The oral MS therapy space is about to heat up. Teva and Active Biotech are scheduled to unveil full data on laquinimod at the American Academy of Neurology annual meeting next week, and experts will be watching closely for signs it can match the efficacy of existing therapies, without worrying safety signals.
Detailed laqinimod results will be the most closely watched by experts at the meeting; early MS data from oral competitor teriflunomide, antibody daclizumab and a long-acting form of Avonex will also be of interest. With the failure of Merck KGaA’s Movectro in the US and Europe, MS specialists are looking to the next generation of therapies to improve upon therapies like Biogen Idec’s injectable Avonex and the new kid on the block, Novartis’ Gilenya (Novartis wins strong label for first oral MS pill, September 22, 2010).
Teva and Active have already revealed topline data on laquinimod showing the once-daily capsule met primary and secondary efficacy and safety endpoints against placebo, building hopes it will become a first-line treatment (Dark horse laquinimod reveals potential as MS pill, December 9, 2010). With expectations so high, observers will be watching for any signs that laquinimod might fall short, especially as it is derived from linomide, an experimental drug pulled because of heart attack risk.
The data to be released come from the Allegro trial, which tested laquinimod against placebo. When the partners announced the topline findings, they disclosed little detail other than that the study achieved endpoints of significant reductions in annualised relapse rates and disability progression rates and that adverse event occurrences were similar in both arms; thus an expectation of at least equal efficacy to Avonex and clean safety have been built.
To match injectables a 25-40% reduction in relapse rate needs to be seen, and similar improvements in disability scores – without safety signals. Short of that, the drug will likely be viewed as a disappointment. A second trial called Bravo is expected to report in the third quarter, comparing laquinimod directly with Avonex and providing the clearest picture of its relative efficacy. However, conclusions will be drawn on Bravo's chances of success from the full Allegro data.
Race for second
The MS space will be evolving over the next few years. The four top drugs – Teva’s injectable agent Copaxone, and the interferon class of Avonex, Merck KGaA’s Rebif and Bayer’s Betaferon/Betaseron – all lose patent protection by the end of 2014 and are all expected to lose market share. As a complex biological Copaxone is less vulnerable to generic competition and is expected to hold onto its top position in the indication. Not by much however - consensus for sales in 2016 of $2.84bn is not much above Gilenya’s $2.5bn, according to data from EvaluatePharma.
But an ongoing trend in the field is to make dosing more convenient; hence Biogen emphasises the once-a-week injections of Avonex to the once-daily of Copaxone and the multiple injections per week of other interferons.
Thus the race to develop an oral pill, won by Novartis with once-daily Gilenya; follow-on oral medications like laquinimod will hope to match or better on safety, efficacy or convenience. So far laquinimod is also a once-daily, as is teriflunomide.
The latter of those two has reported phase III data, with additional analyses to be released at AAN (Sanofi details third promising oral MS therapy, October 18, 2010). A second trial is due next year, along with regulatory filings.
Little additional detail is expected at AAN on a third oral candidate, Biogen’s twice-daily BG-12. As two phase III trials, Define and Confirm, are expected to report data this year, observers are waiting for that event before judging its promise (Event - Biogen’s MS pill has high bar to cross, February 18, 2011).
The future oral MS landscape is not yet clear - detailed laquinimod data could help improve vision.