Biogen’s play for an entry in what looks to be the next big multiple sclerosis class signals that the race is well and truly on. Its dominant position in this space meant that it surely needed to lock up an asset, and Mitsubushi Tanabe Pharma’s phase II project seems to fit the bill.
This could be good news for Arena Pharmaceuticals and Akaal Pharma, which both have early programmes testing this pathway and could be seen as potential partnership targets. Biogen’s decision to license in MT-1303 suggests that the MS leader is hedging its bets in sphingosine-1-phosphate (S1P) receptor modulation, unlike Celgene, which went all in with its $7.2bn takeout of Receptos.
Last one standing?
Biogen licensed MT-1303 outside Asia for $60m up front, $484m in milestones and undisclosed royalties. Mitsubishi retains the right to participate in global clinical trials and co-promote non-MS indications in the US.
The US biotech might have been persuaded by data from a 415-patient placebo-controlled phase II dosing trial called Momentum. The trial, results of which are to be presented at the World Congress of Neurology in November, showed that daily doses of 0.1mg, 0.2mg and 0.4mg significantly reduced the number of brain lesions among MS patients. The higher two doses had a significant effect on brain volume and the highest dose significantly reduced the annualised relapse rate.
Adverse events were well balanced, including, importantly, the cardiovascular side effects that have required patients taking Novartis’s Gilenya, the first S1P agent, to remain under observation for six hours after their first dose.
In announcing the deal Biogen did not say whether the phase II data were sufficient to move into phase III, committing only to a “rapid development programme” in MS.
If this were to succeed in the clinic it would help extend the lifecycle of Biogen’s mighty MS franchise, which dates back to 1996 with the premiere of Avonex. MS products accounted for nearly all of its sales in 2014.
As the oral drug Tecfidera showed signs of plateauing this summer, and all of its MS products disappointed, the group needed something to restore optimism in the durability of the franchise, and an S1P deal seems designed to do just that.
Few small biotechs left
With the Biogen-Mitsubishi partnership, nearly all of the agents acting on the S1P pathway have been claimed by companies with the resources to develop and commercialise them.
A race is on to be the first follow-up to Gilenya, albeit one in which Novartis is in a strong position (Receptos data signals growing competition for MS pills, June 10, 2014). Siponimod’s phase III trial should read out in mid to late 2016, although this will be in the secondary progressive form of the disease.
Through its takeout of Receptos, Celgene has the leading candidate in relapsing disease, ozanimod, with its pivotal trials due to report in 2017. Actelion put ponesimod into phase III this year, though against an admittedly weak target, Sanofi’s Aubagio, with trials due to read out in 2018 (As multiple sclerosis competition steps up, Actelion steps in, April 17, 2015).
Merck KGaA and Ono Pharmaceutical gave up on ceralifimod last year, leaving the Mitsubishi project the main candidate in phase II, and the most likely partnership target. Arena’s main interest in its S1P, APD334, is in ulcerative colitis, an area where there is less competition for this mechanism. It could be that the California group is hoping to strike a partnership before testing in multiple indications.
This leaves as the other main partnering candidate the privately held Australia-based based Akaal Pharma, which is focusing on this pathway in psoriasis and MS. The MS candidate is in preclinical study in anticipation of filing an investigational new drug application.
It took several years after the launch of Gilenya for the S1P pipeline to mature. With Biogen having what could be the final word in partnering, the game now is to wait for data to emerge between today and 2018.