Welcome to your weekly digest of approaching regulatory and clinical readouts. Verona Pharma has pulled off a phase II win with its COPD asset RPL554 once before, and now it has to do it again: if the results of a second study in January are positive they should form the basis for pivotal work.
Perhaps equally importantly, the readout might address some questions the last phase II trial left unanswered, including whether or not the project will work better as an add-on therapy.
The more the merrier
The 70-patient study of RPL554, a PDE3/4 inhibitor, has a three-way crossover design testing two nebulised doses as an add-on to Respimat, versus placebo and Respimat alone. The primary outcome is the improvement in peak FEV1 on day three.
If the trial is successful, the next step is a dose-finding study – there had been previous concerns about a lack of dose-response – followed by phase III. This would be the natural entry point for any partner wishing to license RPL554, as it is unlikely that Verona would be able to fund the large-scale COPD trials required for registration.
Finding a partner might not be easy: even if the upcoming data are positive RPL554’s composition of matter patent is due to expire in 2020, before the expected COPD launch in 2021.
And RPL554 is the only candidate in Verona's pipeline. Much of the company’s development efforts are being spent expanding the project's use, including work on dry-powder and pressurised metered-dose inhalers. Trials of both are expected to start by late 2019.
Verona is also studying RPL554 in cystic fibrosis, but so far only in pharmacokinetic studies. Eventually work here could offer up US orphan drug status, extending exclusivity out another seven years, while slightly more mundane salts, combinations and formulations patents could push out the patent life until the 2030s.
But for now Verona has to hope that RPL554 will pass its next phase II test.
A new use for Ultomiris
Meanwhile, early next year Alexion will report data from a phase III open-label trial of its Soliris follow-on Ultomiris in its second indication, atypical haemolytic uremic syndrome (aHUS). The readout was previously expected in the fourth quarter of 2018, and investors will hope that the delay does not bode ill.
With Soliris’s US patent set to expire in 2027 Alexion has a lot is riding on switching patients to Ultomiris, whose main advantage is convenience. Both therapies are given intravenously, but Soliris is administered every two weeks, versus every eight weeks for the follow-on.
And in its lead indication, paroxysmal nocturnal haemoglobinuria (PNH), Ultomiris only managed to show non-inferiority, not superiority, to Soliris. Whether this will be enough for payers is another matter. Alexion has been tight-lipped about Ultomiris’s price, and investors will look for details if the project is approved by the US FDA, which is due to make a decision in PNH by February 18.
|Extending the franchise: Soliris vs Ultomiris|
Complicating this issue, Soliris's price varies across indications as it is dosed lower in PNH than aHUS; Ultomiris’s cost is expected to be fixed. Alexion therefore faces a balancing act: if it sets Ultomiris’s price at Soliris PNH levels it will be underpricing for aHUS in the future, but setting it higher could stop PNH patients switching.
The beginning of next year will also see several challenges to Alexion’s patents in Europe, in addition to future competition from subcutaneous inhibitors from Ra Pharmaceuticals, Roche and Regeneron (Ra joins the challenge to Alexion’s Soliris stranglehold, December 12, 2018).
Alexion is also developing a once-weekly subcutaneous formulation of Ultomiris, slated to enter phase III in late 2018.