Few companies have the timing and good fortune of Alexion Pharmaceuticals. It is not enough that the group can charge more than $600,000 a year for Soliris, a drug used by just 2,000 people, it also has managed to develop a follow-on that looks like it will keep the cash flowing well into the 2030s.
ALXN1210 does the same thing as Soliris with less frequent dosing, and phase III data revealed today show that the follow-on was equivalent on safety and efficacy. With competitors starting to nip at Alexion’s heels news that the Massachusetts-based group should be able to defend its franchise was taken well – shares rose 9% in early trading today.
Keep it flowing
With ALXN1210's eight-week maintenance dosing interval comparing favourably with infusions every two weeks for Soliris, Alexion did not really need to prove that the follow-on was better.
So the trial in paroxysmal nocturnal haemoglobinuria (PNH) simply showed that ALXN1210 was statistically non-inferior in keeping never-treated patients free of infusions and normalising lactate dehydrogenase (LDH). A test for superiority beginning with breakthrough haemolysis was unsuccessful, although ALXN1210 was better than Soliris numerically on all primary and secondary endpoints, the company said.
The trial results set Alexion up to submit the agent for regulatory approval later this year. Data from a Soliris-to-ALXN1210 switch study are due in the second quarter of 2018.
That latter trial will be equally important to proving that ALXN1210 can help sustain the franchise – with a PNH population numbering only about 1,000 in the US, converting patients from Soliris will be as important as attracting new ones who so far have been proven to respond.
As Stifel analyst Stephen Willey wrote, while ALXN1210 might not be a “meaningful longer-term accelerant of top-line growth”, it could extend the revenue stream for the PNH franchise if patients can switch. Soliris’s US patent falls in 2027, and ALXN1210 looks like it could go until 2035.
This should help address the looming threat of biosimilars – Amgen is among those developing a competitor – which could begin cutting into European sales as soon as 2020.
Moreover, novel competitors have entered in the complement inhibition space, with Akari and Ra talking of phase III trials of Coversin and RA101495 SC respectively later this year. Achillion has targeted the end of 2018 for interim data on ACH-4471 monotherapy, but is also looking at combinations with Soliris.
Among the complement inhibitors, little is known about Novartis and Morphosys’s tesidolumab and Roche’s RG6107 other than that phase II trials are listed as active at Clinicaltrials.gov.
|Alexion and its PNH rivals|
|Project||Company||2022 sales ($m)|
|Phase III||ALXN1210||Alexion Pharmaceuticals||423|
|Phase II||RA101495 SC||Ra Pharmaceuticals||88|
Alnylam's candidate cemdisiran is unique in a late-stage pipeline full of monoclonal antibodies, being an RNAi agent. The company appears to have greater hopes for this project in atypical haemolytic uraemic syndrome, another rare condition in which Soliris is used.
But with ALXN1210 now well ahead, and with Alexion’s well-known sales, marketing and medical affairs teams to support it, these rivals will have a tough time breaking through. Price competition is a possibility, but it would take an equally effective agent supported by an equally strong sales force – and that could be a very tall order.