Having built a solid cardiopulmonary franchise the cash-rich Swiss company Actelion needs to branch out, and its latest target is autoimmune disorders, with plans to move the oral multiple sclerosis agent ponesimod into phase III as a successor to Novartis’s Gilenya.
But, though the planned study sets a low bar for success, it is important to note that Novartis has not been alone in this space for some time now. Indeed, Actelion’s unveiling of its plan yesterday coincided with a flurry of activity in multiple sclerosis and immunology that should make this area even more competitive.
Perhaps the biggest development was the granting, at long last, of US approval to Momenta’s generic version of Teva’s Copaxone (After seven years will Momenta and Sandoz wait any longer?, April 17, 2015). This will put pressure on pricing, though the oral space should remain immune for a while.
It is the oral treatment of MS that Actelion is targeting with ponesimod, mirroring Novartis’s Gilenya, a marketed MS drug with the same mechanism of action – S1P modulation. Actelion’s phase III Optimum trial will shortly start enrolling 1,100 relapsing MS patients with what the group calls a new titration schedule.
However, the comparator is not Gilenya, and certainly not the mightiest entrant to enter the oral space, Biogen’s Tecfidera. Instead it is Sanofi’s Aubagio, a drug that is not forecast to set the market on fire.
On a call yesterday Actelion’s chief executive, Jean-Paul Clozel, defended this decision, saying that demonstrating superiority versus either Gilenya or Tecfidera “would not be a reasonable target”, and would necessitate too big a study to detect a small effect. He also claimed that Aubagio was the “best and most active” comparator.
Cynics will of course draw a different conclusion, namely that Actelion has given itself an easy target to beat. The group’s plan to differentiate ponesimod centres on the titration schedule, which it hopes will avoid Gilenya’s so-called first-dose effect on heart rate, which necessitates patient monitoring.
None of this detracts from Actelion’s pursuit of an indication that has seen significant advances of late, especially when investors are rewarding even ambiguous early data, like that on Biogen’s anti-Lingo MAb BIIB033.
And just today Biogen bulls were reminded that these developments have brought with them competition: a practically unknown private French biotech, MedDay Pharmaceuticals, said a phase III trial of its lead asset, MD1003, had met the primary endpoint of improving expanded disability status scale or walking time in the tough indication of primary progressive MS.
MedDay says it will present detailed data at The American Academy of Neurology meeting on April 24, but its biggest problem is that MD1033 is basically a highly concentrated form of the food additive vitamin H. The group cites allowed US and Europe patents for MD1033’s dose and use, but concerns over the strength of this IP could deter partners.
For Actelion competition is even closer to home: look no further than the relatively crowded pipeline of projects targeting S1P modulation, including a second Novartis project and assets from Receptos, Merck KGaA and Mitsubishi Tanabe. Actelion itself has a ponesimod follow-up that could allow once-daily dosing and obviate titration, and is moving this into phase II for lupus.
The Receptos agent, ozanimod (RPC1063), is especially worth watching. Phase II data released last year showed reductions in brain lesion activity while minimising heart rate effects, suggesting the possibility of earlier treatment and stealing a march on Gilenya.
And there is a separate problem for Actelion, namely the possible expiry of Gilenya patents in 2019, which would add to the pricing pressure on me-too products.
Receptos was up 6% yesterday on positive data from the maintenance period of the phase II Touchstone trial of ozanimod in ulcerative colitis, after initial results last October had analysts touting the project as a future best-in-class agent. If this is the case Celgene’s handing over of $710m for Nogra Pharma’s Crohn’s disease project mongersen (GED-0301) will be questioned.
There have already been rumours that armed with strong data Receptos might itself fall prey to a takeover, but the group instead completed a bumper $360m equity raise, bringing the cash it had raised last year alone to over $600m.
In MS Receptos completed enrolment in ozanimod’s phase III Radiance study two weeks ago, while a second trial, Sunbeam, continues enrolling. It is ozanimod that could ultimately give Actelion a far bigger headache than Gilenya.
|Selected MS studies|