J&J Building Case For Co-Administration Of Olysio With Gilead’s Sovaldi

Launched in the U.S. in 2013, Olysio brought in $354 million in worldwide sales during the first quarter, including $291 million in the U.S. Now, J&J will undertake a pair of Phase III trials that could back an sNDA to add co-administration with Sovaldi to the drug’s labeling.

Having just presented impressive Phase II data supporting use of its hepatitis C drug Olysio (simeprevir) in combination with Gilead Sciences Inc.’s market-leading Sovaldi (sofosbuvir) at a liver disease meeting in Europe, Johnson & Johnson is moving forward with a two-study Phase III program investigating the two agents in HCV patients with and without cirrhosis.

The firm is hearing reports that Olysio frequently is being co-administered with Gilead’s Sovaldi in clinical practice. The combination is advocated in treatment guidelines already, but J&J believes getting the data in labeling is an important next step. J&J unveiled the positive results from the Phase II COSMOS program testing the second-generation protease inhibitor Olysio with Gilead’s nucleoside polymerase inhibitor last week at the European Association for the Study of the Liver annual meeting.

Olysio was among several new products helping to spur a 10.8% year-over-year increase in pharmaceutical sales for a $7.5 billion total for the first quarter, J&J reported April 15. Olysio obtained FDA approval last November and also is on the market in Canada, Japan and Russia, while Europe’s Committee for Medicinal Products for Human Use adopted a positive opinion for marketing authorization of the drug on March 20 (Also see "Simeprevir Clears FDA, But Tougher Road Lies Ahead" - Pink Sheet, 24 Nov, 2013.).

Olysio yielded $354 million in worldwide sales during the first three months of 2014, its first full quarter on the market. Of that, $291 million in sales occurred in the U.S. market. J&J listed Olysio as one of four newer drugs that helped drive the strong quarter – the others were the prostate cancer drug Zytiga (abiraterone acetate) with $229 million U.S. ($512 million worldwide) for the period, the anticoagulant Xarelto (rivaroxaban) with $319 million in the U.S. and the type 2 diabetes drug Invokana (canagliflozin). J&J did not provide a specific sales total for Invokana.

In infectious disease, the pharma also reported a 46.9% decrease year-over-year to $86 million in ex-U.S. sales of Incivo (telaprevir), a first-generation protease inhibitor for HCV that it markets in Europe under a contract with Vertex Pharmaceuticals Inc. However, thanks in large part to Olysio’s strong launch, J&J posted 47.2% growth in worldwide sales of infectious disease drugs during the quarter, from $815 million in first-quarter 2013 to $1.2 billion.

During the firm’s April 15 investor call, J&J CFO Dominic Caruso admitted that Olysio’s performance out of the gate had exceeded the company’s expectations. He cited HCV treatment guidance issued in January by the American Association for the Study of Liver Diseases, the Infectious Diseases Society of America and the International Antiviral Society-USA as one of the factors behind the strong launch (Also see "Sovaldi Is Go-To Drug For HCV; Treatment Guidelines Recommend Off-Label Use" - Pink Sheet, 3 Feb, 2014.).

“The Liver Society issued guidelines in January recommending the use of Olysio along with … Sovaldi,” Caruso noted. “And that has been adopted by the community, by the medical community, as a standard of care,” he said. “That’s something that we learned after our [sales] guidance. We saw it take off and we are very pleased with the results. And if you look at the total increase in our sales guidance, which is about roughly $1 billion, I would say the majority of that is due to the fact that Olysio now is performing much better than our earlier expectations and we're very pleased with that.”

Solid Results In Fibrotic Patients

On April 2, J&J affiliate Janssen Pharmaceuticals Inc. announced that it had begun recruiting patients for the two-trial OPTIMIST program to continue testing a daily combination of simeprevir 150 mg and sofosbuvir 400 mg in HCV. At the EASL conference April 12 in London, Janssen unveiled new data from its Phase II COSMOS program studying the two agents together. Ninety-three percent of genotype 1 HCV patients with advanced liver fibrosis achieved sustained virologic response 12 weeks after the conclusion of therapy (SVR12) in a cohort 2 arm that did not include ribavirin.

The pair co-administered with ribavirin also produced a 93% SVR12 rate in the cohort’s overall population, but several subgroups showed better results using the two new direct-acting antiviral agents without ribavirin. Genotype 1a patients with the Q80k polymorphism achieved a 100% SVR12 rate with the two drugs, compared to 88% who received the combination with ribavirin, for example. However, in patients without the Q80k polymorphism, the SVR12 rate was 93% for patients who got ribavirin with simeprevir and sofosbuvir, but 88% for those who got the two without ribavirin.

Patients with the Q80k polymorphism previously had posted significantly lower cure rates in clinical trials testing Olysio with the old standard-of-care backbone of ribavirin and pegylated interferon. The new COSMOS data indicate that dosing sofosbuvir with simeprevir produces an effect to overcome that issue.

For genotype 1b patients in the cohort, the SVR12 rate was 100% in both dosing arms. However, in genotype 1 patients revealed in genetic testing to have the IL28B CT polymorphism, the cure rate was 100% without ribavirin and 93% with ribavirin. In the harder-to-treat IL28B TT allele patients, the cure rate was 100% without ribavirin and 88% with. Finally, for patients with the most advanced fibrosis (METAVIR 4), the two-drug regimen produced an 86% SVR12 rate, while the tandem with ribavirin produced a 91% cure rate.

Despite the variations in those findings, J&J has decided to run the OPTIMIST program without any dosing of ribavirin. OPTIMIST 1 will test simeprevir 150 mg/sofosbuvir 400 mg daily in about 350 treatment-naïve and treatment-experienced genotype 1 HCV patients without cirrhosis, with dosing periods of eight weeks and 12 weeks, Gaston Picchio, Janssen’s Hepatitis Disease Area Leader, said in an interview. In OPTIMIST 2, the company will dose the two agents over 12 weeks in roughly 100 cirrhotic patients.

J&J’s goal is to build evidence for the use of simeprevir with sofosbuvir, Picchio explained, as the company understands many physicians already have begun doing so even though co-administration with sofosbuvir is not explicitly included in the FDA labeling for Olysio. Sofosbuvir already is being dosed for only eight weeks in some HCV patients, so data showing efficacy for simeprevir/sofosbuvir tandem might add to the combo’s momentum.

“There’s general language that suggests that [Olysio] can be used with other agents – it doesn’t specifically say direct-acting antivirals – but there’s no specific labeling around the use of simeprevir with sofosbuvir,” he explained. “We wanted to show our commitment to the field by running these two Phase III studies to provide additional data on the use of these two agents. So far, the COSMOS data have shown very good safety and efficacy results but we recognize that the sample size is somewhat limited, 167 patients, and we just want to provide additional data.”

FDA’s granting of an indication without a specific reference to HCV combinations was viewed as an attempt at leaving flexibility in a fast-changing market (Also see "How Sovaldi Won A Broad Label: Emerging Data Swayed Reluctant FDA" - Pink Sheet, 19 Mar, 2014.).

An sNDA based on positive results from the OPTIMIST trials is possible, Picchio added. J&J does not have specific numbers on how frequently the two drugs are being used together to treat HCV, but it expects physicians will begin reporting results from their own clinical practice using the agents together at this fall’s AASLD conference, slated for Nov. 7-11 in Boston.

“I think that will be extremely valuable because clinical trial data are one thing, and real live experience is another,” he said. “The fact that physicians are using this combination will allow them to generate real-life data and I’m sure they’ll be reporting it. I’m hearing a lot about that.”

Picchio added that he anticipates some of the physician-reported data will measure treatment response in patients more difficult to treat than those included in the COSMOS protocols.