Delayed MS Drugs Awaits Decision at FDA

In March, Biogen learned the FDA would delay its decision on its peginterferon Beta-1a drug, also known as Plegridy, by three months when the agency announced it was extending the initial Prescription Drug User Fee Act date. Here, we talk with Kate Dawson, MD, Vice President of Global Medical – Neurology, about that decision and the data Biogen released at the AAN annual meeting in Philadelphia.

At last year’s annual meeting, Biogen announced that compared to placebo, Plegridy reduced the annual relapse of patients with multiple sclerosis by 36 percent and reduced the proportion of patients who relapsed by 39 percent in its first year results. Was the data released at this year’s meeting similar in year two?

Yes, the second year results of the ADVANCE study confirm what we’ve seen in Year 1. In patients receiving continuous dosing, the efficacy of Plegridy dosed every two weeks was maintained throughout the second year with a safety and tolerability profile in Year 1 consistent with Year 1. Results over two years support the maintained benefit of Plegridy beyond Year 1, with a continued a positive effect on relapses and disease progression.

What were the significant results of year two of the ADVANCE clinical trial? What was presented at this year’s annual meeting in Philadelphia?

Plegridy was featured in three platform presentations at AAN. One highlighted the ADVANCE Year 2 Data, and the other two were post-hoc analyses of Year 1 results versus placebo—the effect on Recovery from Relapse and Freedom from Measured Disease Activity (FMDA), respectively.

As mentioned, Year 2 results of the ADVANCE study showed that the efficacy of Plegridy continuously dosed every two weeks was maintained in the second year of treatment and the safety and tolerability profile was consistent with Year 1.

Relative to Year 1, the annualized relapse rate (ARR) was further reduced and the number of new or newlyenlarging T2 lesions was numerically lower in Year 2.

• The safety and tolerability profile of Plegridy was consistent in Year 1 and Year 2.

Biogen Idec presented additional post-hoc Year 1 data from ADVANCE, which showed that a significantly higher proportion of patients taking Plegridy every two weeks achieved FMDA as measured by no new relapses or confirmed disability progression (Clinical-FMDA) and no new gadolinium-enhancing or new/newly enlarging T2-hyperintense brain lesions (MRI-FMDA) over the first year compared to placebo.

• The proportions of patients with clinical-only, and MRIonly FDMA were significantly higher with Plegridy dosed every two weeks compared to placebo over the first year.

The second analysis of the Year 1 ADVANCE data demonstrated treatment with Plegridy was associated with improved recovery from relapses compared to placebo (as measured by the proportion of patients with a relapse associated with sustained disability progression):

• Following a recent relapse, a lower proportion of patients receiving Plegridy had sustained 12-week sustained disability progression when compared to placebo (14 percent for every two-week dosing, 20 percent for placebo) resulting in a 30 percent relative reduction in the portion of relapses for the every two-week dosing compared to placebo.
• Plegridy was associated with improved recovery from relapses compared to placebo. Plegridy reduced the number of patients experiencing sustained 12-week disability progression due to incomplete recovery following a relapse vs. placebo by 56 percent in the every two-week dosing arm (p=0.012).

Earlier this year the Food and Drug Administration extended the initial Prescription Drug User Fee Act date for Plegridy by three months. Were any solicited or unsolicited amendments made to the original NDA? Did FDA give reasons why they extended the PDUFA date?

Standard 3-month FDA extensions to the PDUFA date are not uncommon, and have been applied to many of the recent NDA reviews for drugs for the treatment of multiple sclerosis. The FDA indicated that the extension of the PDUFA date is needed to allow time for full review. We are working with the FDA to help facilitate the review and the agency has not asked for additional studies.

Given the recent traction made by oral therapies, why do you feel Plegridy will be a good option for MS patients? What does your data show regarding patient compliance?

MS is a highly complex disease that impacts each individual differently. It is important to have a variety of treatment options, including Plegridy, that address individual patient needs. If approved, Plegridy will be the first pegylated interferon for the treatment of MS, offering a combination of efficacy across key disease measures (e.g., disability progression, reduction in relapses, number of MS lesions), a favorable safety profile and a low frequency dosing regimen.

ADVANCE Year 1 data showed that treatment compliance (number of doses a patient received divided by the number they were expected to have) was greater than 99 percent in all treatment groups.