Biogen Idec’s heralded BG-12 will have a coming-out party of sorts at the European MS conference ECTRIMS as full data is unveiled from the Define trial, the results of which have already helped pushed shares in the Massachusetts group to record highs this year (Biogen steals Teva's thunder with BG-12 data, April 26, 2011).
The benign safety profile of the immunosuppressant, fully disclosed in abstracts released yesterday, suggest BG-12 will steal the limelight from the current crop of oral MS agents. Still, the remaining compounds will want to show themselves as more than also-rans in a $13bn market, with data from oral candidates laquinimod and teriflunomide, along with antibodies Lemtrada and daclizumab, all set for scrutiny by MS specialists.
Industry observers are anxiously awaiting the release of BG-12’s second trial, Confirm, which pits it against Teva’s Copaxone, the indication’s biggest seller that loses market exclusivity in 2014 (Event – BG-12 needs to confirm blockbuster potential, September 21, 2011).
In the meantime, news from the Define trial that BG-12 has ticked the safety box came as some relief, as that was the biggest unknown about the fumarate – it has the same active ingredient as anti-psoriasis drug Fumaderm, which requires constant monitoring because it can cause reversible renal dysfunction and other adverse events.
The full data set reveals, however, that BG-12 has “Gilenya-like” efficacy, in the words of RBC analysts, with fewer safety issues. More frequent flushing than placebo in the twice- and three-times-daily arms was the standout result.
Adverse events caused 13% of placebo patients to discontinue therapy, compared with 16% in either BG-12 arm. Infection and severe infection rates were similar between BG-12 and placebo, and importantly for an immunosuppressant no opportunistic infections were reported in the active arms.
This will likely do little to discourage the excitement over BG-12. It started the year with ho-hum 2016 sales forecasts of $129m, but is now pushing the $2bn threshold with the broadly positive results, according to EvaluatePharma.
Biogen’s most valuable product by net present value, its impressive clinical performance has a lot to do with the company's impressive stock market run this year – shares were up 39% in the first nine months of the year, suffering only with the general down market beginning in August (Big pharma resilience tested as stock markets tumble; BMS stands out as gainer after nine months, October 3, 2011).
Rest of the pack
Teva had hoped that laquinimod would help to defend its MS franchise as threats emerge to its intellectual property over Copaxone (Event – Teva needs Copaxone patent victory, August 22, 2011). Laquinimod has disappointed, however, with its Bravo trial failing to significantly reduce patients’ annualised relapse rate – a full reading of the Bravo data has been slated for a late-breaker session at ECTRIMS.
Detailed data from the Allegro trial announced earlier this year will also be outlined; that trial found laquinimod reduced the annualised relapse rate by 27% when compared to placebo, compared with BG-12’s more impressive 53% with twice-daily dosing.
More data from the Temso study of Sanofi's teriflunomide, now dubbed Aubagio, is also due to be read at ECTRIMS. The French company says it has already filed for US approval.
The first data from Temso was announced at ECTRIMS a year ago. At the time, observers compared its efficacy to interferons like Avonex and Rebif, with better safety. With that in mind, the commercial challenge appears to be finding it a niche in the increasingly competitive MS market.
Thus, the relatively benign four-year safety results from a Temso extension, along with analyses of cognitive outcomes and hospital use resulting from that trial will all be viewed as incremental developments. Sanofi has an extensive late-stage clinical programme, including two that complete next year, which could help the product carve out a commercial niche.
Three monoclonal antibodies will be under the microscope at the late-breaker session. Most closely watched will be a readout of data from a phase III trial of Biogen and Abbott Laboratories’ daclizumab, which scored poorly on safety in a trial that reported first data two months ago (Daclizumab dazzles on efficacy but sours on safety, August 10, 2011).
If it turns out that physicians view the infection and liver function signals as tolerable, daclizumab could find its impressive positive effects on relapse and disability rates will help it find its way into more front-line use. It does have a second trial ongoing, so further positive data could reinforce its clinical utility.
Biogen Idec and Elan's Tysabri also has a slot with some long term data, and given the resurgence in demand for the product and efforts to define its safety profile, will be of interest.
Full data from the Care-MS I trial of Lemtrada, the point of contention in Sanofi’s buyout of Genzyme earlier this year, also will be detailed at the late breaker session. The test against Rebif showed reduction in relapses but failed to stave off disability progression, suggesting that it may be the smaller product that Sanofi supposed when it offered Lemtrada-related contingent value rights to Genzyme shareholders during the acquisition (Lemtrada looks unlikely to cost Sanofi much more, July 11, 2011).
However, given the events of the year, it will either take a serious stumble from BG-12 or a substantial improvement in performance by one of its competitors to steal attention away from the Biogen pill.