The data might have come too late to win a presentation slot at the ongoing American Academy of Neurology (AAN) conference, but talk on the sidelines is likely to turn to highly encouraging results from the first phase III study of Biogen Idec’s oral MS therapy, BG-12.
Top-line results released today reveal that BG-12 significantly reduced relapses compared to a placebo pill, meeting both primary and secondary endpoints of the trial. Importantly, these endpoints were met by both twice and three times a day doses – hopes were low for the twice a day regimen so these data could signal the drug is better positioned against the new once-a-day therapies than previously thought (Event – Biogen’s MS pill has high bar to cross, February 18, 2011).
Despite clear potential in a disease that sorely needs new treatments, enthusiasm for BG-12 has been capped by its dosing disadvantage. Even if it successfully reaches the market, the drug will face formidable competition from therapies with more convenient once-a-day dosing schedules - Novartis’ Gilenya and quite possibly Teva’s laquinimod and Sanofi-Aventis’ teriflunomide.
Having not trialled a twice a day dose at the phase II stage – the studies used the drug once or three times a day – few were counting on this regimen working in pivotal studies. This unexpected result, alongside what looks like strong efficacy and manageable safety, helped boost Biogen Idec shares 5% in early trade to $76.90 – a three-and-a-half year high.
Headline results were released from a study called Define, which recruited 1,200 patients with relapsing and remitting multiple sclerosis.
BG-12 dosed at 240mg, administered either twice or three times a day, demonstrated a highly statistically significant reduction in the proportion of patients who relapsed at two years compared with placebo, the primary measure. Both doses also met all of the secondary study endpoints, providing a significant reduction in annualised relapse rate, in the number of new or newly enlarging T2 hyperintense lesions, in new gadolinium-enhancing (Gd+) lesions, and in the rate of disability progression as measured by the Expanded Disability Severity Scale (EDSS) at two years.
Safety and tolerability was also encouraging – with events similar among both arms, and consistent with previous studies.
One crucial unanswered issue that remains is the difference between the two doses. Mark Schoenebaum, an analyst with ISI Group, commented today that he believes there may not be much between them, which would be a big win for Biogen. However, if it emerges the three times daily outperformed substantially, the twice daily dose would not be commercially viable, he cautioned.
This detail is now keenly awaited, along with more information on efficacy and safety, in particular drop out rates.
BG-12 has always been viewed as a relatively safer drug than the likes of Gilenya, Tysabri and laquinimod, which suppress the immune system. Generically known as dimethyl fumarate, it is thought the Nrf2 transcription factor protects the nerves from damaging radicals released during the inflammatory process. In fact this more benign side effect profile means many believe the drug’s real potential lies as an add-on therapy to agents like Avonex and Copaxone.
Of course, BG-12’s effectiveness relative to other agents is also hugely important, again more complete data are needed and these will not be available until later in the year. With full laquinimod data due later this week at the AAN conference, BG-12 will not only be held up against Avonex and Gilenya, but a growing list of new oral agents (AAN - Laquinimod MS data to take centre stage, April 7, 2011).
Also due in the second half are data from a second phase III study called Confirm, which uses Teva’s Copaxone as an active comparator.
So by the end of the year the profile of this product will be better known.
In terms of commercial potential not all analysts are including sales forecasts in their models yet so consensus is low - EvaluatePharmadata has sales of $150m by 2016 following a launch in 2012 - but many believe the drug has blockbuster potential.
Although firm conclusions cannot be drawn without further detail, this encouraging kick off to phase III data means forecasts are likely to head higher.