Alexion hits endpoints in ALXN1210-Soliris test as it plots filings

Alexion hit key endpoints for its experimental phase 3 drug ALXN1210 in patients with a life-threatening ultrarare blood disorder.

The late-stage test was looking at whether this drug, a longer-acting follow-up of its superexpensive drug Soliris (eculizumab), was as good as Soliris as a first-line treatment for paroxysmal nocturnal hemoglobinuria (PNH).

Alexion says that the C5 complement inhibitor achieved noninferiority to its ultrarare disease marketed drug, also hitting its co-primary endpoints of transfusion avoidance and lactate dehydrogenase normalization, as well as all four secondary endpoints, all with similar safety levels to Soliris.

And as it hit noninferiority, the way it set up its test allowed it to see whether it could in fact top Soliris, using breakthrough hemolysis as the first endpoint for testing its potential superiority.

This didn’t pan out, but Alexion says: “Although ALXN1210 did not achieve superiority, a numeric trend in favor of ALXN1210 was observed for breakthrough hemolysis. The study also confirmed that ALXN1210 provides immediate and complete (>99%) inhibition of the complement C5 protein that is sustained over the entire 8-week dosing interval. Additionally, treatment with ALXN1210 reduced mean LDH levels to approximately the upper limit of normal … between months one and six.”

While not hitting superiority, this is still a broadly positive result for the biopharma, which says it now plans for regulatory submissions across the world starting in the coming months.  

John Orloff, M.D., EVP and head of R&D at Alexion, said: “We are very pleased with these positive data for ALXN1210 in the first and only head-to-head study versus Soliris, and the results reinforce our ambition to establish ALXN1210 as the new standard of care for patients with PNH. The data are also consistent with our hypothesis that immediate, complete, and sustained C5 inhibition is critical for patients with this potentially life-threatening disease. Soliris has established a high bar for efficacy. Achieving non-inferiority on both co-primary and all key secondary endpoints, as well as seeing numeric results in favor of ALXN1210, in such a rigorous study met a very high hurdle. We look forward to regulatory submissions of ALXN1210 in PNH in the U.S., EU, and Japan in the second half of 2018.”

ALXN1210 is also in late-stage trials for patients with PNH who have been treated with Soliris, as well as those with aHUS, another rare and life-threatening condition.

Analysts at Evercore said in a flash briefing this morning: “We believe these results are a win for ALXN. While some investors might push back that it leaves the door open for competitors, we don’t see any competitors well positioned as their development efforts are considerably slower (REGN, NVS) or their clinical profiles fall short of 1210 (Roche/Chugai due to immunogenicity, other agents). Furthermore, while stat sig was not reached [on some endpoints], some of the trends are rather compelling, particularly for breakthrough hemolysis and transfusion avoidance.”

Barclays analysts added: “The trial just missed showing superiority for 1210 based on better than expected performance in the Soliris control arm. The safety observations between the two medicines were indistinguishable and should alleviate any concerns about the liabilities of sustained complement inhibition with 1210.

“This [sic] data is consistent with our thesis that ALXN1210 will allow Alexion to extend the IP of their complement franchise from the mid- to late-2020s to 2035 and this should also mitigate many of the competitive concerns related to other complement inhibitors in development. We expect Alexion’s stock to react positively to this news and, we would be buyers of the stock even through $140-150/share.”

Alexion also has plans for a single, pharmacokinetics-based phase 3 of ALXN1210 delivered subcutaneously once per week as a potential treatment for patients with PNH and aHUS, and trials are also in the works for patients with generalized MG (gMG) and patients with immunoglobulin A nephropathy (IgAN).

Alexion was up around 6% premarket on the news.