Alexion pays Achillion a $930m complement

A week after UCB bought Ra to get hold of its complement inhibitor, Alexion takes out Achillion for much the same reason.

Why stop at four complement inhibitors when you can have five? In buying Achillion for $930m up front Alexion has obtained the anti-complement factor D asset danicopan, yet another project in development for a complement-mediated disorder – in this case, paroxysmal nocturnal haemoglobinuria.

That is, assuming the deal gets past the FTC. Alexion already has so many complement-focused projects that the potential for interference on antitrust grounds is probably even higher than with last week’s UCB/Ra takeout, and going from four complement players to two in such a short time might draw the regulator’s attention (UCB goes to Ra for a complementary approach, October 10, 2019).

Moreover, part of the latest deal’s rationale is surely to protect the erosion of Soliris and Ultomiris’s sales from biosimilar competition, through combination with at least one of Achillion’s candidates.

Combining

The all-cash deal nets Alexion its first oral candidate for a complement-mediated disorder. Speaking on a conference call today, Alexion’s head of R&D, John Orloff, said the oral nature of danicopan, previously called ACH-4471, was “clearly an advantage over long subcutaneous infusions”.

The project is in phase II trials for PNH, and as such will become the next most advanced of Alexion’s complement pathway assets, behind the marketed injectables Soliris and Ultomiris.

Alexion's post-merger complement-mediated disease pipeline
Project Note Mechanism Delivery Status 2024e sales ($m)
Soliris - Anti-complement factor C5 MAb IV Sold for PNH, HUS & MG 3,402
Ultomiris - Anti-complement factor C5 MAb IV, working on SC Sold for PNH, filed for HUS, ph3 MG 2,470
ACH-4471/
danicopan
Acquired from Achillion Anti-complement factor D Oral Ph2 PNH & C3G 69
Synt001/
ALXN1830
Acquired from Syntimmune Anti-FcRn MAb IV, SC planned Ph2 MG -
ACH-5228 Acquired from Achillion Anti-complement factor D Oral Ph1 PNH 83
ACH-5548 Acquired from Achillion Anti-complement factor D Oral Ph1 COAD/COPD -
ABY-039 Licensed from Affibody Anti-FcRn bivalent
Ab mimetic
SC Ph1 -
Source: EvaluatePharma. PNH=paroxysmal nocturnal haemoglobinuria; HUS=haemolytic uremic syndrome; C3G=C3 glomuleropathy; MG=myasthenia gravis; COAD=chronic obstructive airways disease; COPD=chronic obstructive pulmonary disease.

The two groups were already linked. Danicopan’s ongoing phase II trial is investigating its use as an add-on to Soliris in PNH patients – particularly those who also have clinical extravascular haemolysis (EVH). 

Mr Orloff said that data so far were "very encouraging that we can get nice increases in haemoglobin in patients that have anaemia despite treatment with a C5 inhibitor”. Full results from this trial are expected by the end of the year, with regulatory discussions for the combo to begin immediately thereafter. 

All change

As for the rest of its newly acquired pipeline, Alexion believes that Achillion’s second most advanced factor D inhibitor, ACH-5228, might be a best-in-class complement inhibitor – and indeed this has higher sales forecasts, according to EvaluatePharma’s sellside consensus, than does danicopan.

Phase II trials of ACH-5228 in PNH are planned for the first half of next year, and the patients already enrolled in Achillion’s follow-on study of danicopan monotherapy in PNH will be converted to treatment with ’5228, which is also orally dosed.

For all of Alexion’s plans, the deal is almost as interesting for the story it tells about Achillion. The group was once a specialist in hepatitis C with a market cap in excess of $1.5bn, but switched focus after Gilead’s runaway success in hep C made it impossible to compete. 

Achillion investors will now receive $6.30 per share, a 73% premium to yesterday’s close. The stock is trading slightly above this price, possibly because management dodged a question on the call about the possibility of a higher counterbid.

Still, the takeout price remains a dismal showing for anyone who had kept faith with Achillion since its early 2015 peak of $15.99.

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