Medivir AB reported preliminary data from two Phase III studies of simeprevir conducted by partner Janssen R&D Ireland, a unit of Johnson & Johnson (JNJ), suggesting the once-daily NS3/4A protease inhibitor (PI) could additionally benefit individuals with genotype 1 hepatitis C virus (HCV) co-infected with HIV-1 and patients with genotype 4 chronic HCV who have compensated liver disease.

Timing of the findings, reported at the European AIDS Conference in Brussels, was fortuitous: The new drug application (NDA) for simeprevir faces a review by the FDA Antiviral Drugs Advisory Committee (adcom) meeting on Oct. 24.

The open-label trial in 106 HCV/HIV co-infected patients evaluated the safety and efficacy of simeprevir (150 mg) with pegylated interferon and ribavirin (PR) for 12 weeks. Treatment-naïve patients (N = 53) and prior relapsers (N = 15) without cirrhosis received response-guided therapy (RGT) with PR up to 24 or 48 weeks. Previous non-responders, partial responders and patients with cirrhosis received PR up to 48 weeks.

The primary endpoint was sustained virologic response (SVR) rate 12 weeks following treatment. In the study, 93 patients were receiving antiretroviral therapy (ART), 12 percent of patients had cirrhosis, 82 percent had genotype 1a subtype and 73 percent had an IL28B CT or TT genotype.

Medivir, of Huddinge, Sweden, said high SVR12 rates were observed regardless of prior HCV treatment response: 79 percent in treatment-naïve patients, 87 percent in prior relapsers, 70 percent in partial responders and 57 percent in non-responders. Most patients eligible for shorter duration of treatment (89 percent) met the RGT criteria; of these, 87 percent achieved SVR12.

The SVR12 rate was 89 percent in genotype 1b and 70 percent in genotype 1a. Genotype 1a patients with Q80K polymorphism at baseline achieved SVR12 rates of 67 percent. SVR12 rates were high irrespective of baseline Metavair fibrosis score, at 80 percent and 64 percent for patients with of F0-F2 and F3-F4, respectively.

Once-daily simeprevir with PR was well tolerated, with a safety profile similar to that observed in previous studies.

The second Phase III study was similar in design, enrolling 107 patients with chronic HCV genotype 4 who received simeprevir once daily with PR for 12 weeks. Treatment-naïve patients and prior relapsers received RGT with PR up to 24 or 48 weeks, and prior partial responders and prior null responders received PR up to 48 weeks.

At the time of interim analysis, only data from patients eligible for shortened therapy who had reached study visit W28 (SVR4) and W36 (SVR12) were included. These patients achieved SVR4 rates of 89 percent to 91 percent (N = 20) and SVR12 of 67 percent to 100 percent (N = 9). Overall, simeprevir was well tolerated, with most adverse events at grade 1 or 2.

The mature genotype 4 data are expected in the first half of 2014, according to Medivir spokesman Rein Piir.

All Eyes on Two Adcoms

The new data will have little immediate impact on the drug’s prospects in the U.S. In April, Janssen submitted the NDA for simeprevir, which was granted priority review by the FDA for once-daily administration with PR to treat genotype 1 chronic HCV. Once the FDA completes its review and, assuming the drug is approved, Janssen likely will file for a label expansion in the U.S., Piir said.

In May, Janssen-Cilag International NV filed a marketing authorization application for the compound with the European Medicines Agency to treat genotype 1 or 4 HCV. Since that review process has different “clock stops,” the additional Phase III HIV/HCV data could potentially be included to seek a broader label from the outset in Europe, Piir told BioWorld Today.

In September, simeprevir was approved in Japan to treat genotype 1 HCV.

Janssen and its affiliates hold exclusive global rights to the compound outside the Nordic countries, where Medivir retained rights.

Medivir’s shares (STOCKHOLM:MVIRB) enjoyed a 5.5 percent bounce Friday, closing at SEK106.50 (US$16.61). However, analysts already are looking beyond simeprevir’s expected approval to its competitive spot in the HCV market.

In a comparison of the HCV franchises at Gilead Sciences Inc. and Medivir following the Swedish firm’s analyst day on Oct. 10, RBC Capital Markets analyst Michael Yee said Medivir is projecting HCV as “a long-tailed $10-20B market,” encompassing 400,000 patients annually before moderating to 300,000 into 2020. Although such a bullish scenario might benefit Medivir, Yee said, it likely would propel Gilead’s sofosbuvir even farther, beyond consensus projections as a $7 billion drug.

The FDA adcom for sofosbuvir is scheduled for Oct. 25, with a decision on that drug expected Dec. 8. (See BioWorld Today, Nov. 13, 2012, and Feb. 6, 2013.)

In a separate note, Yee suggested the key focus of both adcoms will be on the proposed labels, “particularly for GILD, as they have applied for a very broad indication that says ‘in combination with other agents,’” he wrote. Theoretically, this could include combination with simeprevir, Yee suggested, which as a combined all-oral showed cure rates of up to 100 percent in genotype 1 null advanced patients.

Although a simeprevir launch could be overshadowed by concurrent approval of sofosbuvir – the first interferon-free, all-oral regimen – approval in Japan does gives partner JNJ a head start in the world’s third largest HCV market, Yee added.

In the meantime, earlier this month Janssen acquired Phase II NS5a inhibitor GSK805 from Glaxosmithkline plc, of London. No financial terms were disclosed, but the deal gave Janssen all rights to develop and commercialize the compound, including in combination with other drugs. Janssen said it plans to initiate Phase II studies of GSK805 in interferon-free combinations with simeprevir and TMC647055, Janssen’s non-nucleoside PI.

“The whole point is that JNJ will try to develop an all-oral [possibly once daily] HCV combo to compete against the simplest and easiest,” Yee wrote, including not only sofosbuvir but also drugs in late-stage development at Abbvie Inc., Bristol-Myers Squibb Co. and Merck & Co. Inc.