The competitive profile of Biogen Idec Inc.'s BG-12 in the highly coveted and burgeoning market for oral multiple sclerosis drugs got a big boost April 21 with the release of better-than-expected additional monotherapy data from the Phase III DEFINE study.

In the trial of about 1,200 patients with relapsed, remitting multiple sclerosis, a twice-daily dose of Biogen's candidate demonstrated a 49% reduction in the number of patients who relapsed at two years, meeting the trial's primary endpoint. It also cut annualized relapse rates by 53%, an important secondary endpoint, the company said April 21.

Given that Biogen had revealed April 11 that the trial met all of its primary and secondary endpoints, analysts were prepared for positive news. But the drug's efficacy, coupled with its robust safety profile, surprised even the most bullish analysts. Calling the data "stellar," UBS Investment Research analyst Matthew Roden said the results "far exceed expectations and are much better than competing oral MS drugs."

Investors reacted quickly, sending Biogen's stock price up 15% to a year-long high of $99.70 on the positive news.

Worth some $10 billion and dominated by injectables, the MS market is highly attractive and the market is opening up following the launch of the first oral MS treatment for general use - Novartis AG's Gilenya (fingolimod) - this past fall ([See Deal]).

BG-12 is one of six new MS drugs slated for Phase III releases in the next two years, and results are being closely scrutinized for commercial implications ([See Deal]).

A dimethyl fumarate, BG-12 is believed to activate the Nrf2 transcriptional pathway, a central mechanism of cellular defense. As such, its usage may prevent further cell damage and tissue loss that can cause symptoms in patients, according to the company.

Beating Efficacy Expectations

The DEFINE trial tested a 240 mg dose of BG-12, given either twice or three times daily, against placebo. On April 21, the company provided specific data for the twice-daily regimen only. This dose was shown to reduce the number of patients who relapsed at two years by 49% - the primary endpoint - and cut annualized relapse rates by 53%, a secondary endpoint.

The regimen proved potent on other important secondary endpoints, demonstrating reduction of risk of disability progression, as measured by the expanded disability status scale (EDSS), by 38%. And on MRI scans, it cut the number of new or newly enlarging T2 hyperintense lesions by 85% and gadolinium enhancing lesions by 90%.

While it's not scientifically valid to compare results across trials, the release prompted the usual comparisons against the approved Gilenya as well as other drugs in development.

The BG-12 results are similar to those achieved by Gilenya, which had an ARR of 54% at a 0.5 mg dose and 60% at a 1.25 mg dose, noted Lazard Capital Markets analyst Joel Sendek in a same-day note.

Gilenya has a strong efficacy profile but with serious safety strings attached, including slowing heart rate, infections, macular edema, breathing and liver problems. Hence, its approval came with a Risk Evaluation and Mitigation strategy, leaving room for competitors that can show a milder profile (Also see "Novartis Gilenya Approved With Advisory Panel-Enhanced REMS" - Pink Sheet, 22 September, 2010.).

Safety specifics from DEFINE are not available, but Biogen execs said that the profile is on par with data from Phase II studies. Adverse events that had emerged in previous trials included flushing and GI effects. Conversations with physicians suggest that "many do not see these effects as impediments to BG-12's adoption," observed Bernstein Research analyst Geoffrey Porges in a same-day note.

Previously released data for BG-12 had suggested a superior safety and tolerability profile to Gilenya and, consequently, Biogen's drug "could become the leading oral MS therapy," Sendek concluded.

Baird's Christopher Raymond also hailed the efficacy data but cautioned that full safety data are yet to be presented and have important commercial implications. Hence, in his view, the market uplift may be overdone.

Moreover, Gilenya does have a once-daily dosing advantage that could prove to be an important competitive advantage over twice or three times daily dosing for BG-12.

Vital Head-to-Head Results To Come

Following the release of DEFINE data, results from a second PHASE III study called CONFIRM, which tests BG-12 against Teva Pharmaceutical Industries Ltd.'s first-line injectable Copaxone (glatiramer), are eagerly awaited and will become available in the second half of this year.

During an April 21 investors' call, Doug Williams, executive vice president of R&D, said that if the CONFIRM data are consistent with what has been reported to date, the company will file for approval "as quickly as possible, possibly early next year."

The study against Copaxone will become the ultimate reference point for judging BG-12's efficacy, but the "current results position BG-12 to potentially move ahead in the race for a safe oral alternative," wrote Porges.

In addition to Gilenya, BG-12's main rivals include Teva's oral laquinimod. This month, Teva announced Phase III ALLEGRO results, revealing laquinimod met its primary annualized relapse rate endpoint as well as secondary endpoints. Still the data were viewed as lackluster given laquinimod reduced the ARR by only 23%, while cutting EDSS by a modest 36% ([A#14110421008]).

In a survey conducted in late January by "The Pink Sheet" sister publication In Vivo and the Gerson Lehman group, neurologists said that they were very aware of the drugs in late-stage development ([See Deal]). More than 60% said that they would consider using laquinimod and other drugs in the pipeline, but only 48% said that they expected to prescribe BG-12. However, respondents said that they needed more data to base decisions upon and DEFINE and ALLEGRO have the potential to sway their opinions.

Interviews with physicians had indicated that most physicians expected BG-12 efficacy results to be lower, so the data just reported represent upside, Porges noted.

- Emily Hayes (e.hayes@elsevier.com)

Biogen Idec's BG-12 Results Up The Ante In The Oral MS Market

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