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Biogen Idec's MS Therapy Yields Positive Results in Phase III

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By Catherine Shaffer
Staff Writer

Biogen Idec Inc.'s peginterferon beta-1a produced a significant reduction in annualized relapse rate in patients with multiple sclerosis according to primary efficacy analysis from a Phase III study. The drug also met its secondary endpoints of reducing risk of 12-week confirmed disability progression and proportion of patients relapsed. The study brings the possibility of interferon dosing every two weeks or four weeks a step closer to reality for patients with relapsing-remitting multiple sclerosis.

According to the Weston, Mass.-based company, patients have differing responses to therapies for relapsing-remitting multiple sclerosis, and therefore a greater range of choices will improve options for patients.

"What we have seen over the last two decades, is first a big change when interferons were approved for treatment of multiple sclerosis, and more recently improvement when a whole slew of other drugs were approved. Patients have gone from no choices to a number of options and choices. Choices are important for patients," Gilmore O'Neill, vice president, global neurology late stage clinical development, told BioWorld Today.

The two-year Phase III ADVANCE trial tested peginterferon beta-1a in 1,516 randomized patients with the disease. The drug was administered by subcutaneous injection on a once-every-two weeks or once-every-four-weeks schedule. For the two-week dosing group, the annualized relapse rate (ARR) reduction compared to placebo was 35.6 percent (p < 0.001) and the four week dosing group had an ARR of 27.5 percent (p < 0.02).

The risk of 12-week confirmed disability progression as measured by the Expanded Disability Status Scale was improved by 38 percent in both dosing arms, and the proportion of patients who relapsed was reduced by 39 percent in the two-week dosing group, and 26 percent in the four-week dosing group.

Researchers also looked at the number of new or newly enlarging T2-hyperintense lesions on brain MRI scans, and found that those were reduced 67 percent compared to placebo in the two-week dosing group, and 28 percent in the four-week dosing group. Safety and tolerability profiles were favorable for both dosing regimens, with rates of adverse and severe adverse events similar in both groups. Redness at the injection site and influenza-like illness were the most commonly reported events.

Interferons have been used in multiple sclerosis for some time with good effect, although the exact mechanism of its action on the disease is unknown.

Peginterferon beta-1a is a pegylated form of Biogen Idec's successful drug Avonex (interferon beta-1a). The pegylation of the product is intended to prolong the half-life to enable less frequent dosing.

Biogen Idec's commitment to multiple sclerosis runs deep. In addition to Avonex, it markets Tysabri (natalizumab) for relapsing forms of multiple sclerosis in the U.S. and for relapsing-remitting MS in the European union.

It is also developing Fampyra (fampridine) to improve walking ability in adults with multiple sclerosis, and BG-12 (dimethyl fumarate) for relapsing forms of multiple sclerosis.

There are some concerns regarding the seemingly stronger results for the two-week dosing group.

In a flash comment from Wells Fargo Securities, senior analyst Brian Abrahams wrote, "Though both doses reached statistical significance, one minor disappointment is that the once every two week regimen appears clearly numerically better on most measurements than the once-monthly regimen. . . . We believe adoption would be greater if once-monthly Avonex looked as effective."

O'Neill responded, "We tested both against placebo. We have just gotten the top-line data, and we are very happy. The final selection of dose or dosing regimens will depend on more detailed analyses and is a matter of discussion with regulatory agencies."

ISI Group's Mark Schoenebaum noted that currently approved competing drugs are all injected at least once a week. "Thus, even a twice per month Avonex is a major convenience advance, with once a month being the 'home run' in terms of convenience."

Ian Somaiya, an analyst with Piper Jaffray, was more concerned about the dosing schedule differences. "Based on recent conversations with clinicians, success of once-monthly was critical to keeping patients on Avonex. Once every other week was not perceived to offer enough convenience or safety benefit to prevent switching to orals."