about a variety of affordability programs, including those for patients with commercial insurance, federally-funded insurance or no insurance coverage.

Eligible patients with commercial insurance coverage for OLYSIO may pay only $5 per fill with the OLYSIO Savings Card. This is subject to a $50,000 annual maximum benefit or 12 months from the card activation date, whichever comes first. For more information about OLYSIO Support, visit www.OLYSIO.com or call 1-855-5-OLYSIO (1-855-565-9746), 8 a.m. - 8 p.m. (EST), Monday through Friday.

"The approval of OLYSIO in combination with sofosbuvir is welcome news for people living with chronic hepatitis C infection and their families," said Gloria Searson, ACSW, founder and president, Coalition on Positive Health Empowerment (COPE). "As an organization focused on serving people trying to make sense of their HCV diagnosis, we're encouraged by the work Janssen is doing to provide new treatment options and support programs to help patients navigate their journey."

About OLYSIO (simeprevir)

OLYSIO is an HCV NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB and indicated for the treatment of CHC infection as a component of a combination antiviral treatment regimen.

Janssen is responsible for the global clinical development of simeprevir and has exclusive, worldwide marketing rights, except in the Nordic countries. Medivir AB retains marketing rights for simeprevir in these countries under the marketing authorization held by Janssen-Cilag International NV. Simeprevir was approved in September 2013 in Japan, in November 2013 in Canada and the U.S., in March 2014 in Russia, and in July 2014 in Mexico and Australia. In May 2014 simeprevir was granted marketing authorization by the European Commission (EC) (indications vary by market).

For important safety information about OLYSIO, please see the full press release.

For additional information about OLYSIO, please visit www.OLYSIO.com.

Please see full Prescribing Information and Patient Information for more details.

About Janssen Pharmaceutical Companies

At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in hepatitis C, HIV and other infectious diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Headquartered inTitusville, New Jersey, Janssen Therapeutics, Division of Janssen Products, LP, is one of the Janssen Pharmaceutical Companies of Johnson & Johnson. Visit www.JanssenTherapeutics.com for more information and follow us on Twitter at @JanssenUS.



Janssen Therapeutics. OLYSIO (simeprevir) Gains Additional FDA Approval as Once-Daily, All-Oral Interferon- and Ribavirin-Free Treatment Option in Combination with Sofosbuvir for Adults with Genotype 1 Chronic Hepatitis C Infection. Press release. November 5, 2014.

R Klein, K Struble, and S Morin, U.S. Food and Drug Administration. FDA Hepatitis Update: Changes to Olysio (simeprevir) label. November 5, 2014.