A phase 3 trial of Alexion’s Soliris successor ALXN1210 has met its primary and key secondary endpoints. The success positions Alexion to file for approval and shield itself from an anticipated assault on its cash cow paroxysmal nocturnal hemoglobinuria (PNH) franchise.
ALXN1210, like Soliris, is a C5 complement inhibitor designed to stop the destruction of red blood cells and thereby prevent PNH causing clots and organ damage. The critical difference is ALXN1210 is a long-acting formulation administered every eight weeks. Patients on Soliris receive infusions of the drug every two weeks.
Seeking to protect its franchise through a less onerous dosing schedule, Alexion tested the effect of switching 195 PNH patients from Soliris to ALXN1210. The data support moving patients to the long-acting product.
Investigators enrolled 195 adults with PNH in the open-label trial and randomized them to either stay on Soliris or switch to ALXN1210. After 26 weeks of treatment, there was no statistically significant difference between the changes in lactate dehydrogenase levels (LDH) across the two arms, resulting in the trial hitting its primary endpoint. The study linked ALXN1210 to changes in LDH levels that fell just shy of statistical superiority over Soliris.
A similar pattern was seen across four key secondary endpoints. ALXN1210 performed numerically better than Soliris against each measure and, as such, met the goal of noninferiority. The occurrence of five cases of breakthrough hemolysis in the Soliris arm, compared to none in the ALXN1210, further bolstered the case that the new drug is at least as good as its predecessor.
Clearing the bar of statistical superiority would have been the cherry on top. But Alexion CEO Ludwig Hantson thinks the overall data package is nonetheless strong enough for ALXN1210 to win over regulators and then hit the ground running when it comes to market.
“The way I look at it, we don't need the superiority claim to be successful for a fast conversion. We have a strong, differentiated clinical profile, a robust data package,” Hantson said on a conference call with investors.
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Alexion plans to take data from the phase 3 and results from prior study in treatment-naïve patients to regulators soon, starting with filings in the U.S. and Europe around the middle of the year.
That would give Alexion a decent window to switch patients over to ALXN1210 before the arrival of biosimilar copies of Soliris or rival innovative drugs upsets its dominance of PNH. Amgen is among the companies working on biosimilar versions of Soliris, while a clutch of R&D shops including Alnylam, Novartis and Roche are developing novel PNH candidates.
The success of ALXN1210 suggests Alexion may have the best PNH drug on the market even after the approval of competitors, but with payers keen to knock down the hefty price charged by Alexion, the availability of drugs that match Soliris could still disrupt its business.
“Notwithstanding ALXN1210 Ph3 success, we continue to see likely active pricing pressure/market share loss, if competitor product(s) are approved in >~2021, particularly in ex-U.S. markets,” analysts at Jefferies wrote in a note to investors.