Roche Will Use REMS Program Data To Show Actemra Is Safe For First-Line RA

Swiss pharma's Genentech unit announced tocilizumab approval for failed TNF patients Jan. 8, saying it is committed to seek earlier uses with post-marketing data, including data from pharmacovigilance and risk plans as well as clinical studies.

Roche's novel interleukin-6 inhibitor Actemra gained FDA approval Jan. 8 for treating patients with moderately to severely active rheumatoid arthritis for whom TNF blockers aren't working - a good beginning but still a ways from the first-line indication the pharma sought and still hopes to gain using data from its risk management programs and other sources.

The Actemra (tocilizumab) Risk Evaluation and Mitigation Strategy includes a Medication Guide, communication plan and timetable for submission of assessments, all intended to ensure patients and physicians fully understand the risks as well as the advantages of the first-in-class drug. But Roche appears to be getting more than a patient safety strategy out of the program.

The Swiss pharma wants to generate data to support approval earlier in RA, including presumably the first-line indication it asked for in its November 2007 BLA (Also see "Roche Files BLA For Rheumatoid Arthritis Therapy Actemra" - Pink Sheet, 21 Nov, 2007.). FDA cleared Actemra with a second-line approval, for use in moderate to severe RA in adult patients who have had inadequate response to one or more TNF antagonists.

To achieve the goal of first-line use, Roche and its South San Francisco, Calif.-based Genentech unit will use data on the clinical benefit and safety of Actemra gained through "our large pharmacovigilance program, including the risk management program, and ongoing clinical and post-marketing studies globally," Hal Barron, executive VP-global development and Roche/Genentech's chief medical officer, said in a written statement.

The REMS comes out of a "complete response" letter FDA issued in September 2008 and then clarified that December (Also see "Roche’s Actemra Delayed By REMS, FDA Study Requirements" - Pink Sheet, 5 Dec, 2008.). In addition to the request for a risk management plan, FDA asked for data on co-developer Chugai's manufacturing facility and for confirmational pre-clinical studies showing Actemra doesn't affect fetal development or fertility, Roche said.

Speaking at the JP Morgan Healthcare Conference in San Francisco Jan. 11, Roche Chief Financial Officer Erich Hunzicker was unfazed by the added complexity brought by the REMS. The product is liked by rheumatologists, and "we get good feedback from patients," he said. Hunzicker predicted Actemra will be a product whose success is built by patient word of mouth. Roche hasn't changed its assumption on Actemra sales or for the label, he said.

Actemra, approved as a monotherapy or in combination with methotrexate or other disease-modifying agents, is an attempt to challenge the RA market currently dominated by TNF-blocking therapies, including Pfizer's Enbrel (etanercept), Abbott's Humira (adalimumab), Johnson & Johnson/Merck's Remicade (infliximab), UCB's Cimzia (certolizumab) and J&J's Simponi (golimumab); the market for the TNF class has been projected to reach nearly $30 billion by 2014 (Also see "Market Snapshot: Anti-TNFs Grow Despite Tough Market" - Pink Sheet, 8 Dec, 2008.).

Tocilizumab, co-developed with Roche's Japanese unit Chugai, has been approved in Japan since 2005. It is marketed in the European Union as RoActemra, with approval in combination with methotrexate and as monotherapy for treatment of the same population as in the U.S.

In October 2009, Roche released two-year results from a fifth Phase III clinical trial of tocilizumab, the LITHE study, which focuses on the antibody's efficacy in prevention of structural joint damage - an earlier setting than the symptom and joint inflammation claims substantiated by the previous Phase III studies. In the LITHE study, patients treated with Actemra plus methotrexate suffered 81 percent less joint damage than those treated with methotrexate alone.

In all, Actemra has been tested in more than 4,000 patients, Roche said. Serious side effects include serious infections that may lead to hospitalization or death, gastrointestinal perforations, and hypersensitivity reaction, including anaphylaxis.

That safety profile is similar to that of the biologically similar TNF class, which also has a REMS requirement. The most common adverse effects were upper respiratory tract infection, nasopharyngitis, headache, high blood pressure and increased liver enzymes that were generally mild and reversible, with no apparent permanent or clinically evident hepatic injury.

Actemra will be available to U.S. prescribers Jan. 18, Roche said.

-Shirley Haley ([email protected])