Rituxan Launch For Arthritis, Tysabri Return Expected In Mid-’06, Biogen Says

Biogen Idec could launch Rituxan (rituximab) for rheumatoid arthritis and relaunch Tysabri (natalizumab) for multiple sclerosis by mid-2006, CFO Peter Kellogg said during an Oct. 26 earnings call.

"As we look ahead to 2006, we expect and have modeled that first Tysabri will be reintroduced in the U.S. in mid-2006 and launched in the EU in the second half of 2006," Kellogg said.

"Secondly we've assumed that Rituxan in RA will be approved and launched by mid-2006."

Biogen and its Rituxan co-development partner, Genentech, submitted the sBLA in late August for use in RA patients who are inadequate responders to TNF inhibitors (¹ (Also see "Genentech Pipeline Puts Firm Ahead Of 2005 Goals, Sailing To “Horizon 2010”" - Pink Sheet, 17 Oct, 2005.), p. 3). The companies requested priority review.

The filing was based primarily on 24-week data from the REFLEX trial.

Study patients who received a single course of two infusions of Rituxan in conjunction with methotrexate demonstrated statistically significant improvement of symptoms at 24 weeks compared to those patients receiving placebo and methotrexate, the companies said.

The most common side effects in the trial included headache, upper respiratory tract infection and nasopharyngitis. Analysis of the trial data did not reveal any unexpected safety signals, according to the companies, and the reported rate of serious adverse events was comparable across treatment arms.

Biogen said it will start to build a separate sales force toward the end of 2005 for the RA indication.

The Rituxan partners also are planning to initiate a global Phase III program in late 2005 or early 2006 in patients who were inadequate responders to one or more disease modifying anti-RA drugs following positive results from the Phase IIb DANCER study.

A Rituxan sBLA for front-line treatment of intermediate-grade or aggressive CD-20 positive, B-cell, non-Hodgkin's lymphoma in combination with chemotherapy is pending at FDA.

"We continue to be excited about the value of Rituxan broadly in autoimmune indications and are investigating its use in lupus...and multiple sclerosis and other areas," Exec VP-Development Burt Adelman said.

On the multiple sclerosis front, the company is anticipating the return to market of Tysabri.

The MS agent was initially approved in November 2004 but withdrawn from the market in February following reports of progressive multifocal leukoencephalopathy in clinical trial patients (² (Also see "Tysabri Withdrawn Pending Analysis Of Safety Signal In Long-Term Trial" - Pink Sheet, 7 Mar, 2005.), p. 3).

Following completion of a safety evaluation of MS patients, Biogen and partner Elan submitted an sBLA seeking to return the therapy to the MS market in September.

The submission includes a risk management plan that calls for a patient registry and an expanded label based on two-year results from the Phase III AFFIRM monotherapy trial and data from the Phase III SENTINEL add-on trial with Avonex (³ (Also see "Tysabri Resubmission: Early Safety Test For New Commissioner" - Pink Sheet, 3 Oct, 2005.), p. 9).

In October, Biogen and Elan announced that a safety analysis of Tysabri in Crohn's and RA patients found no new confirmed cases of PML.

The companies, however, have halted commercial development of Tysabri in RA due to poor efficacy results, Biogen said during its earnings call.

The Tysabri safety reviews encompassed 3,500 patients. "Approximately 91% of eligible clinical trial MS patients chose to participate in the [safety] evaluation, and approximately 88% of the eligible Crohn's disease and RA clinical patients participated," Elan Exec VP-Global R&D Lars Ekman said during the company's Oct. 27 earnings call.

The companies are requesting priority review on the MS resubmission; under a six-month review clock, the user fee date would fall in late March.

FDA reviewers who worked on the original Tysabri application also will be involved in evaluating the resubmission, Elan said.

The Tysabri commercial partners have previously said they expect an advisory committee meeting before the therapy could be returned to market.

Although commercial launch is conservatively estimated to occur by mid-year, Elan is preparing to launch as early as the end of the 2006 first quarter, around the time of the FDA action date.

"We, from a planning point of view, are looking to re-launching Tysabri around the end of the first quarter next year, potentially," Elan CFO Shane Cooke said.

Elan estimates its total commercial and development spend on Tysabri will be $150 mil. in 2006.

These costs include restarting MS patients on Tysabri in a clinical trial.

The firms are currently finalizing protocols for a "re-dosing" trial design with FDA using Tysabri as monotherapy.

"The feedback that we are receiving is that a very high percentage of patients have indicated that they are interested in participating in these trials," Ekman said. "Dosing of the patients is expected in the coming months."

The re-introduction of Tysabri could help spur growth in the U.S. multiple sclerosis market, Biogen said.

"The market growth overall...has slowed a bit in the U.S.," Biogen's Kellogg said.

"As you go forward to next year, we're looking forward to continuing to hold our strong position with Avonex but also get back into reintroducing Tysabri."

"As you look back at the [Tysabri] launch experience of this year, one thing that you have to conclude is that while the U.S. market growth overall had been slowing up to that launch, clearly there is a lot of unmet need out in the market," he said.

U.S. sales of Avonex (interferon beta-1a) increased 5% to $235 mil. in the third quarter. "In the U.S., Avonex remains the market leader with about 40% market share" in the MS category, Kellogg said.